HLA class I associations with EBV+ post-transplant lymphoproliferative disorder

Kimberley Jones; Leesa Wockner; Alycia Thornton; David Gottlieb; David S Ritchie; John F Seymour; Gayathri Kumarasinghe; Maher K Gandhi

doi:10.1016/j.trim.2015.02.005

HLA class I associations with EBV+ post-transplant lymphoproliferative disorder

Transpl Immunol. 2015 Mar;32(2):126-30. doi: 10.1016/j.trim.2015.02.005. Epub 2015 Feb 27.

Authors

Kimberley Jones¹, Leesa Wockner², Alycia Thornton³, David Gottlieb⁴, David S Ritchie⁵, John F Seymour⁵, Gayathri Kumarasinghe⁶, Maher K Gandhi⁷

Affiliations

¹ Blood Cancer Research Laboratory, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia; Clinical Immunohaematology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
² Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
³ Tissue Type Laboratory, Immunology Department, Pathology Queensland, Brisbane, Australia.
⁴ Blood and Marrow Transplant Service, Westmead Hospital, Sydney, Australia.
⁵ Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
⁶ Department of Cardiology, St Vincent's Hospital, Sydney, Australia.
⁷ Blood Cancer Research Laboratory, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia; Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia. Electronic address: [email protected].

PMID: 25731678
DOI: 10.1016/j.trim.2015.02.005

Abstract

Epstein-Barr virus (EBV) is frequently associated with post-transplant lymphoproliferative disorders (EBV(+) PTLD). In these cases, impaired Epstein-Barr virus (EBV)-specific CD8(+) T-cell immunity is strongly implicated and antigen presentation within the malignant B-cell is intact. Interestingly, several studies have reported HLA class I alleles with protective or susceptibility associations. However, results are conflicting, likely influenced by methodology including inconsistent use of multiple hypothesis testing. By contrast, HLA class I associations have been repeatedly reported for classical Hodgkin Lymphoma (cHL), in which EBV is also implicated in a proportion of cases. In contrast to EBV(+) PTLD which expresses the immunodominant EBV latency III EBNA3A/B/C proteins, EBV(+) cHL is restricted to the subdominant EBNA1/LMP1/LMP2 proteins. Herein, we report a study of HLA class I associations in EBV(+) PTLD, with 263 patients with lymphoma (cHL or PTLD) evaluated. Two Australian population cohorts, n = 23,736 and n = 891 were used for comparison. Contrary to previous reports, no HLA class I associations with EBV(+) PTLD were found, whereas for cHL known HLA class I associations were confirmed, with HLA-A*02 homozygous individuals having the lowest odds of developing EBV(+) cHL. Our results suggest that HLA class I does not influence susceptibility to the viral latency III expressing lymphoma, EBV(+) PTLD. Further studies are required for definitive confirmation.

Keywords: Epstein–Barr virus; Genetic association; HLA class I; Post-transplant lymphoproliferative disorder.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Allografts
Australia
CD8-Positive T-Lymphocytes* / immunology
CD8-Positive T-Lymphocytes* / virology
Female
HLA-A2 Antigen* / genetics
HLA-A2 Antigen* / immunology
Hematopoietic Stem Cell Transplantation*
Herpesvirus 4, Human / physiology*
Hodgkin Disease* / etiology
Hodgkin Disease* / genetics
Hodgkin Disease* / immunology
Hodgkin Disease* / pathology
Humans
Male
Virus Latency* / genetics
Virus Latency* / immunology

Substances

HLA-A*02 antigen
HLA-A2 Antigen