HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma

Hjalgrim, H. et al. (2010) HLA-A alleles and infectious mononucleosis suggest a critical role for cytotoxic T-cell response in EBV-related Hodgkin lymphoma. Proceedings of the National Academy of Sciences of the United States of America, 107(14), pp. 6400-6405. (doi:10.1073/pnas.0915054107)

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Abstract

A proportion of classical Hodgkin lymphoma (HL) is believed to be causally related to infection with the ubiquitous lymphotropic EBV. The determining factors for development of EBV-related HL remain poorly understood, but likely involve immunological control of the viral infection. Accordingly, markers of the HLA class I region have been associated with risk of EBV-related HL. To study the host genetic component of EBV-related HL further, we investigated the lymphoma's association with HLA-A*01 and HLA-A*02 simultaneously in the setting of infectious mononucleosis (IM), a risk factor for EBV-related HL, in a case-series analysis including 278 EBV-related and 656 EBV-unrelated cases of HL. By logistic regression, HLA-A*01 alleles [odds ratio (OR) per allele, 2.15; 95% CI, 1.60-2.88] were associated with increased and HLA-A*02 alleles (OR per allele, 0.70; 95% CI, 0.51-0.97) with decreased risk of EBV-related HL. These allele-specific associations corresponded to nearly 10-fold variation in risk of EBV-related HL between HLA-A*01 and HLA-A*02 homozygotes. History of IM was also associated with risk of EBV-related HL (OR, 3.40; 95% CI, 1.74-6.66). The association between history of IM and EBV- related HL was not seen in the presence of HLA-A*02 because this allele appeared to neutralize the effect of IM on EBV- related HL risk. Our findings suggest that HLA class I-restricted EBV-specific cytotoxic T-cell responses and events in the early immune response to EBV infection in IM play critical roles in the pathogenesis of EBV-related HL.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McConnachie, Dr Alex and Johnson, Dr Paul and Jarrett, Professor Ruth and Lake, Ms Annette and Shield, Ms Lesley
Authors: Hjalgrim, H., Rostgaard, K., Johnson, P.C.D., Lake, A., Shield, L., Little, A.M., Ekstrom-Smedby, K., Adami, H.O., Glimelius, B., Hamilton-Dutoit, S., Kane, E., Taylor, G.M., McConnachie, A., Ryder, L.P., Sundstrom, C., Andersen, P.S., Chang, E.T., Alexander, F.E., Melbye, M., and Jarrett, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:22 March 2010

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