Human leukocyte antigens and genetic susceptibility to lymphoma

McAulay, K.A. and Jarrett, R.F. (2015) Human leukocyte antigens and genetic susceptibility to lymphoma. Tissue Antigens, 86(2), pp. 98-113. (doi:10.1111/tan.12604) (PMID:26189878)

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Abstract

Familial aggregation, coupled with ethnic variation in incidence, suggests that inherited susceptibility plays a role in the development of lymphoma, and the search for genetic risk factors has highlighted the contribution of the human leukocyte antigen (HLA) complex. In a landmark study published almost 50 years ago, Hodgkin lymphoma (HL) was the first disease to be associated with HLA variation. It is now clear that Epstein-Barr virus (EBV)-positive and -negative HL are strongly associated with specific HLA polymorphisms but these differ by EBV status of the tumours. HLA class I alleles are consistently associated with EBV-positive HL while a polymorphism in HLA class II is the strongest predictor of risk of EBV-negative HL. Recent investigations, particularly genome-wide association studies (GWAS), have also revealed associations between HLA and common types of non-Hodgkin lymphoma (NHL). Follicular lymphoma is strongly associated with two distinct haplotypes in HLA class II whereas diffuse large B-cell lymphoma is most strongly associated with HLA-B*08. Although chronic lymphocytic leukaemia is associated with variation in HLA class II, the strongest signals in GWAS are from non-HLA polymorphisms, suggesting that inherited susceptibility is explained by co-inheritance of multiple low risk variants. Associations between B-cell derived lymphoma and HLA variation suggest that antigen presentation, or lack of, plays an important role in disease pathogenesis but the precise mechanisms have yet to be elucidated.

Item Type:Articles (Other)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jarrett, Professor Ruth and McAulay, Dr Karen
Authors: McAulay, K.A., and Jarrett, R.F.
Subjects:R Medicine > RB Pathology
R Medicine > RZ Other systems of medicine
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Tissue Antigens
Publisher:Wiley
ISSN:0001-2815
ISSN (Online):1399-0039
Published Online:20 July 2015
Copyright Holders:Copyright © 2015 John Wiley and Sons A/S
First Published:First published in Tissue Antigens 86(2): 98-113
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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