Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes

It has been suggested in a number of studies that susceptibility to adult H odgkin's disease (HD) is influenced by the HLA class II region, and specifi cally by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility t o different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously repor ted associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gende r showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females wi th NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associ ated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance wit h *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorp hic amino-acid frequencies in patients and controls showed that susceptibil ity to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly as sociated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 a lleles and individual DP beta 1 polymorphic amino acid residues may thus af fect susceptibility and resistance to specific HD subtypes. This may be thr ough their influence on the binding of peptides derived from an HD-associat ed infectious agent, and the consequent effect on immune responses to the a gent.