HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBVI Hodgkin lymphoma

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+ 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 patients with EBV+ HL, 31 patients with EBV- HL, and 59 control participants. HLA-A*O1 was significantly overrepresented and HLA-A*O2 was significantly underrepresented in patients with EBV+ HL versus controls and patients with EBV- HL. In addition, HLA-A*O2 status was determined by immunohistochemistry or HLA-A*O2-specific polymerase chain reaction (PCR) on 152 patients with EBV+ HL and 322 patients with EBV-HL. The percentage of HLA-A*O2(+) patients in the EBV+ HL group (35.5%) was significantly lower than in 6107 general control participants (53.0%) and the EBV- HL group (50.9%). Our results indicate that individuals carrying the HLA-A*O2 allele have a reduced risk of developing EBV+3 HL, while individuals carrying the HLA-A*O1 allele have an increased risk. It is known that HLA-A*O2 can present EBV-derived peptides and can evoke an effective immune response, which may explain the protective phenotype.