Evidence of an Increased Frequency of HLA-DPB1*0301 in Hodgkin’s Disease Supports an Infectious Aetiology

Hodgkin’s disease (HD) may be the rare outcome of a common infection which is influenced by host genetic susceptibility. We have analysed this hypothesis by determining the frequency of HLA-DPB1 alleles in two series of HD patients using molecular typing methods. One series consisted of a retrospective/prospective group of 118 patients over the age of 15 years, and the other a prospective group of 45 patients between the ages of 16 and 24 years. In both series, the proportion of patients typing for HLA-DPB1 *0301 was greater than that for the controls, suggesting that this may be an HD-susceptibility allele. Analysis of DPB1 alleles in relation to HD subtype also showed that the increase in *0301 was present in nodular sclerosing HD (HDNS) patients, as well as in mixed cellularity HD (HDMC) and lymphocyte predominant HD (HDLP) patients. Preliminary evidence was obtained suggesting an increase in *0401, and possibly *0501, in HDMC and HDLP. Analysis of *0301-like hypervariable region (HVR) associations with HD subtypes indicated an increase in an *0301-like HVR-C motif in HDNS, but not in non-HDNS. The frequency of *0301- and *0401 -like HVR-C and HVR-F amino acid residues also differed in HDNS and non-HDNS patients. The frequency of the HVR-C amino acid residues Asp55, Glu56 (*0301) was increased in HDNS, but not in non-HDNS patients, whereas the frequency of Ala55, Ala56 (*0401) was increased in non-HDNS, but not in HDNS patients. In addition, the frequency of the HVR-F amino acid residues Asp84, Glu85 and Ala86 (*0301) was greater in the HDNS than non-HDNS patients, whereas there was no increase in Gly84, Gly85, Pro86 (*0401). Although these are preliminary findings, they suggest that genetic susceptibility to an infectious aetiology in HD may reside at the level of DPB peptide-binding residues rather than with a specific allele.