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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3310-3315.
Prepublished online as a Blood First Edition Paper on July 13, 2007; DOI 10.1182/blood-2007-05-086934.
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Submitted May 18, 2007
Accepted July 11, 2007
HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV-positive Hodgkin lymphoma
Marijke Niens, Ruth F Jarrett, Bouke Hepkema, Ilja M Nolte, Arjan Diepstra, Mathieu Platteel, Niels Kouprie, Craig P Delury, Alice Gallagher, Lydia Visser, Sibrand Poppema, Gerard J te Meerman, and Anke van den Berg*
Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
LRF Virus Centre, Institute of Comparative Medicine, University of Glasgow, Glasgow, United Kingdom
Department of Transplantation Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
* Corresponding author; email: a.van.den.berg{at}path.umcg.nl.
Previous studies showed that the HLA class I region is associated with Epstein-Barr virus (EBV) positive Hodgkin lymphoma (HL) and that HLA-A is the most likely candidate gene in this region. This suggests that antigenic presentation of EBV-derived peptides in the context of HLA-A is involved in the pathogenesis of EBV-positive HL by precluding efficient immune responses. We genotyped exons 2 and 3, encoding the peptide-binding groove of HLA-A, for 32 single nucleotide polymorphisms in 70 EBV-positive and 31 EBV-negative HL patients and 59 controls. HLA-A*01 was significantly overrepresented and HLA-A*02 was significantly underrepresented in EBV-positive HL patients versus controls and EBV-negative HL patients. In addition, HLA-A*02 status was determined by immunohistochemistry or HLA-A*02 specific PCR on 152 EBV-positive and 322 EBV-negative HL cases. The percentage of HLA-A*02 positive patients in the EBV-positive HL group (35.5%) was significantly lower than in 6107 general controls (53.0%) and the EBV-negative HL group (50.9%). Our results indicate that individuals carrying the HLA-A*02 allele have a reduced risk of developing EBV-positive HL, while individuals carrying the HLA-A*01 allele have an increased risk. It is known that HLA-A*02 can present EBV-derived peptides and can evoke an effective immune response, which may explain the protective phenotype.
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