Immunoglobulin therapy: Difference between revisions
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{{Short description|Medical treatment}} |
{{Short description|Medical treatment}} |
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{{Split|normal human immunoglobulin|discuss=Talk:Immunoglobulin therapy#Split|date=December 2020}} |
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| Drugs.com = {{Drugs.com|monograph|immune-globulin}} |
| Drugs.com = {{Drugs.com|monograph|immune-globulin}} |
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| routes_of_administration = [[Intravenous therapy|Intravenous]], [[Intramuscular injection|intramuscular]], [[Subcutaneous injection|subcutaneous]] |
| routes_of_administration = [[Intravenous therapy|Intravenous]], [[Intramuscular injection|intramuscular]], [[Subcutaneous injection|subcutaneous]] |
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| legal_CA = Rx-only |
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| legal_CA_comment = <ref>{{cite web | title=Regulatory Decision Summary - Xembify | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00596 | access-date=7 June 2022 | archive-date=7 June 2022 | archive-url=https://web.archive.org/web/20220607034842/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00596 | url-status=live }}</ref><ref>{{cite web | title=Summary Basis of Decision - HyQvia | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00592&lang=en | access-date=6 August 2022}}</ref> |
| legal_CA_comment = <ref>{{cite web | title=Regulatory Decision Summary - Xembify | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00596 | access-date=7 June 2022 | archive-date=7 June 2022 | archive-url=https://web.archive.org/web/20220607034842/https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?lang=en&linkID=RDS00596 | url-status=live }}</ref><ref>{{cite web | title=Summary Basis of Decision - HyQvia | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00592&lang=en | access-date=6 August 2022}}</ref><ref>{{cite web | title=Immune system health | website=[[Health Canada]] | date=9 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/immune-system-health.html | access-date=13 April 2024}}</ref><ref>{{cite web | title=Drug and medical device highlights 2018: Helping you maintain and improve your health | website=[[Health Canada]] | date=14 October 2020 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/drug-medical-device-highlights-2018.html | access-date=17 April 2024}}</ref> |
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| legal_US_comment = <ref name="Asceniv FDA label" /><ref name="Bivigam FDA label" /><ref name="Gamunex-C FDA label" /><ref name="Alyglo FDA label" /> |
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<!-- Identifiers --> |
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| CAS_number = 9007-83-4 |
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<!-- Definition and medical uses --> |
<!-- Definition and medical uses --> |
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'''Immunoglobulin therapy''' is the use of a mixture of [[antibodies]] ( |
'''Immunoglobulin therapy''' is the use of a mixture of [[antibodies]] (normal human immunoglobulin) to treat several health conditions.<ref name=AHFS2017/><ref name=BNF69>{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|pages=867–71|edition=69}}</ref> These conditions include [[primary immunodeficiency]], [[immune thrombocytopenic purpura]], [[chronic inflammatory demyelinating polyneuropathy]], [[Kawasaki disease]], certain cases of [[HIV/AIDS]] and [[measles]], [[Guillain–Barré syndrome]], and certain other infections when a more specific immunoglobulin is not available.<ref name=AHFS2017/> Depending on the formulation it can be given by [[injection into muscle]], a [[intravenous|vein]], or [[subcutaneous injection|under the skin]].<ref name=AHFS2017>{{cite web|title=Immune Globulin|url=https://www.drugs.com/monograph/immune-globulin.html|publisher=The American Society of Health-System Pharmacists|access-date=8 January 2017|url-status=live|archive-url=https://web.archive.org/web/20170109190342/https://www.drugs.com/monograph/immune-globulin.html|archive-date=9 January 2017}}</ref> The effects last a few weeks.<ref name=BNF69/> |
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== Medical uses == |
== Medical uses == |
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Immunoglobulin therapy is used in a variety of conditions, many of which involve decreased or abolished antibody production capabilities, which range from a complete absence of multiple types of antibodies, to [[IgG deficiency|IgG subclass deficiencies]] (usually involving IgG2 or IgG3), to other disorders in which antibodies are within a normal quantitative range, but lacking in quality – unable to respond to antigens as they normally should – resulting in an increased rate or increased severity of infections. In these situations, immunoglobulin infusions confer passive resistance to infection on their recipients by increasing the quantity/quality of [[Immunoglobulin G|IgG]] they possess. Immunoglobulin therapy is also used for a number of other conditions, including in many autoimmune disorders such as [[dermatomyositis]] in an attempt to decrease the severity of symptoms. Immunoglobulin therapy is also used in some treatment protocols for [[Immunosuppression|secondary immunodeficiencies]] <!-- not an ideal link target --> such as [[human immunodeficiency virus]] (HIV), some autoimmune disorders (such as [[immune thrombocytopenia]] and [[Kawasaki disease]]), some neurological diseases ([[multifocal motor neuropathy]], [[stiff person syndrome]], [[multiple sclerosis]] and [[myasthenia gravis]]) some acute infections and some complications of organ transplantation.<ref name="aireview">{{cite journal | vauthors = Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson RP, Patel DD, Secord E, Sorensen RU, Wasserman RL, Cunningham-Rundles C |
Immunoglobulin therapy is used in a variety of conditions, many of which involve decreased or abolished antibody production capabilities, which range from a complete absence of multiple types of antibodies, to [[IgG deficiency|IgG subclass deficiencies]] (usually involving IgG2 or IgG3), to other disorders in which antibodies are within a normal quantitative range, but lacking in quality – unable to respond to antigens as they normally should – resulting in an increased rate or increased severity of infections. In these situations, immunoglobulin infusions confer passive resistance to infection on their recipients by increasing the quantity/quality of [[Immunoglobulin G|IgG]] they possess. Immunoglobulin therapy is also used for a number of other conditions, including in many autoimmune disorders such as [[dermatomyositis]] in an attempt to decrease the severity of symptoms. Immunoglobulin therapy is also used in some treatment protocols for [[Immunosuppression|secondary immunodeficiencies]] <!-- not an ideal link target --> such as [[human immunodeficiency virus]] (HIV), some autoimmune disorders (such as [[immune thrombocytopenia]] and [[Kawasaki disease]]), some neurological diseases ([[multifocal motor neuropathy]], [[stiff person syndrome]], [[multiple sclerosis]] and [[myasthenia gravis]]) some acute infections and some complications of organ transplantation.<ref name="aireview">{{cite journal | vauthors = Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson RP, Patel DD, Secord E, Sorensen RU, Wasserman RL, Cunningham-Rundles C | title = Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology | journal = The Journal of Allergy and Clinical Immunology | volume = 117 | issue = 4 Suppl | pages = S525–S553 | date = April 2006 | pmid = 16580469 | doi = 10.1016/j.jaci.2006.01.015 | type = Review | doi-access = free | title-link = doi }}</ref> |
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Immunoglobulin therapy is especially useful in some acute infection cases such as [[pediatry|pediatric]] [[HIV]] infection and is also considered the standard of treatment for some autoimmune disorders such as [[Guillain–Barré syndrome]].<ref name=gbs>{{cite journal | vauthors = van Doorn PA, Kuitwaard K, Walgaard C, van Koningsveld R, Ruts L, Jacobs BC | title = IVIG treatment and prognosis in Guillain-Barré syndrome | journal = Journal of Clinical Immunology | volume = 30 | issue = S1 | pages = S74–S78 | date = May 2010 | pmid = 20396937 | pmc = 2883091 | doi = 10.1007/s10875-010-9407-4 }}</ref><ref name="gbs2">{{cite journal | vauthors = Hughes RA, Wijdicks EF, Barohn R, Benson E, Cornblath DR, Hahn AF, Meythaler JM, Miller RG, Sladky JT, Stevens JC |
Immunoglobulin therapy is especially useful in some acute infection cases such as [[pediatry|pediatric]] [[HIV]] infection and is also considered the standard of treatment for some autoimmune disorders such as [[Guillain–Barré syndrome]].<ref name=gbs>{{cite journal | vauthors = van Doorn PA, Kuitwaard K, Walgaard C, van Koningsveld R, Ruts L, Jacobs BC | title = IVIG treatment and prognosis in Guillain-Barré syndrome | journal = Journal of Clinical Immunology | volume = 30 | issue = S1 | pages = S74–S78 | date = May 2010 | pmid = 20396937 | pmc = 2883091 | doi = 10.1007/s10875-010-9407-4 }}</ref><ref name="gbs2">{{cite journal | vauthors = Hughes RA, Wijdicks EF, Barohn R, Benson E, Cornblath DR, Hahn AF, Meythaler JM, Miller RG, Sladky JT, Stevens JC | title = Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 61 | issue = 6 | pages = 736–740 | date = September 2003 | pmid = 14504313 | doi = 10.1212/WNL.61.6.736 | s2cid = 20577426 | doi-access = free | title-link = doi }}</ref> The high demand which coupled with the difficulty of producing immunoglobulin in large quantities has resulted in increasing global shortages, usage limitations and rationing of immunoglobulin.<ref name="shortage">{{cite journal | vauthors = Pondrom S | title = The IVIg dilemma | journal = American Journal of Transplantation | volume = 14 | issue = 10 | pages = 2195–2196 | date = October 2014 | pmid = 25231064 | doi = 10.1111/ajt.12995 | s2cid = 221433035 | department = The AJT Report | doi-access = free | title-link = doi }}</ref> |
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⚫ | The United Kingdom's [[National Health Service]] recommends the routine use of immunoglobulin for a variety of conditions including primary immunodeficiencies and a number of other conditions, but recommends against the use of immunoglobulin in [[sepsis]] (unless a specific toxin has been identified), multiple sclerosis, neonatal sepsis, and pediatric [[HIV/AIDS]].<ref name=NHS>{{cite web|title=Clinical Guidelines for Immunoglobulin Use|url=http://www.ivig.nhs.uk/documents/dh_129666.pdf|website=National Health Service|access-date=5 December 2015|url-status=live|archive-url=https://web.archive.org/web/20150529042116/http://www.ivig.nhs.uk/documents/dh_129666.pdf|archive-date=29 May 2015}}</ref> |
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⚫ | The [[American Academy of Allergy, Asthma, and Immunology]] supports the use of [[immunoglobulin]] for primary immunodeficiencies, while noting that such usage actually accounts for a minority of usage and acknowledging that immunoglobulin supplementation can be appropriately used for a number of other conditions,<ref name=aaai1>{{cite web|title=Eight guiding principals for safe, effective and appropriate use of IVIG|url=https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|publisher=American Association of Allergists and Immunologists|access-date=5 December 2015|url-status=live|archive-url=https://web.archive.org/web/20160305025940/https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|archive-date=5 March 2016}}</ref> including neonatal sepsis (citing a sixfold decrease in mortality), considered in cases of HIV (including pediatric HIV), considered as a second line treatment in relapsing-remitting multiple sclerosis, but recommending against its use in such conditions as [[chronic fatigue syndrome]], [[PANDAS]] (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) until further evidence to support its use is found (though noting that it may be useful in PANDAS patients with an autoimmune component), cystic fibrosis, and a number of other conditions.<ref name="aireview" /> |
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⚫ | * Asceniv (immune globulin intravenous, human – slra)<ref>{{cite web | title=Asceniv – human immunoglobulin g liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d74f4360-3b51-496c-96fb-84c3976958d2 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173255/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d74f4360-3b51-496c-96fb-84c3976958d2 | url-status=live }}</ref> |
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⚫ | * Bivigam (immune globulin intravenous – human 10% liquid)<ref>{{cite web | title=Bivigam (immune globulin intravenous – human 10% liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2244aa0-a6d0-11df-b385-0002a5d5c51b | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173253/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2244aa0-a6d0-11df-b385-0002a5d5c51b | url-status=live }}</ref> |
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⚫ | * Gamunex-C, (immune globulin injection human)<ref>{{cite web | title=Gamunex-C (immune globulin – human injection | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ade6b84a-e95b-0a49-3296-f56208fdf35b | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173254/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ade6b84a-e95b-0a49-3296-f56208fdf35b | url-status=live }}</ref> |
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⚫ | * Hizentra (immune globulin subcutaneous human)<ref>{{cite web | title=Hizentra – human immunoglobulin g liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b58f5ff-0316-49a3-b585-1f6003ddb953 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173252/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b58f5ff-0316-49a3-b585-1f6003ddb953 | url-status=live }}</ref> |
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⚫ | * Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase)<ref>{{cite web | title=Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | access-date=9 June 2021 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805002533/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | url-status=live }}</ref> |
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* Octagam (immune globulin intravenous, human)<ref>{{cite web | title=Octagam immune globulin (human) – immune globulin solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de00abeb-d635-eddc-b603-10708ecef5aa | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173301/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de00abeb-d635-eddc-b603-10708ecef5aa | url-status=live }}</ref><ref>{{cite web | title=Octagam immune globulin (human) – immune globulin solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a36a12dc-16be-b135-466f-393954f428a7 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173259/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a36a12dc-16be-b135-466f-393954f428a7 | url-status=live }}</ref> |
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⚫ | * Panzyga (immune globulin intravenous, human – ifas)<ref>{{cite web | title=Panzyga (immune globulin intravenous – human solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68a5ee5f-0352-b3ae-3321-c0a22947a31d | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173303/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68a5ee5f-0352-b3ae-3321-c0a22947a31d | url-status=live }}</ref> |
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⚫ | * Xembify (immune globulin subcutaneous, human – klhw)<ref>{{cite web | title=Xembify – immune globulin subcutaneous, human-klhw solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c174b11-a061-412e-a3b2-7bf7e1adaace | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173304/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c174b11-a061-412e-a3b2-7bf7e1adaace | url-status=live }}</ref> |
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⚫ | The National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services have also developed their own separate set of guidelines for the appropriate use of immunoglobulin therapy, which strongly support the use of immunoglobulin therapy in primary immunodeficiencies and some complications of HIV, while remaining silent on the issues of sepsis, multiple sclerosis, and chronic fatigue syndrome.<ref name="canada">{{cite journal | vauthors = Anderson D, Ali K, Blanchette V, Brouwers M, Couban S, Radmoor P, Huebsch L, Hume H, McLeod A, Meyer R, Moltzan C, Nahirniak S, Nantel S, Pineo G, Rock G |
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===Australia=== |
===Australia=== |
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Human normal immunoglobulin (human immunoglobulin G) (Cutaquig) was approved for medical use in Australia in May 2021.<ref name="Cutaquig APM summary">{{cite web | title=Cutaquig | website=Therapeutic Goods Administration (TGA) | date=12 May 2021 | url=https://www.tga.gov.au/apm-summary/cutaquig | access-date=6 September 2021 | archive-date=6 September 2021 | archive-url=https://web.archive.org/web/20210906213353/https://www.tga.gov.au/apm-summary/cutaquig | url-status=live }}</ref> |
Human normal immunoglobulin (human immunoglobulin G) (Cutaquig) was approved for medical use in Australia in May 2021.<ref name="Cutaquig APM summary">{{cite web | title=Cutaquig | website=Therapeutic Goods Administration (TGA) | date=12 May 2021 | url=https://www.tga.gov.au/apm-summary/cutaquig | access-date=6 September 2021 | archive-date=6 September 2021 | archive-url=https://web.archive.org/web/20210906213353/https://www.tga.gov.au/apm-summary/cutaquig | url-status=live }}</ref> |
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⚫ | The National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services have also developed their own separate set of guidelines for the appropriate use of immunoglobulin therapy, which strongly support the use of immunoglobulin therapy in primary immunodeficiencies and some complications of HIV, while remaining silent on the issues of sepsis, multiple sclerosis, and chronic fatigue syndrome.<ref name="canada">{{cite journal | vauthors = Anderson D, Ali K, Blanchette V, Brouwers M, Couban S, Radmoor P, Huebsch L, Hume H, McLeod A, Meyer R, Moltzan C, Nahirniak S, Nantel S, Pineo G, Rock G | title = Guidelines on the use of intravenous immune globulin for hematologic conditions | journal = Transfusion Medicine Reviews | volume = 21 | issue = 2 Suppl 1 | pages = S9-56 | date = April 2007 | pmid = 17397769 | doi = 10.1016/j.tmrv.2007.01.001 }}</ref> |
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=== European Union === |
=== European Union === |
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Brands include HyQvia (human normal immunoglobulin), Privigen (human normal immunoglobulin (IVIg)), Hizentra (human normal immunoglobulin (SCIg)), Kiovig (human normal immunoglobulin), and Flebogamma DIF (human normal immunoglobulin).<ref name="HyQvia EPAR">{{cite web | title=HyQvia EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia | access-date=14 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715021548/https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia | url-status=live }}</ref><ref name="Hizentra EPAR" /><ref name="Privigen EPAR">{{cite web | title=Privigen EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/privigen | access-date=14 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715021009/https://www.ema.europa.eu/en/medicines/human/EPAR/privigen | url-status=live }}</ref><ref name="Kiovig EPAR">{{cite web | title=Kiovig EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kiovig | access-date=14 July 2020 | archive-date=17 July 2020 | archive-url=https://web.archive.org/web/20200717013809/https://www.ema.europa.eu/en/medicines/human/EPAR/kiovig | url-status=live }}</ref> |
Brands include HyQvia (human normal immunoglobulin), Privigen (human normal immunoglobulin (IVIg)), Hizentra (human normal immunoglobulin (SCIg)), Kiovig (human normal immunoglobulin), and Flebogamma DIF (human normal immunoglobulin).<ref name="HyQvia EPAR">{{cite web | title=HyQvia EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia | access-date=14 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715021548/https://www.ema.europa.eu/en/medicines/human/EPAR/hyqvia | url-status=live }}</ref><ref name="Hizentra EPAR" /><ref name="Privigen EPAR">{{cite web | title=Privigen EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/privigen | access-date=14 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715021009/https://www.ema.europa.eu/en/medicines/human/EPAR/privigen | url-status=live }}</ref><ref name="Kiovig EPAR">{{cite web | title=Kiovig EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/kiovig | access-date=14 July 2020 | archive-date=17 July 2020 | archive-url=https://web.archive.org/web/20200717013809/https://www.ema.europa.eu/en/medicines/human/EPAR/kiovig | url-status=live }}</ref> |
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In the EU human normal immunoglobulin (SCIg) (Hizentra) is used in people whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins.<ref name="Hizentra EPAR">{{cite web | title=Hizentra EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/hizentra | access-date=2 May 2020 | archive-date=1 August 2020 | archive-url=https://web.archive.org/web/20200801233153/https://www.ema.europa.eu/en/medicines/human/EPAR/hizentra | url-status=live }} Text was copied from this source which is |
In the EU human normal immunoglobulin (SCIg) (Hizentra) is used in people whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins.<ref name="Hizentra EPAR">{{cite web | title=Hizentra EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/hizentra | access-date=2 May 2020 | archive-date=1 August 2020 | archive-url=https://web.archive.org/web/20200801233153/https://www.ema.europa.eu/en/medicines/human/EPAR/hizentra | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> It is used to treat the following conditions: |
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* primary immunodeficiency syndromes (PID, when people are born with an inability to produce enough antibodies);<ref name="Hizentra EPAR" /> |
* primary immunodeficiency syndromes (PID, when people are born with an inability to produce enough antibodies);<ref name="Hizentra EPAR" /> |
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* low levels of antibodies in the blood in people with chronic lymphocytic leukaemia (a cancer of a type of white blood cell) or myeloma (a cancer of another type of white blood cell) and who have frequent infections;<ref name="Hizentra EPAR" /> |
* low levels of antibodies in the blood in people with chronic lymphocytic leukaemia (a cancer of a type of white blood cell) or myeloma (a cancer of another type of white blood cell) and who have frequent infections;<ref name="Hizentra EPAR" /> |
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It is indicated for replacement therapy in adults and children in primary immunodeficiency syndromes such as: |
It is indicated for replacement therapy in adults and children in primary immunodeficiency syndromes such as: |
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* congenital agammaglobulinaemia and hypogammaglobulinaemia (low levels of antibodies);<ref name="Hizentra EPAR" /> |
* congenital agammaglobulinaemia and hypogammaglobulinaemia (low levels of antibodies);<ref name="Hizentra EPAR" /> |
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* common variable immunodeficiency;<ref name="Hizentra EPAR" /> |
* common variable immunodeficiency;<ref name="Hizentra EPAR" /> |
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Line 162: | Line 135: | ||
Flebogamma DIF is indicated for the replacement therapy in adults, children and adolescents (0–18 years) in: |
Flebogamma DIF is indicated for the replacement therapy in adults, children and adolescents (0–18 years) in: |
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* primary immunodeficiency syndromes with impaired antibody production;<ref name="Flebogamma DIF">{{cite web | title=Flebogamma DIF | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/flebogamma-dif | access-date=15 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715105531/https://www.ema.europa.eu/en/medicines/human/EPAR/flebogamma-dif | url-status=live }} Text was copied from this source which is |
* primary immunodeficiency syndromes with impaired antibody production;<ref name="Flebogamma DIF">{{cite web | title=Flebogamma DIF | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/flebogamma-dif | access-date=15 July 2020 | archive-date=15 July 2020 | archive-url=https://web.archive.org/web/20200715105531/https://www.ema.europa.eu/en/medicines/human/EPAR/flebogamma-dif | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> |
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* hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (a cancer of a type of white blood cell), in whom prophylactic antibiotics have failed;<ref name="Flebogamma DIF" /> |
* hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (a cancer of a type of white blood cell), in whom prophylactic antibiotics have failed;<ref name="Flebogamma DIF" /> |
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* hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in plateau-phase-multiple-myeloma (another cancer of a type of white blood cell) patients who failed to respond to pneumococcal immunisation;<ref name="Flebogamma DIF" /> |
* hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in plateau-phase-multiple-myeloma (another cancer of a type of white blood cell) patients who failed to respond to pneumococcal immunisation;<ref name="Flebogamma DIF" /> |
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and for the immunomodulation in adults, children and adolescents (0–18 years) in: |
and for the immunomodulation in adults, children and adolescents (0–18 years) in: |
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* primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count;<ref name="Flebogamma DIF" /> |
* primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count;<ref name="Flebogamma DIF" /> |
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* Guillain–Barré syndrome, which causes multiple inflammations of the nerves in the body;<ref name="Flebogamma DIF" /> |
* Guillain–Barré syndrome, which causes multiple inflammations of the nerves in the body;<ref name="Flebogamma DIF" /> |
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* Kawasaki disease, which causes multiple inflammation of several organs in the body.<ref name="Flebogamma DIF" /> |
* Kawasaki disease, which causes multiple inflammation of several organs in the body.<ref name="Flebogamma DIF" /> |
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⚫ | |||
⚫ | The United Kingdom's [[National Health Service]] recommends the routine use of immunoglobulin for a variety of conditions including primary immunodeficiencies and a number of other conditions, but recommends against the use of immunoglobulin in [[sepsis]] (unless a specific toxin has been identified), multiple sclerosis, neonatal sepsis, and pediatric [[HIV/AIDS]].<ref name=NHS>{{cite web|title=Clinical Guidelines for Immunoglobulin Use|url=http://www.ivig.nhs.uk/documents/dh_129666.pdf|website=National Health Service|access-date=5 December 2015|url-status=live|archive-url=https://web.archive.org/web/20150529042116/http://www.ivig.nhs.uk/documents/dh_129666.pdf|archive-date=29 May 2015}}</ref> |
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⚫ | |||
⚫ | The [[American Academy of Allergy, Asthma, and Immunology]] supports the use of [[immunoglobulin]] for primary immunodeficiencies, while noting that such usage actually accounts for a minority of usage and acknowledging that immunoglobulin supplementation can be appropriately used for a number of other conditions,<ref name=aaai1>{{cite web|title=Eight guiding principals for safe, effective and appropriate use of IVIG|url=https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|publisher=American Association of Allergists and Immunologists|access-date=5 December 2015|url-status=live|archive-url=https://web.archive.org/web/20160305025940/https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|archive-date=5 March 2016}}</ref> including neonatal sepsis (citing a sixfold decrease in mortality), considered in cases of HIV (including pediatric HIV), considered as a second line treatment in relapsing-remitting multiple sclerosis, but recommending against its use in such conditions as [[chronic fatigue syndrome]], [[PANDAS]] (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) until further evidence to support its use is found (though noting that it may be useful in PANDAS patients with an autoimmune component), cystic fibrosis, and a number of other conditions.<ref name="aireview" /> |
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⚫ | |||
* Alyglo (immune globulin intravenous human-stwk)<ref name="Alyglo FDA label">{{cite web | title=Alyglo- human immunoglobulin g liquid | website=DailyMed | date=15 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fb97b3ec-29ee-4df1-aa99-c23e57a21228 | access-date=3 March 2024}}</ref><ref name="FDA Alyglo">{{cite web | title=Alyglo | website=U.S. [[Food and Drug Administration]] (FDA) | date=15 December 2023 | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/alyglo | access-date=22 December 2023}}</ref> |
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⚫ | * Asceniv (immune globulin intravenous, human – slra)<ref name="Asceniv FDA label">{{cite web | title=Asceniv – human immunoglobulin g liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d74f4360-3b51-496c-96fb-84c3976958d2 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173255/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d74f4360-3b51-496c-96fb-84c3976958d2 | url-status=live }}</ref> |
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⚫ | * Bivigam (immune globulin intravenous – human 10% liquid)<ref name="Bivigam FDA label">{{cite web | title=Bivigam (immune globulin intravenous – human 10% liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2244aa0-a6d0-11df-b385-0002a5d5c51b | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173253/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2244aa0-a6d0-11df-b385-0002a5d5c51b | url-status=live }}</ref> |
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⚫ | * Gamunex-C, (immune globulin injection human)<ref name="Gamunex-C FDA label">{{cite web | title=Gamunex-C (immune globulin – human injection | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ade6b84a-e95b-0a49-3296-f56208fdf35b | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173254/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ade6b84a-e95b-0a49-3296-f56208fdf35b | url-status=live }}</ref> |
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⚫ | * Hizentra (immune globulin subcutaneous human)<ref name="Hizentra FDA label">{{cite web | title=Hizentra – human immunoglobulin g liquid | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b58f5ff-0316-49a3-b585-1f6003ddb953 | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173252/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b58f5ff-0316-49a3-b585-1f6003ddb953 | url-status=live }}</ref> |
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⚫ | * Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase)<ref name="Hyqvia FDA label">{{cite web | title=Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | access-date=9 June 2021 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805002533/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | url-status=live }}</ref> |
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* Octagam (immune globulin intravenous, human)<ref name="Octagam FDA label">{{cite web | title=Octagam immune globulin (human)- immune globulin solution | website=DailyMed | date=26 January 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eb4c342b-122c-0072-1428-1747882e6c00 | access-date=26 February 2024}}</ref> |
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⚫ | * Panzyga (immune globulin intravenous, human – ifas)<ref name="Panzyga FDA label">{{cite web | title=Panzyga (immune globulin intravenous – human solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68a5ee5f-0352-b3ae-3321-c0a22947a31d | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173303/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=68a5ee5f-0352-b3ae-3321-c0a22947a31d | url-status=live }}</ref> |
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⚫ | * Xembify (immune globulin subcutaneous, human – klhw)<ref name="Xembify FDA label">{{cite web | title=Xembify – immune globulin subcutaneous, human-klhw solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c174b11-a061-412e-a3b2-7bf7e1adaace | access-date=9 June 2021 | archive-date=9 June 2021 | archive-url=https://web.archive.org/web/20210609173304/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8c174b11-a061-412e-a3b2-7bf7e1adaace | url-status=live }}</ref> |
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== Side effects == |
== Side effects == |
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Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compared to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration). Patients who are receiving immunoglobulin and experience adverse events are sometimes recommended to take [[acetaminophen]] and [[diphenhydramine]] before their infusions to reduce the rate of adverse effects. Additional premedication may be required in some instances (especially when first getting accustomed to a new dosage), [[prednisone]] or another oral steroid.{{citation needed|date=December 2021}} |
Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compared to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration). Patients who are receiving immunoglobulin and experience adverse events are sometimes recommended to take [[acetaminophen]] and [[diphenhydramine]] before their infusions to reduce the rate of adverse effects. Additional premedication may be required in some instances (especially when first getting accustomed to a new dosage), [[prednisone]] or another oral steroid.{{citation needed|date=December 2021}} |
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Local side effects of immunoglobulin infusions most frequently include an injection site reaction (reddening of the skin around the injection site), itching, rash, and hives.<ref name=dyna>{{cite web|title=Immune Globulin|url=http://www.dynamed.com/topics/dmp~AN~T356495/Immune-Globulin#Contraindications-Warnings|website=Dynamed|access-date=23 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151208192710/http://www.dynamed.com/topics/dmp~AN~T356495/Immune-Globulin#Contraindications-Warnings|archive-date=8 December 2015|url-access=subscription}}{{Subscription or libraries|s}}</ref> Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.<ref name=dyna/> |
Local side effects of immunoglobulin infusions most frequently include an [[injection site reaction]] (reddening of the skin around the injection site), itching, rash, and hives.<ref name=dyna>{{cite web|title=Immune Globulin|url=http://www.dynamed.com/topics/dmp~AN~T356495/Immune-Globulin#Contraindications-Warnings|website=Dynamed|access-date=23 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151208192710/http://www.dynamed.com/topics/dmp~AN~T356495/Immune-Globulin#Contraindications-Warnings|archive-date=8 December 2015|url-access=subscription}}{{Subscription or libraries|s}}</ref> Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.<ref name=dyna/> |
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Serious side effects of immunoglobulin infusions include chest discomfort or pain, [[myocardial infarction]], [[tachycardia]], [[hyponatremia]], [[hemolysis]], [[hemolytic anemia]], [[thrombosis]], [[hepatitis]], [[anaphylaxis]], backache, [[aseptic meningitis]], [[acute kidney injury]], hypokalemic [[nephropathy]], [[pulmonary embolism]], and [[transfusion related acute lung injury]] |
Serious side effects of immunoglobulin infusions in infants, children,<ref>{{Cite web |date=2024-05-09 |title=Comparing Two Treatments for IVIG-Resistant Kawasaki Disease - Evidence Update for Clinicians {{!}} PCORI |url=https://www.pcori.org/evidence-updates/comparing-two-treatments-ivig-resistant-kawasaki-disease |access-date=2024-07-11 |website=www.pcori.org |language=en}}</ref> and adults include chest discomfort or pain, [[myocardial infarction]], [[tachycardia]], [[hyponatremia]], [[hemolysis]], [[hemolytic anemia]], [[thrombosis]], [[hepatitis]], [[anaphylaxis]], backache, [[aseptic meningitis]], [[acute kidney injury]], hypokalemic [[nephropathy]], [[pulmonary embolism]], and [[transfusion related acute lung injury|transfusion related acute lung injury.]]<ref name=dyna/> hemoThere is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient.<ref name=dyna/> Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.<ref>{{cite journal | vauthors = Daw Z, Padmore R, Neurath D, Cober N, Tokessy M, Desjardins D, Olberg B, Tinmouth A, Giulivi A | title = Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis | journal = Transfusion | volume = 48 | issue = 8 | pages = 1598–1601 | date = August 2008 | pmid = 18466176 | doi = 10.1111/j.1537-2995.2008.01721.x | s2cid = 6010463 }}</ref> |
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IVIG has long been known to induce a decrease in peripheral blood neutrophil count, or [[neutropenia]] in neonates,<ref>{{cite journal | vauthors = Lassiter HA, Bibb KW, Bertolone SJ, Patel CC, Stroncek DF | title = Neonatal immune neutropenia following the administration of intravenous immune globulin | journal = The American Journal of Pediatric Hematology/Oncology | volume = 15 | issue = 1 | pages = 120–123 | date = February 1993 | pmid = 8447553 | doi = 10.1097/00043426-199302000-00019 }}</ref> and in patients with [[Idiopathic Thrombocytopenic Purpura]], resolving spontaneously and without complications within 48 h.<ref>{{cite journal | vauthors = Sugita K, Eguchi M | title = Suppressive effect of intravenous immunoglobulin on peripheral blood neutrophil count in patients with idiopathic thrombocytopenic purpura | journal = Journal of Pediatric Hematology/Oncology | volume = 27 | issue = 1 | pages = 7–10 | date = January 2005 | pmid = 15654271 | doi = 10.1097/01.mph.0000149239.68396.72 }}</ref> Possible pathomechanisms include [[apoptosis]]/cell death due to antineutrophil antibodies with or without neutrophil migration into a storage pool outside the blood circulation.<ref>{{cite journal | vauthors = Stoevesandt J, Heitmann J, Goebeler M, Benoit S | title = [Not Available] | journal = Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology | volume = 18 | issue = 12 | pages = 1394–1404 | date = December 2020 | pmid = 33373142 | doi = 10.1111/ddg.14310_g | doi-access = free }}</ref> |
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In the case of less serious side effects, a patient's infusion rate can be adjusted downwards until the side effects become tolerable, while in the case of more serious side effects, emergency medical attention should be sought.<ref name=scriptinfo>{{cite web | title=Hyqvia (immune globulin 10 percent- human with recombinant human hyaluronidase) kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | access-date=1 May 2020 | archive-date=5 August 2020 | archive-url=https://web.archive.org/web/20200805002533/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ca2c26f-4be2-48cd-be5b-486e350654ba | url-status=live }}</ref> |
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Immunoglobulin therapy |
Immunoglobulin therapy interferes with the ability of the body to produce a normal immune response to an attenuated [[live-virus vaccine]] (like MMR) for up to a year,<ref name=dyna/> can result in falsely elevated blood glucose levels,<ref name=dyna/> and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection.<ref name=citm>{{cite journal| vauthors = Lichtiger B | journal = Current Issues in Transfusion Medicine | date = April 1994 | volume = 3 | pages = 1–7 |title= Laboratory Serologic Problems Associated with Administration of Intravenous IgG |url= http://www3.mdanderson.org/~citm/H-94-04.html|publisher=The University of Texas M. D. Anderson Cancer Center|access-date=23 November 2015|url-status=dead|archive-url=https://web.archive.org/web/20160305122623/http://www3.mdanderson.org/~citm/H-94-04.html|archive-date=5 March 2016}}</ref> |
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==Routes of administration== |
==Routes of administration== |
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===1950s – intramuscular=== |
===1950s – intramuscular=== |
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After immunoglobulin therapy's discovery |
After immunoglobulin therapy's discovery in 1952, weekly [[intramuscular injection]]s of immunoglobulin (IMIg) were the norm until [[Intravenous therapy|intravenous]] formulations (IVIg) began to be introduced in the 1980s.<ref name=scig/> During the mid and late 1950s,{{vague|date=December 2023}} one-time IMIg injections were a common public health response to outbreaks of [[polio]] before the widespread availability of vaccines. Intramuscular injections were extremely poorly tolerated due to their extreme pain and poor efficacy – rarely could intramuscular injections alone raise plasma immunoglobulin levels enough to make a clinically meaningful difference.<ref name=scig/> |
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=== 1980s – intravenous === |
=== 1980s – intravenous === |
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The first description of a [[Subcutaneous injection|subcutaneous]] route of administration for immunoglobulin therapy dates back to 1980,<ref>{{cite journal | vauthors = Misbah S, Sturzenegger MH, Borte M, Shapiro RS, Wasserman RL, Berger M, Ochs HD | title = Subcutaneous immunoglobulin: opportunities and outlook | journal = Clinical and Experimental Immunology | volume = 158 | issue = Suppl 1 | pages = 51–59 | date = December 2009 | pmid = 19883424 | pmc = 2801034 | doi = 10.1111/j.1365-2249.2009.04027.x | doi-access = free | title-link = doi }}</ref> but for many years subcutaneous administration was considered to be a secondary choice, only to be considered when peripheral venous access was no longer possible or tolerable.<ref name=scig/> |
The first description of a [[Subcutaneous injection|subcutaneous]] route of administration for immunoglobulin therapy dates back to 1980,<ref>{{cite journal | vauthors = Misbah S, Sturzenegger MH, Borte M, Shapiro RS, Wasserman RL, Berger M, Ochs HD | title = Subcutaneous immunoglobulin: opportunities and outlook | journal = Clinical and Experimental Immunology | volume = 158 | issue = Suppl 1 | pages = 51–59 | date = December 2009 | pmid = 19883424 | pmc = 2801034 | doi = 10.1111/j.1365-2249.2009.04027.x | doi-access = free | title-link = doi }}</ref> but for many years subcutaneous administration was considered to be a secondary choice, only to be considered when peripheral venous access was no longer possible or tolerable.<ref name=scig/> |
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During the late 1980s and early 1990s, it became obvious that for at least a subset of patients the systemic adverse events associated with intravenous therapy were still not easily tolerable, and more doctors began to experiment with subcutaneous immunoglobulin administration, culminating in an ''ad hoc'' clinical trial in Sweden of 3000 subcutaneous injections administered to 25 adults (most of whom had previously experienced systemic adverse effects with IMIg or IVIg), where no infusion in the ''ad hoc'' trial resulted in a severe systemic adverse reaction, and most subcutaneous injections were able to be administered in non-hospital settings, allowing for considerably more freedom for the people involved.<ref name=scig/> |
During the late 1980s and early 1990s,{{vague|date=December 2023}} it became obvious that for at least a subset of patients the systemic adverse events associated with intravenous therapy were still not easily tolerable, and more doctors began to experiment with subcutaneous immunoglobulin administration, culminating in an ''ad hoc'' clinical trial in Sweden of 3000 subcutaneous injections administered to 25 adults (most of whom had previously experienced systemic adverse effects with IMIg or IVIg), where no infusion in the ''ad hoc'' trial resulted in a severe systemic adverse reaction, and most subcutaneous injections were able to be administered in non-hospital settings, allowing for considerably more freedom for the people involved.<ref name=scig/> |
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In the later 1990s, large-scale trials began in Europe to test the feasibility of subcutaneous immunoglobulin administration, although it was not until 2006 that the first subcutaneous-specific preparation of immunoglobulin was approved by a major regulatory agency ([[Vivaglobin]], which was voluntarily discontinued in 2011).<ref name=scig/><ref name=vivadisc>{{cite web| vauthors = Powell L |title=Re: A Message from CSL Behring to Current Vivaglobin Patients in the United States|url=http://primaryimmune.org/wp-content/uploads/2011/05/Vivaglobin_Letter.pdf|website=Primary Immune Foundation|access-date=24 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151222155226/http://primaryimmune.org/wp-content/uploads/2011/05/Vivaglobin_Letter.pdf|archive-date=22 December 2015}}</ref> A number of other |
In the later 1990s,{{vague|date=December 2023}} large-scale trials began in Europe to test the feasibility of subcutaneous immunoglobulin administration, although it was not until 2006 that the first subcutaneous-specific preparation of immunoglobulin was approved by a major regulatory agency ([[Vivaglobin]], which was voluntarily discontinued in 2011).<ref name=scig/><ref name=vivadisc>{{cite web| vauthors = Powell L |title=Re: A Message from CSL Behring to Current Vivaglobin Patients in the United States|url=http://primaryimmune.org/wp-content/uploads/2011/05/Vivaglobin_Letter.pdf|website=Primary Immune Foundation|access-date=24 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151222155226/http://primaryimmune.org/wp-content/uploads/2011/05/Vivaglobin_Letter.pdf|archive-date=22 December 2015}}</ref> A number of other brand names of subcutaneous immunoglobulin have since been approved, although some small-scale studies have indicated that a particular cohort of patients with [[common variable immunodeficiency]] (CVID) may develop intolerable side effects with subcutaneous immunoglobulin (SCIg) that they do not with intravenous immunoglobulin (IVIg).<ref name=scig/> |
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Although intravenous was the preferred route for immunoglobulin therapy for many years, in 2006, the US [[Food and Drug Administration]] (FDA) approved the first preparation of immunoglobulin that was designed exclusively for subcutaneous use.<ref name=scig>{{cite journal | vauthors = Skoda-Smith S, Torgerson TR, Ochs HD | title = Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease | journal = Therapeutics and Clinical Risk Management | volume = 6 | pages = 1–10 | date = February 2010 | pmid = 20169031 | pmc = 2817783 | doi = 10.2147/tcrm.s4353 | doi-access = free }}</ref> |
Although intravenous was the preferred route for immunoglobulin therapy for many years, in 2006, the US [[Food and Drug Administration]] (FDA) approved the first preparation of immunoglobulin that was designed exclusively for subcutaneous use.<ref name=scig>{{cite journal | vauthors = Skoda-Smith S, Torgerson TR, Ochs HD | title = Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease | journal = Therapeutics and Clinical Risk Management | volume = 6 | pages = 1–10 | date = February 2010 | pmid = 20169031 | pmc = 2817783 | doi = 10.2147/tcrm.s4353 | doi-access = free }}</ref> |
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== Mechanism of action == |
== Mechanism of action == |
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The precise mechanism by which immunoglobulin therapy suppresses harmful [[inflammation]] is likely multifactorial.<ref>{{cite journal |author=Lee Martin N, Butani Lavjay |title=Intravenous Immunoglobulin (IVIG) in Rheumatologic Diseases: A Review of its Mechanism of Action |journal=Current Rheumatology Reviews |volume=1 |issue=3 |pages=289–93 |date= 2005|doi=10.2174/157339705774612355 }}</ref> For example, it has been reported that immunoglobulin therapy can block [[Fas receptor|Fas]]-mediated cell death.<ref>{{cite journal | vauthors = Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, Hunziker T, Saurat JH, Tschopp J, French LE |
The precise mechanism by which immunoglobulin therapy suppresses harmful [[inflammation]] is likely multifactorial.<ref>{{cite journal |author=Lee Martin N, Butani Lavjay |title=Intravenous Immunoglobulin (IVIG) in Rheumatologic Diseases: A Review of its Mechanism of Action |journal=Current Rheumatology Reviews |volume=1 |issue=3 |pages=289–93 |date= 2005|doi=10.2174/157339705774612355 }}</ref> For example, it has been reported that immunoglobulin therapy can block [[Fas receptor|Fas]]-mediated cell death.<ref>{{cite journal | vauthors = Viard I, Wehrli P, Bullani R, Schneider P, Holler N, Salomon D, Hunziker T, Saurat JH, Tschopp J, French LE | title = Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin | journal = Science | volume = 282 | issue = 5388 | pages = 490–493 | date = October 1998 | pmid = 9774279 | doi = 10.1126/science.282.5388.490 | bibcode = 1998Sci...282..490V }}</ref> |
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Perhaps a more popular theory is that the immunosuppressive effects of immunoglobulin therapy are mediated through IgG's [[Fragment crystallizable region|Fc glycosylation]]. By binding to receptors on [[Antigen-presenting cell|antigen presenting cells]], IVIG can increase the expression of the inhibitory [[Fc receptor]], FcgRIIB, and shorten the half-life of auto-reactive antibodies.<ref name = "immune_glycan"/><ref>{{cite journal|author=Gern JE|date=August 2002|title=Antiinflammatory Activity of IVIG Mediated through the Inhibitory FC Receptor|url=https://pediatrics.aappublications.org/content/110/Supplement_2/467.1.full|url-status=live|journal=Pediatrics|volume=110|issue=2|pages=467–68|doi=10.1542/peds.110.S2.467a|archive-url=https://web.archive.org/web/20080611051106/http://pediatrics.aappublications.org/cgi/content/full/110/2/S1/467-b|archive-date=11 June 2008}}</ref><ref>{{cite journal | vauthors = Nimmerjahn F, Ravetch JV | title = The antiinflammatory activity of IgG: the intravenous IgG paradox | journal = The Journal of Experimental Medicine | volume = 204 | issue = 1 | pages = 11–15 | date = January 2007 | pmid = 17227911 | pmc = 2118416 | doi = 10.1084/jem.20061788 }}</ref> The ability of immunoglobulin therapy to suppress pathogenic immune responses by this mechanism is dependent on the presence of a sialylated glycan at position CH2-84.4 of IgG.<ref name = "immune_glycan"/> Specifically, de-sialylated preparations of immunoglobulin lose their therapeutic activity and the anti-inflammatory effects of IVIG can be recapitulated by administration of recombinant sialylated IgG1 Fc.<ref name = "immune_glycan"/> |
Perhaps a more popular theory is that the immunosuppressive effects of immunoglobulin therapy are mediated through IgG's [[Fragment crystallizable region|Fc glycosylation]]. By binding to receptors on [[Antigen-presenting cell|antigen presenting cells]], IVIG can increase the expression of the inhibitory [[Fc receptor]], FcgRIIB, and shorten the half-life of auto-reactive antibodies.<ref name = "immune_glycan"/><ref>{{cite journal|author=Gern JE|date=August 2002|title=Antiinflammatory Activity of IVIG Mediated through the Inhibitory FC Receptor|url=https://pediatrics.aappublications.org/content/110/Supplement_2/467.1.full|url-status=live|journal=Pediatrics|volume=110|issue=2|pages=467–68|doi=10.1542/peds.110.S2.467a|archive-url=https://web.archive.org/web/20080611051106/http://pediatrics.aappublications.org/cgi/content/full/110/2/S1/467-b|archive-date=11 June 2008}}</ref><ref>{{cite journal | vauthors = Nimmerjahn F, Ravetch JV | title = The antiinflammatory activity of IgG: the intravenous IgG paradox | journal = The Journal of Experimental Medicine | volume = 204 | issue = 1 | pages = 11–15 | date = January 2007 | pmid = 17227911 | pmc = 2118416 | doi = 10.1084/jem.20061788 }}</ref> The ability of immunoglobulin therapy to suppress pathogenic immune responses by this mechanism is dependent on the presence of a sialylated glycan at position CH2-84.4 of IgG.<ref name = "immune_glycan"/> Specifically, de-sialylated preparations of immunoglobulin lose their therapeutic activity and the anti-inflammatory effects of IVIG can be recapitulated by administration of recombinant sialylated IgG1 Fc.<ref name = "immune_glycan">{{cite journal | vauthors = Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB | title = Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review | journal = Journal of Autoimmunity | volume = 57 | issue = 6 | pages = 1–13 | date = February 2015 | pmid = 25578468 | pmc = 4340844 | doi = 10.1016/j.jaut.2014.12.002 }}</ref> |
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Sialylated-Fc-dependent mechanism was not reproduced in other experimental models suggesting that this mechanism is functional under a particular disease or experimental settings.<ref>{{cite journal | vauthors = Galeotti C, Kaveri SV, Bayry J | title = IVIG-mediated effector functions in autoimmune and inflammatory diseases | journal = International Immunology | volume = 29 | issue = 11 | pages = 491–498 | date = December 2017 | pmid = 28666326 | doi = 10.1093/intimm/dxx039 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Maddur MS, Kaveri SV, Bayry J | title = Circulating Normal IgG as Stimulator of Regulatory T Cells: Lessons from Intravenous Immunoglobulin | journal = Trends in Immunology | volume = 38 | issue = 11 | pages = 789–792 | date = November 2017 | pmid = 28916232 | doi = 10.1016/j.it.2017.08.008 | url = https://hal.sorbonne-universite.fr/hal-01630293/file/Trends%20Immunol%20Forum%20BAYRY_R1_JD_JB.pdf | access-date = 12 January 2022 | archive-date = 1 February 2022 | archive-url = https://web.archive.org/web/20220201070005/https://hal.sorbonne-universite.fr/hal-01630293/file/Trends%20Immunol%20Forum%20BAYRY_R1_JD_JB.pdf | url-status = live }}</ref><ref>{{cite journal | vauthors = Othy S, Topçu S, Saha C, Kothapalli P, Lacroix-Desmazes S, Käsermann F, Miescher S, Bayry J, Kaveri SV |
Sialylated-Fc-dependent mechanism was not reproduced in other experimental models suggesting that this mechanism is functional under a particular disease or experimental settings.<ref>{{cite journal | vauthors = Galeotti C, Kaveri SV, Bayry J | title = IVIG-mediated effector functions in autoimmune and inflammatory diseases | journal = International Immunology | volume = 29 | issue = 11 | pages = 491–498 | date = December 2017 | pmid = 28666326 | doi = 10.1093/intimm/dxx039 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Maddur MS, Kaveri SV, Bayry J | title = Circulating Normal IgG as Stimulator of Regulatory T Cells: Lessons from Intravenous Immunoglobulin | journal = Trends in Immunology | volume = 38 | issue = 11 | pages = 789–792 | date = November 2017 | pmid = 28916232 | doi = 10.1016/j.it.2017.08.008 | url = https://hal.sorbonne-universite.fr/hal-01630293/file/Trends%20Immunol%20Forum%20BAYRY_R1_JD_JB.pdf | access-date = 12 January 2022 | archive-date = 1 February 2022 | archive-url = https://web.archive.org/web/20220201070005/https://hal.sorbonne-universite.fr/hal-01630293/file/Trends%20Immunol%20Forum%20BAYRY_R1_JD_JB.pdf | url-status = live }}</ref><ref>{{cite journal | vauthors = Othy S, Topçu S, Saha C, Kothapalli P, Lacroix-Desmazes S, Käsermann F, Miescher S, Bayry J, Kaveri SV | title = Sialylation may be dispensable for reciprocal modulation of helper T cells by intravenous immunoglobulin | journal = European Journal of Immunology | volume = 44 | issue = 7 | pages = 2059–2063 | date = July 2014 | pmid = 24700174 | doi = 10.1002/eji.201444440 | s2cid = 29700587 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Campbell IK, Miescher S, Branch DR, Mott PJ, Lazarus AH, Han D, Maraskovsky E, Zuercher AW, Neschadim A, Leontyev D, McKenzie BS, Käsermann F | title = Therapeutic effect of IVIG on inflammatory arthritis in mice is dependent on the Fc portion and independent of sialylation or basophils | journal = Journal of Immunology | volume = 192 | issue = 11 | pages = 5031–5038 | date = June 2014 | pmid = 24760152 | doi = 10.4049/jimmunol.1301611| pmc=4025610 }}</ref> On the other hand, several other mechanisms of action and the actual primary targets of immunoglobulin therapy have been reported. In particular, F(ab')2-dependent action of immunoglobulin to inhibit activation of human dendritic cells,<ref>{{cite journal | vauthors = Bayry J, Lacroix-Desmazes S, Carbonneil C, Misra N, Donkova V, Pashov A, Chevailler A, Mouthon L, Weill B, Bruneval P, Kazatchkine MD, Kaveri SV | title = Inhibition of maturation and function of dendritic cells by intravenous immunoglobulin | journal = Blood | volume = 101 | issue = 2 | pages = 758–765 | date = January 2003 | pmid = 12393386 | doi = 10.1182/blood-2002-05-1447 }}</ref> induction of autophagy,<ref>{{cite journal | vauthors = Das M, Karnam A, Stephen-Victor E, Gilardin L, Bhatt B, Kumar Sharma V, Rambabu N, Patil V, Lecerf M, Käsermann F, Bruneval P, Narayanaswamy Balaji K, Benveniste O, Kaveri SV, Bayry J | title = Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy | journal = Cell Death & Disease | volume = 11 | issue = 1 | pages = 50 | date = January 2020 | pmid = 31974400 | doi = 10.1038/s41419-020-2249-y |pmc=6978335 }}</ref> induction of COX-2-dependent PGE-2 in human dendritic cells leading to expansion of regulatory T cells,<ref>{{cite journal | vauthors = Trinath J, Hegde P, Sharma M, Maddur MS, Rabin M, Vallat JM, Magy L, Balaji KN, Kaveri SV, Bayry J | title = Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells | journal = Blood | volume = 122 | issue = 8 | pages = 1419–1427 | date = August 2013 | pmid = 23847198 | doi = 10.1182/blood-2012-11-468264 | doi-access = free }}</ref> inhibition of pathogenic Th17 responses,<ref>{{cite journal | vauthors = Maddur MS, Vani J, Hegde P, Lacroix-Desmazes S, Kaveri SV, Bayry J | title = Inhibition of differentiation, amplification, and function of human TH17 cells by intravenous immunoglobulin | journal = The Journal of Allergy and Clinical Immunology | volume = 127 | issue = 3 | date = March 2011 | pages = 823–30.e1–7 | pmid = 21281961 | doi = 10.1016/j.jaci.2010.12.1102 | s2cid = 2323773 }}</ref> and induction of human basophil activation and IL-4 induction via anti-IgE autoantibodies.<ref>{{cite journal | vauthors = Galeotti C, Stephen-Victor E, Karnam A, Das M, Gilardin L, Maddur MS, Wymann S, Vonarburg C, Chevailler A, Dimitrov JD, Benveniste O, Bruhns P, Kaveri SV, Bayry J | title = Intravenous immunoglobulin induces IL-4 in human basophils by signaling through surface-bound IgE | journal = The Journal of Allergy and Clinical Immunology | volume = 144 | issue = 2 | pages = 524–535.e8 | date = August 2019 | pmid = 30529242 | doi = 10.1016/j.jaci.2018.10.064 | s2cid = 54476352 | url = https://hal.sorbonne-universite.fr/hal-02284256/file/Galeotti%20et%20al.%20-%202019%20-%20Intravenous%20immunoglobulin%20induces%20IL-4%20in%20human%20b.pdf | access-date = 8 July 2022 | archive-date = 7 March 2020 | archive-url = https://web.archive.org/web/20200307031139/https://hal.sorbonne-universite.fr/hal-02284256/file/Galeotti%20et%20al.%20-%202019%20-%20Intravenous%20immunoglobulin%20induces%20IL-4%20in%20human%20b.pdf | url-status = live }}</ref><ref>{{cite journal | vauthors = Galeotti C, Karnam A, Dimitrov JD, Chevailler A, Kaveri SV, Bayry J | title = Anti-IgE IgG autoantibodies isolated from therapeutic normal IgG intravenous immunoglobulin induce basophil activation | journal = Cellular & Molecular Immunology | volume = 17 | issue = 4 | pages = 426–429 | date = April 2020 | pmid = 31797906 | doi = 10.1038/s41423-019-0334-x|pmc=7109030 }}</ref> Some believe that immunoglobulin therapy may work via a multi-step model where the injected immunoglobulin first forms a type of [[immune complex]] in the patient.<ref>{{cite journal | vauthors = Clynes R | title = Immune complexes as therapy for autoimmunity | journal = The Journal of Clinical Investigation | volume = 115 | issue = 1 | pages = 25–27 | date = January 2005 | pmid = 15630438 | pmc = 539209 | doi = 10.1172/JCI23994 }}</ref> Once these immune complexes are formed, they can interact with Fc receptors on [[dendritic cells]],<ref>{{cite journal | vauthors = Siragam V, Crow AR, Brinc D, Song S, Freedman J, Lazarus AH | title = Intravenous immunoglobulin ameliorates ITP via activating Fc gamma receptors on dendritic cells | journal = Nature Medicine | volume = 12 | issue = 6 | pages = 688–692 | date = June 2006 | pmid = 16715090 | doi = 10.1038/nm1416 | s2cid = 40468774 }}</ref> which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state. |
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Other proposed mechanisms include the possibility that donor antibodies may bind directly with the abnormal host antibodies, stimulating their removal; the possibility that IgG stimulates the host's [[complement system]], leading to enhanced removal of all antibodies, including the harmful ones; and the ability of immunoglobulin to block the antibody receptors on immune cells ([[macrophage]]s), leading to decreased damage by these cells, or regulation of macrophage [[phagocytosis]]. Indeed, it is becoming more clear that immunoglobulin can bind to a number of membrane receptors on [[T cells]], [[B cells]], and [[monocytes]] that are pertinent to autoreactivity and induction of tolerance to self.<ref name = "immune_glycan"/><ref>{{cite journal | vauthors = Bayry J, Thirion M, Misra N, Thorenoor N, Delignat S, Lacroix-Desmazes S, Bellon B, Kaveri S, Kazatchkine MD |
Other proposed mechanisms include the possibility that donor antibodies may bind directly with the abnormal host antibodies, stimulating their removal; the possibility that IgG stimulates the host's [[complement system]], leading to enhanced removal of all antibodies, including the harmful ones; and the ability of immunoglobulin to block the antibody receptors on immune cells ([[macrophage]]s), leading to decreased damage by these cells, or regulation of macrophage [[phagocytosis]]. Indeed, it is becoming more clear that immunoglobulin can bind to a number of membrane receptors on [[T cells]], [[B cells]], and [[monocytes]] that are pertinent to autoreactivity and induction of tolerance to self.<ref name = "immune_glycan"/><ref>{{cite journal | vauthors = Bayry J, Thirion M, Misra N, Thorenoor N, Delignat S, Lacroix-Desmazes S, Bellon B, Kaveri S, Kazatchkine MD | title = Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases | journal = Neurological Sciences | volume = 24 | issue = Suppl 4 | pages = S217–S221 | date = October 2003 | pmid = 14598046 | doi = 10.1007/s10072-003-0081-7 | s2cid = 5945755 }}</ref> |
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A |
A report stated that immunoglobulin application to activated T cells leads to their decreased ability to engage [[microglia]]. As a result of immunoglobulin treatment of T cells, the findings showed reduced levels of [[tumor necrosis factor-alpha]] and [[interleukin-10]] in T cell-microglia co-culture. The results add to the understanding of how immunoglobulin may affect inflammation of the central nervous system in autoimmune inflammatory diseases.<ref>{{cite journal | vauthors = Janke AD, Yong VW | title = Impact of IVIg on the interaction between activated T cells and microglia | journal = Neurological Research | volume = 28 | issue = 3 | pages = 270–274 | date = April 2006 | pmid = 16687052 | doi = 10.1179/016164106X98143 | s2cid = 18239570 }}</ref> |
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==Hyperimmune globulin== |
==Hyperimmune globulin== |
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Hyperimmune globulins are a class of [[immunoglobulin]]s prepared in a similar way as for ''normal human immunoglobulin'', except that the donor has high titers of [[antibody]] against a specific organism or [[antigen]] in their [[Blood plasma|plasma]]. Some agents against which hyperimmune globulins are available include [[hepatitis B]], [[rabies]], [[tetanus]] toxin, [[Varicella zoster virus|varicella-zoster]], etc. Administration of hyperimmune globulin provides [[Passive immunity|"passive" immunity]] to the patient against an agent. This is in contrast to [[vaccine]]s that provide [[Active immunity|"active" immunity]]. However, vaccines take much longer to achieve that purpose while hyperimmune globulin provides instant "passive" short-lived immunity. Hyperimmune globulin may have serious [[side effect]]s, thus usage is taken very seriously.{{citation needed|date=December 2021}} |
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Hyperimmune [[Serum (blood)|serum]] and [[Blood plasma|plasma]] contain high amounts of an antibody, as a consequence of disease convalescence<ref>{{cite journal | vauthors = Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR |
Hyperimmune [[Serum (blood)|serum]] and [[Blood plasma|plasma]] contain high amounts of an antibody, as a consequence of disease convalescence<ref>{{cite journal | vauthors = Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR | title = The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis | journal = The Journal of Infectious Diseases | volume = 211 | issue = 1 | pages = 80–90 | date = January 2015 | pmid = 25030060 | pmc = 4264590 | doi = 10.1093/infdis/jiu396 }}</ref> or of repeated immunization.<ref>{{cite web |title=Antivenoms |url=https://www.who.int/teams/control-of-neglected-tropical-diseases/snakebite-envenoming/antivenoms |access-date=23 May 2023 |website=www.who.int |language=en}}</ref> Hyperimmune plasma is used in veterinary medicine,<ref>{{cite web |date=20 May 2021 |title=What is Hyperimmunized Plasma? |url=https://plasvaccusa.com/what-is-hyperimmunized-plasma/ |access-date=23 May 2023 |website=Plasvacc USA |language=en-US}}</ref> and hyperimmune plasma derivatives are used to treat snakebite.<ref>{{cite journal | vauthors = Dias da Silva W, De Andrade SA, Megale ÂA, De Souza DA, Sant'Anna OA, Magnoli FC, Guidolin FR, Godoi KS, Saladini LY, Spencer PJ, Portaro FC | title = Antibodies as Snakebite Antivenoms: Past and Future | journal = Toxins | volume = 14 | issue = 9 | pages = 606 | date = September 2022 | pmid = 36136544 | pmc = 9503307 | doi = 10.3390/toxins14090606 | doi-access = free }}</ref> It has been hypothesized that hyperimmune serum may be an effective therapy for persons infected with the [[Ebola virus]].<ref>{{cite journal | vauthors = Kudoyarova-Zubavichene NM, Sergeyev NN, Chepurnov AA, Netesov SV | title = Preparation and use of hyperimmune serum for prophylaxis and therapy of Ebola virus infections | journal = The Journal of Infectious Diseases | volume = 179 | issue = Suppl 1 | pages = S218–S223 | date = February 1999 | pmid = 9988187 | doi = 10.1086/514294 | title-link = doi | doi-access = free }}</ref> |
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==Society and culture== |
==Society and culture== |
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=== Economics === |
=== Economics === |
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In the United Kingdom a dose cost the [[NHS]] between [[GBP|{{GBP}}]]11.20 and {{GBP}}1,200.00 depending on the type and amount.<ref name=BNF69/> In the United States, antivenoms may cost thousands of dollars per dose because of markups that occur after manufacturing.<ref>{{ |
In the United Kingdom a dose cost the [[NHS]] between [[GBP|{{GBP}}]]11.20 and {{GBP}}1,200.00 depending on the type and amount.<ref name=BNF69/> In the United States, antivenoms may cost thousands of dollars per dose because of markups that occur after manufacturing.<ref>{{cite news | vauthors = Ingraham C |date=25 November 2021 |title=The crazy reason it costs $14,000 to treat a snakebite with $14 medicine |language=en-US |newspaper=Washington Post |url=https://www.washingtonpost.com/news/wonk/wp/2015/09/09/the-crazy-reason-it-costs-14000-to-treat-a-snakebite-with-14-medicine/ |access-date=23 May 2023 |issn=0190-8286}}</ref> |
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===Brand names=== |
===Brand names=== |
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As [[Biopharmaceutical|biologicals]], various |
As [[Biopharmaceutical|biologicals]], various brand names of immunoglobulin products are not necessarily interchangeable, and care must be exercised when changing between them.<ref name=aaaiguiding>{{cite web|title=Eight Guiding Principles for Effective Use of IVIG for Patients with Primary Immunodeficiency|url=http://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|publisher=American Association of Allergists and Immunologists|access-date=23 November 2015|url-status=live|archive-url=https://web.archive.org/web/20160305025940/https://www.aaaai.org/Aaaai/media/MediaLibrary/PDF%20Documents/Practice%20Resources/IVIG-guiding-principles.pdf|archive-date=5 March 2016}}</ref> Brand names of intravenous immunoglobulin formulations include Flebogamma, Gamunex, Privigen, Octagam, and Gammagard, while brand names of subcutaneous formulations include Cutaquig, Cuvitru, HyQvia, Hizentra,<ref name="Hizentra EPAR" /><ref>{{cite web | title=Hizentra | website=U.S. [[Food and Drug Administration]] (FDA) | date=15 March 2018 | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/hizentra | access-date=3 May 2020 | archive-date=1 April 2020 | archive-url=https://web.archive.org/web/20200401234108/https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/hizentra | url-status=live }}</ref><ref>{{cite report|url=https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM601862.pdf|title=Summary Basis for Regulatory Action – Hizentra| vauthors = Pierce LR |date=14 March 2018|publisher=U.S. [[Food and Drug Administration]] (FDA)|access-date=20 March 2018|others=Review Office Signatory Authority Tejashri Purohit-Sheth|archive-date=20 March 2018|archive-url=https://web.archive.org/web/20180320232958/https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM601862.pdf|url-status=live}}</ref> Gamunex-C, and Gammaked.<ref name=brands>{{cite journal| vauthors = Berman K |title=SCIG: New Therapeutic Uses Beyond PI?|journal=IG Living|issue=February–March 2015|pages=28–32|url=http://www.igliving.com/magazine/articles/IGL_2015-02_AR_SCIG-New-Therapeutic-Uses-Beyond-PI.pdf|access-date=23 November 2015|url-status=live|archive-url=https://web.archive.org/web/20151027084644/http://www.igliving.com/magazine/articles/IGL_2015-02_AR_SCIG-New-Therapeutic-Uses-Beyond-PI.pdf|archive-date=27 October 2015}}</ref> |
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=== Supply issues === |
=== Supply issues === |
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==Research== |
==Research== |
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Experimental results from a small [[clinical trial]] in humans suggested protection against the progression of [[Alzheimer's disease]], but no such benefit was found in a subsequent phase III clinical trial.<ref name="NYT2012">{{cite web|url=https://www.nytimes.com/2012/07/18/business/study-shows-drug-may-help-alzheimers-patients.html|title=Small Trial Hints Drug Can Slow Alzheimer's|author=Andrew Pollack|date=17 July 2012|work=New York Times|url-access=registration|url-status=live|archive-url=https://web.archive.org/web/20120719123729/http://www.nytimes.com/2012/07/18/business/study-shows-drug-may-help-alzheimers-patients.html|archive-date=19 July 2012|access-date=19 July 2012}}</ref><ref>{{cite web|url=http://www.cbsnews.com/8301-504763_162-57474035-10391704/experimental-alzheimers-drug-gammagard-may-stall-memory-decline-small-study-suggests/|title=Experimental Alzheimer's drug Gammagard may stall memory decline, small study suggests|publisher=CBS News|date=17 July 2012|access-date=19 July 2012|url-status=live|archive-url=https://web.archive.org/web/20120719063457/http://www.cbsnews.com/8301-504763_162-57474035-10391704/experimental-alzheimers-drug-gammagard-may-stall-memory-decline-small-study-suggests/|archive-date=19 July 2012}}</ref><ref>{{ |
Experimental results from a small [[clinical trial]] in humans suggested protection against the progression of [[Alzheimer's disease]], but no such benefit was found in a subsequent phase III clinical trial.<ref name="NYT2012">{{cite web|url=https://www.nytimes.com/2012/07/18/business/study-shows-drug-may-help-alzheimers-patients.html|title=Small Trial Hints Drug Can Slow Alzheimer's|author=Andrew Pollack|date=17 July 2012|work=New York Times|url-access=registration|url-status=live|archive-url=https://web.archive.org/web/20120719123729/http://www.nytimes.com/2012/07/18/business/study-shows-drug-may-help-alzheimers-patients.html|archive-date=19 July 2012|access-date=19 July 2012}}</ref><ref>{{cite web|url=http://www.cbsnews.com/8301-504763_162-57474035-10391704/experimental-alzheimers-drug-gammagard-may-stall-memory-decline-small-study-suggests/|title=Experimental Alzheimer's drug Gammagard may stall memory decline, small study suggests|publisher=CBS News|date=17 July 2012|access-date=19 July 2012|url-status=live|archive-url=https://web.archive.org/web/20120719063457/http://www.cbsnews.com/8301-504763_162-57474035-10391704/experimental-alzheimers-drug-gammagard-may-stall-memory-decline-small-study-suggests/|archive-date=19 July 2012}}</ref><ref>{{cite web|url=http://www.genengnews.com/gen-news-highlights/another-alzheimer-s-drug-fails-phase-iii-trial/81248326/|archive-url=https://web.archive.org/web/20130607013806/http://www.genengnews.com/gen-news-highlights/another-alzheimer-s-drug-fails-phase-iii-trial/81248326|url-status=dead|title=Another Alzheimer's Drug Fails Phase III Trial|archive-date=7 June 2013}}</ref> In May 2020, the US approved a phase three clinical trial on the efficacy and safety of high-concentration intravenous immune globulin therapy in severe [[COVID-19]].<ref>{{cite web|title=FDA Approves Octapharma USA Investigational New Drug Application for Severe COVID-19 Patients|url=https://www.businesswire.com/news/home/20200520005133/en/FDA-Approves-Octapharma-USA-Investigational-New-Drug|date=20 May 2020|website=www.businesswire.com|language=en|access-date=28 May 2020|archive-date=21 June 2020|archive-url=https://web.archive.org/web/20200621081731/https://www.businesswire.com/news/home/20200520005133/en/FDA-Approves-Octapharma-USA-Investigational-New-Drug|url-status=live}}</ref> Efficacy of heterologous immunoglobulin derivatives has been demonstrated in clinical trials of antivenoms for scorpion sting<ref>{{cite journal | vauthors = Boyer LV, Theodorou AA, Berg RA, Mallie J, Chávez-Méndez A, García-Ubbelohde W, Hardiman S, Alagón A | title = Antivenom for critically ill children with neurotoxicity from scorpion stings | journal = The New England Journal of Medicine | volume = 360 | issue = 20 | pages = 2090–2098 | date = May 2009 | pmid = 19439743 | doi = 10.1056/NEJMoa0808455 | doi-access = free }}</ref> and for snakebite.<ref>{{cite journal | vauthors = Williams DJ, Habib AG, Warrell DA | title = Clinical studies of the effectiveness and safety of antivenoms | journal = Toxicon | volume = 150 | pages = 1–10 | date = August 2018 | pmid = 29746978 | doi = 10.1016/j.toxicon.2018.05.001 | s2cid = 13665273 }}</ref> |
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== See also == |
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*[[gammaglobulin]] |
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*[[interferon]] |
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== References == |
== References == |
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{{reflist |
{{reflist}} |
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<ref name="immune_glycan">{{cite journal | vauthors = Maverakis E, Kim K, Shimoda M, Gershwin ME, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB | display-authors = 6 | title = Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: a critical review | journal = Journal of Autoimmunity | volume = 57 | issue = 6 | pages = 1–13 | date = February 2015 | pmid = 25578468 | pmc = 4340844 | doi = 10.1016/j.jaut.2014.12.002 }}</ref> |
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== External links == |
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* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/immune%20globulin | publisher = U.S. National Library of Medicine| work = Drug Information Portal | title = Immune globulin }} |
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{{Medicine}} |
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{{Major drug groups}} |
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{{Immune sera and immunoglobulins}} |
{{Immune sera and immunoglobulins}} |
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{{Intravenous therapy}} |
{{Intravenous therapy}} |
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{{Portal bar | Medicine}} |
{{Portal bar | Medicine}} |
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[[Category:Glycoproteins]] |
[[Category:Glycoproteins]] |
Revision as of 02:29, 16 July 2024
![]() | It has been suggested that this article should be split into a new article titled normal human immunoglobulin. (discuss) (December 2020) |
Clinical data | |
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Trade names | Flebogamma, Gammagard, Hizentra, others |
Other names | normal human immunoglobulin (HNIG), human normal immunoglobulin (HNIG) |
AHFS/Drugs.com | Monograph |
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Routes of administration | Intravenous, intramuscular, subcutaneous |
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Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin) to treat several health conditions.[13][14] These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain–Barré syndrome, and certain other infections when a more specific immunoglobulin is not available.[13] Depending on the formulation it can be given by injection into muscle, a vein, or under the skin.[13] The effects last a few weeks.[14]
Common side effects include pain at the site of injection, muscle pain, and allergic reactions.[13] Other severe side effects include kidney problems, anaphylaxis, blood clots, and red blood cell breakdown.[13] Use is not recommended in people with some types of IgA deficiency.[13] Use appears to be relatively safe during pregnancy.[13] Human immunoglobulin is made from human blood plasma.[13] It contains antibodies against many viruses.[14]
Human immunoglobulin therapy first occurred in the 1930s and a formulation for injection into a vein was approved for medical use in the United States in 1981.[15] It is on the World Health Organization's List of Essential Medicines.[16][17] Each formulation of the product is somewhat different.[14] A number of specific immunoglobulin formulations are also available including for hepatitis B, rabies, tetanus, varicella infection, and Rh positive blood exposure.[14]
Medical uses
Immunoglobulin therapy is used in a variety of conditions, many of which involve decreased or abolished antibody production capabilities, which range from a complete absence of multiple types of antibodies, to IgG subclass deficiencies (usually involving IgG2 or IgG3), to other disorders in which antibodies are within a normal quantitative range, but lacking in quality – unable to respond to antigens as they normally should – resulting in an increased rate or increased severity of infections. In these situations, immunoglobulin infusions confer passive resistance to infection on their recipients by increasing the quantity/quality of IgG they possess. Immunoglobulin therapy is also used for a number of other conditions, including in many autoimmune disorders such as dermatomyositis in an attempt to decrease the severity of symptoms. Immunoglobulin therapy is also used in some treatment protocols for secondary immunodeficiencies such as human immunodeficiency virus (HIV), some autoimmune disorders (such as immune thrombocytopenia and Kawasaki disease), some neurological diseases (multifocal motor neuropathy, stiff person syndrome, multiple sclerosis and myasthenia gravis) some acute infections and some complications of organ transplantation.[18]
Immunoglobulin therapy is especially useful in some acute infection cases such as pediatric HIV infection and is also considered the standard of treatment for some autoimmune disorders such as Guillain–Barré syndrome.[19][20] The high demand which coupled with the difficulty of producing immunoglobulin in large quantities has resulted in increasing global shortages, usage limitations and rationing of immunoglobulin.[21]
Australien
The Australian Red Cross Blood Service developed their own guidelines for the appropriate use of immunoglobulin therapy in 1997.[22] Immunoglobulin is funded under the National Blood Supply and indications are classified as either an established or emerging therapeutic role or conditions for which immunoglobulin use is in exceptional circumstances only.[23]
Subcutaneous immunoglobulin access programs have been developed to facilitate hospital based programs.[24]
Human normal immunoglobulin (human immunoglobulin G) (Cutaquig) was approved for medical use in Australia in May 2021.[25]
Kanada
The National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services have also developed their own separate set of guidelines for the appropriate use of immunoglobulin therapy, which strongly support the use of immunoglobulin therapy in primary immunodeficiencies and some complications of HIV, while remaining silent on the issues of sepsis, multiple sclerosis, and chronic fatigue syndrome.[26]
European Union
Brands include HyQvia (human normal immunoglobulin), Privigen (human normal immunoglobulin (IVIg)), Hizentra (human normal immunoglobulin (SCIg)), Kiovig (human normal immunoglobulin), and Flebogamma DIF (human normal immunoglobulin).[12][27][28][29]
In the EU human normal immunoglobulin (SCIg) (Hizentra) is used in people whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins.[27] It is used to treat the following conditions:
- primary immunodeficiency syndromes (PID, when people are born with an inability to produce enough antibodies);[27]
- low levels of antibodies in the blood in people with chronic lymphocytic leukaemia (a cancer of a type of white blood cell) or myeloma (a cancer of another type of white blood cell) and who have frequent infections;[27]
- low levels of antibodies in the blood in people before or after allogeneic haematopoietic stem cell transplantation (a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells from a donor);[27]
- chronic inflammatory demyelinating polyneuropathy (CIDP). In this rare disease, the immune system (the body's defence system) works abnormally and destroys the protective covering over the nerves.[27]
It is indicated for replacement therapy in adults and children in primary immunodeficiency syndromes such as:
- congenital agammaglobulinaemia and hypogammaglobulinaemia (low levels of antibodies);[27]
- common variable immunodeficiency;[27]
- severe combined immunodeficiency;[27]
- immunoglobulin-G-subclass deficiencies with recurrent infections;[27]
- replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.[27]
Flebogamma DIF is indicated for the replacement therapy in adults, children and adolescents (0–18 years) in:
- primary immunodeficiency syndromes with impaired antibody production;[30]
- hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (a cancer of a type of white blood cell), in whom prophylactic antibiotics have failed;[30]
- hypogammaglobulinaemia (low levels of antibodies) and recurrent bacterial infections in plateau-phase-multiple-myeloma (another cancer of a type of white blood cell) patients who failed to respond to pneumococcal immunisation;[30]
- hypogammaglobulinaemia (low levels of antibodies) in patients after allogenic haematopoietic-stem-cell transplantation (HSCT) (when the patient receives stem cells from a matched donor to help restore the bone marrow);[30]
- congenital acquired immune deficiency syndrome (AIDS) with recurrent bacterial infections.[30]
and for the immunomodulation in adults, children and adolescents (0–18 years) in:
- primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count;[30]
- Guillain–Barré syndrome, which causes multiple inflammations of the nerves in the body;[30]
- Kawasaki disease, which causes multiple inflammation of several organs in the body.[30]
Vereinigtes Königreich
The United Kingdom's National Health Service recommends the routine use of immunoglobulin for a variety of conditions including primary immunodeficiencies and a number of other conditions, but recommends against the use of immunoglobulin in sepsis (unless a specific toxin has been identified), multiple sclerosis, neonatal sepsis, and pediatric HIV/AIDS.[31]
Vereinigte Staaten
The American Academy of Allergy, Asthma, and Immunology supports the use of immunoglobulin for primary immunodeficiencies, while noting that such usage actually accounts for a minority of usage and acknowledging that immunoglobulin supplementation can be appropriately used for a number of other conditions,[32] including neonatal sepsis (citing a sixfold decrease in mortality), considered in cases of HIV (including pediatric HIV), considered as a second line treatment in relapsing-remitting multiple sclerosis, but recommending against its use in such conditions as chronic fatigue syndrome, PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) until further evidence to support its use is found (though noting that it may be useful in PANDAS patients with an autoimmune component), cystic fibrosis, and a number of other conditions.[18]
Brands include:
- Alyglo (immune globulin intravenous human-stwk)[11][33]
- Asceniv (immune globulin intravenous, human – slra)[8]
- Bivigam (immune globulin intravenous – human 10% liquid)[9]
- Gamunex-C, (immune globulin injection human)[10]
- Hizentra (immune globulin subcutaneous human)[34]
- Hyqvia (immune globulin 10 percent – human with recombinant human hyaluronidase)[35]
- Octagam (immune globulin intravenous, human)[36]
- Panzyga (immune globulin intravenous, human – ifas)[37]
- Xembify (immune globulin subcutaneous, human – klhw)[38]
Side effects
Although immunoglobulin is frequently used for long periods of time and is generally considered safe, immunoglobulin therapy can have severe adverse effects, both localized and systemic. Subcutaneous administration of immunoglobulin is associated with a lower risk of both systemic and localized risk when compared to intravenous administration (hyaluronidase-assisted subcutaneous administration is associated with a greater frequency of adverse effects than traditional subcutaneous administration but still a lower frequency of adverse effects when compared to intravenous administration). Patients who are receiving immunoglobulin and experience adverse events are sometimes recommended to take acetaminophen and diphenhydramine before their infusions to reduce the rate of adverse effects. Additional premedication may be required in some instances (especially when first getting accustomed to a new dosage), prednisone or another oral steroid.[citation needed]
Local side effects of immunoglobulin infusions most frequently include an injection site reaction (reddening of the skin around the injection site), itching, rash, and hives.[39] Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.[39]
Serious side effects of immunoglobulin infusions in infants, children,[40] and adults include chest discomfort or pain, myocardial infarction, tachycardia, hyponatremia, hemolysis, hemolytic anemia, thrombosis, hepatitis, anaphylaxis, backache, aseptic meningitis, acute kidney injury, hypokalemic nephropathy, pulmonary embolism, and transfusion related acute lung injury.[39] hemoThere is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient.[39] Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.[41]
IVIG has long been known to induce a decrease in peripheral blood neutrophil count, or neutropenia in neonates,[42] and in patients with Idiopathic Thrombocytopenic Purpura, resolving spontaneously and without complications within 48 h.[43] Possible pathomechanisms include apoptosis/cell death due to antineutrophil antibodies with or without neutrophil migration into a storage pool outside the blood circulation.[44]
Immunoglobulin therapy interferes with the ability of the body to produce a normal immune response to an attenuated live-virus vaccine (like MMR) for up to a year,[39] can result in falsely elevated blood glucose levels,[39] and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection.[45]
Routes of administration
1950s – intramuscular
After immunoglobulin therapy's discovery in 1952, weekly intramuscular injections of immunoglobulin (IMIg) were the norm until intravenous formulations (IVIg) began to be introduced in the 1980s.[46] During the mid and late 1950s,[vague] one-time IMIg injections were a common public health response to outbreaks of polio before the widespread availability of vaccines. Intramuscular injections were extremely poorly tolerated due to their extreme pain and poor efficacy – rarely could intramuscular injections alone raise plasma immunoglobulin levels enough to make a clinically meaningful difference.[46]
1980s – intravenous
Intravenous formulations began to be approved in the 1980s, which represented a significant improvement over intramuscular injections, as they allowed for a sufficient amount of immunoglobulin to be injected to reach clinical efficacy, although they still had a fairly high rate of adverse effects (though the addition of stabilizing agents reduced this further).[46]
1990s – subcutaneous
The first description of a subcutaneous route of administration for immunoglobulin therapy dates back to 1980,[47] but for many years subcutaneous administration was considered to be a secondary choice, only to be considered when peripheral venous access was no longer possible or tolerable.[46]
During the late 1980s and early 1990s,[vague] it became obvious that for at least a subset of patients the systemic adverse events associated with intravenous therapy were still not easily tolerable, and more doctors began to experiment with subcutaneous immunoglobulin administration, culminating in an ad hoc clinical trial in Sweden of 3000 subcutaneous injections administered to 25 adults (most of whom had previously experienced systemic adverse effects with IMIg or IVIg), where no infusion in the ad hoc trial resulted in a severe systemic adverse reaction, and most subcutaneous injections were able to be administered in non-hospital settings, allowing for considerably more freedom for the people involved.[46]
In the later 1990s,[vague] large-scale trials began in Europe to test the feasibility of subcutaneous immunoglobulin administration, although it was not until 2006 that the first subcutaneous-specific preparation of immunoglobulin was approved by a major regulatory agency (Vivaglobin, which was voluntarily discontinued in 2011).[46][48] A number of other brand names of subcutaneous immunoglobulin have since been approved, although some small-scale studies have indicated that a particular cohort of patients with common variable immunodeficiency (CVID) may develop intolerable side effects with subcutaneous immunoglobulin (SCIg) that they do not with intravenous immunoglobulin (IVIg).[46]
Although intravenous was the preferred route for immunoglobulin therapy for many years, in 2006, the US Food and Drug Administration (FDA) approved the first preparation of immunoglobulin that was designed exclusively for subcutaneous use.[46]
Mechanism of action
The precise mechanism by which immunoglobulin therapy suppresses harmful inflammation is likely multifactorial.[49] For example, it has been reported that immunoglobulin therapy can block Fas-mediated cell death.[50]
Perhaps a more popular theory is that the immunosuppressive effects of immunoglobulin therapy are mediated through IgG's Fc glycosylation. By binding to receptors on antigen presenting cells, IVIG can increase the expression of the inhibitory Fc receptor, FcgRIIB, and shorten the half-life of auto-reactive antibodies.[51][52][53] The ability of immunoglobulin therapy to suppress pathogenic immune responses by this mechanism is dependent on the presence of a sialylated glycan at position CH2-84.4 of IgG.[51] Specifically, de-sialylated preparations of immunoglobulin lose their therapeutic activity and the anti-inflammatory effects of IVIG can be recapitulated by administration of recombinant sialylated IgG1 Fc.[51]
Sialylated-Fc-dependent mechanism was not reproduced in other experimental models suggesting that this mechanism is functional under a particular disease or experimental settings.[54][55][56][57] On the other hand, several other mechanisms of action and the actual primary targets of immunoglobulin therapy have been reported. In particular, F(ab')2-dependent action of immunoglobulin to inhibit activation of human dendritic cells,[58] induction of autophagy,[59] induction of COX-2-dependent PGE-2 in human dendritic cells leading to expansion of regulatory T cells,[60] inhibition of pathogenic Th17 responses,[61] and induction of human basophil activation and IL-4 induction via anti-IgE autoantibodies.[62][63] Some believe that immunoglobulin therapy may work via a multi-step model where the injected immunoglobulin first forms a type of immune complex in the patient.[64] Once these immune complexes are formed, they can interact with Fc receptors on dendritic cells,[65] which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state.
Other proposed mechanisms include the possibility that donor antibodies may bind directly with the abnormal host antibodies, stimulating their removal; the possibility that IgG stimulates the host's complement system, leading to enhanced removal of all antibodies, including the harmful ones; and the ability of immunoglobulin to block the antibody receptors on immune cells (macrophages), leading to decreased damage by these cells, or regulation of macrophage phagocytosis. Indeed, it is becoming more clear that immunoglobulin can bind to a number of membrane receptors on T cells, B cells, and monocytes that are pertinent to autoreactivity and induction of tolerance to self.[51][66]
A report stated that immunoglobulin application to activated T cells leads to their decreased ability to engage microglia. As a result of immunoglobulin treatment of T cells, the findings showed reduced levels of tumor necrosis factor-alpha and interleukin-10 in T cell-microglia co-culture. The results add to the understanding of how immunoglobulin may affect inflammation of the central nervous system in autoimmune inflammatory diseases.[67]
Hyperimmune globulin
Hyperimmune globulins are a class of immunoglobulins prepared in a similar way as for normal human immunoglobulin, except that the donor has high titers of antibody against a specific organism or antigen in their plasma. Some agents against which hyperimmune globulins are available include hepatitis B, rabies, tetanus toxin, varicella-zoster, etc. Administration of hyperimmune globulin provides "passive" immunity to the patient against an agent. This is in contrast to vaccines that provide "active" immunity. However, vaccines take much longer to achieve that purpose while hyperimmune globulin provides instant "passive" short-lived immunity. Hyperimmune globulin may have serious side effects, thus usage is taken very seriously.[citation needed]
Hyperimmune serum and plasma contain high amounts of an antibody, as a consequence of disease convalescence[68] or of repeated immunization.[69] Hyperimmune plasma is used in veterinary medicine,[70] and hyperimmune plasma derivatives are used to treat snakebite.[71] It has been hypothesized that hyperimmune serum may be an effective therapy for persons infected with the Ebola virus.[72]
Society and culture
Wirtschaft
In the United Kingdom a dose cost the NHS between £11.20 and £1,200.00 depending on the type and amount.[14] In the United States, antivenoms may cost thousands of dollars per dose because of markups that occur after manufacturing.[73]
Brand names
As biologicals, various brand names of immunoglobulin products are not necessarily interchangeable, and care must be exercised when changing between them.[74] Brand names of intravenous immunoglobulin formulations include Flebogamma, Gamunex, Privigen, Octagam, and Gammagard, while brand names of subcutaneous formulations include Cutaquig, Cuvitru, HyQvia, Hizentra,[27][75][76] Gamunex-C, and Gammaked.[77]
Supply issues
The United States is one of a handful of countries that allow plasma donors to be paid, meaning that the US supplies much of the plasma-derived medicinal products (including immunoglobulin) used across the world, including more than 50% of the European Union's supply.[78] The Council of Europe has officially endorsed the idea of not paying for plasma donations for both ethical reasons and reasons of safety, but studies have found that relying on entirely voluntary plasma donation leads to shortages of immunoglobulin and forces member countries to import immunoglobulin from countries that do compensate donors.[78]
In Australia, blood donation is voluntary and therefore to cope with increasing demand and to reduce the shortages of locally produced immunoglobulin, several programs have been undertaken including adopting plasma for first time blood donors, better processes for donation, plasma donor centres and encouraging current blood donors to consider plasma only donation.[79]
Forschung
Experimental results from a small clinical trial in humans suggested protection against the progression of Alzheimer's disease, but no such benefit was found in a subsequent phase III clinical trial.[80][81][82] In May 2020, the US approved a phase three clinical trial on the efficacy and safety of high-concentration intravenous immune globulin therapy in severe COVID-19.[83] Efficacy of heterologous immunoglobulin derivatives has been demonstrated in clinical trials of antivenoms for scorpion sting[84] and for snakebite.[85]
References
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- ^ Hughes RA, Wijdicks EF, Barohn R, Benson E, Cornblath DR, Hahn AF, et al. (September 2003). "Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology". Neurology. 61 (6): 736–740. doi:10.1212/WNL.61.6.736. PMID 14504313. S2CID 20577426.
- ^ Pondrom S (October 2014). "The IVIg dilemma". The AJT Report. American Journal of Transplantation. 14 (10): 2195–2196. doi:10.1111/ajt.12995. PMID 25231064. S2CID 221433035.
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