Disseminated and Congenital Toxoplasmosis in a Mother and Child With Activated PI3-Kinase δ Syndrome Type 2 (APDS2): Case Report and a Literature Review of Toxoplasma Infections in Primary Immunodeficiencies

Djuro Karanovic; Ian C Michelow; Anthony R Hayward; Suk See DeRavin; Ottavia M Delmonte; Michael E Grigg; Adam Kerry Dobbs; Julie E Niemela; Jennifer Stoddard; Zaid Alhinai; Natasha Rybak; Nancy Hernandez; Stefania Pittaluga; Sergio D Rosenzweig; Gulbu Uzel; Luigi D Notarangelo

doi:10.3389/fimmu.2019.00077

Disseminated and Congenital Toxoplasmosis in a Mother and Child With Activated PI3-Kinase δ Syndrome Type 2 (APDS2): Case Report and a Literature Review of Toxoplasma Infections in Primary Immunodeficiencies

Front Immunol. 2019 Feb 14:10:77. doi: 10.3389/fimmu.2019.00077. eCollection 2019.

Authors

Djuro Karanovic¹, Ian C Michelow², Anthony R Hayward³, Suk See DeRavin¹, Ottavia M Delmonte¹, Michael E Grigg⁴, Adam Kerry Dobbs¹, Julie E Niemela⁵, Jennifer Stoddard⁵, Zaid Alhinai², Natasha Rybak⁶, Nancy Hernandez⁷, Stefania Pittaluga⁸, Sergio D Rosenzweig⁵, Gulbu Uzel¹, Luigi D Notarangelo¹

Affiliations

¹ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.
² Division of Infectious Diseases, Department of Pediatrics, Brown University and Rhode Island Hospital, Providence, RI, United States.
³ Division of Allergy and Immunology, Department of Pediatrics, Brown University and Rhode Island Hospital, Providence, RI, United States.
⁴ Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, United States.
⁵ Immunology Service, Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, United States.
⁶ Division of Infectious Diseases, Department of Medicine, Brown University and The Miriam Hospital, Providence, RI, United States.
⁷ Department of Medicine and Pediatrics, Brown University and Rhode Island Hospital, Providence, RI, United States.
⁸ Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, United States.

Abstract

Phosphoinositide 3-kinase (PI3K) plays an integral role in lymphocyte function. Mutations in PIK3CD and PIK3R1, encoding the PI3K p110δ and p85α subunits, respectively, cause increased PI3K activity and result in immunodeficiency with immune dysregulation. We describe here the first cases of disseminated and congenital toxoplasmosis in a mother and child who share a pathogenic mutation in PIK3R1 and review the mechanisms underlying susceptibility to severe Toxoplasma gondii infection in activated PI3Kδ syndrome (APDS) and in other forms of primary immunodeficiency.

Keywords: APDS2; PI3K; PI3K3R1; immunodeficiency; toxoplasmosis.

Publication types

Case Reports
Research Support, N.I.H., Intramural
Review

MeSH terms

Adult
Antibodies, Protozoan / blood
Child
Class I Phosphatidylinositol 3-Kinases / genetics*
Class Ia Phosphatidylinositol 3-Kinase / genetics*
Female
Humans
Immunity, Maternally-Acquired
Immunologic Deficiency Syndromes / diagnosis
Immunologic Deficiency Syndromes / genetics
Immunologic Deficiency Syndromes / immunology*
Infant
Lymphadenopathy
Mothers
Mutation / genetics*
Phenotype
Toxoplasma / physiology*
Toxoplasmosis, Congenital / diagnosis
Toxoplasmosis, Congenital / genetics
Toxoplasmosis, Congenital / immunology*

Substances

Antibodies, Protozoan
PIK3R1 protein, human
Class I Phosphatidylinositol 3-Kinases
Class Ia Phosphatidylinositol 3-Kinase
PIK3CD protein, human