HLA class I associations with EBV+ post-transplant lymphoproliferative disorder.
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.
Blood Cancer Research Laboratory, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia; Clinical Immunohaematology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Kimberley
K
Jones
Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Leesa
L
Wockner
Tissue Type Laboratory, Immunology Department, Pathology Queensland, Brisbane, Australia.
Alycia
A
Thornton
Blood and Marrow Transplant Service, Westmead Hospital, Sydney, Australia.
David
D
Gottlieb
Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
David S
DS
Ritchie
Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
John F
JF
Seymour
Department of Cardiology, St Vincent's Hospital, Sydney, Australia.
Gayathri
G
Kumarasinghe
Blood Cancer Research Laboratory, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia; Department of Haematology, Princess Alexandra Hospital, Brisbane, Australia. Electronic address: M.Gandhi@uq.edu.au.
Maher K
MK
Gandhi
D064591:Allografts; D001315:Australia; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D005260:Female; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006689:Hodgkin Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D017735:Virus Latency / Q000235:genetics / Q000276:immunology
C524866:HLA-A*02 antigen; D015789:HLA-A2 Antigen
Epstein–Barr virus; Genetic association; HLA class I; Post-transplant lymphoproliferative disorder