Roles of DRB1*1501 and DRB1*1502 in the pathogenesis of aplastic anemia

Objective Although a number of reports have documented a significantly increased incidence of HLA-DR15 in aplastic anemia (AA), the exact role of HLA-DR15 in the immune mechanisms of AA remains unclear. We herein clarify the difference between DRB1*1501 and DRB1*1502, the two DRB1 alleles that determine the presentation of HLA-DR15, in the pathophysiology of AA. Materials and Methods We investigated the relationships of the patients* HLA-DRB1 allele with both the presence of a small population of CD55−CD59− (PNH-type) blood cells and the response to antithymocyte globulin (ATG) plus cyclosporin (CsA) therapy in 140 Japanese AA patients. Results Of the 30 different DRB1 alleles, only DRB1*1501 (33.6% vs 12.8%, pc < 0.01) and DRB1*1502 (43.6% vs 24.4%, pc < 0.01) displayed significantly higher frequencies among the AA patients than among a control. AA patients possessing HLA-DR15 tended to be old, and especially, the frequency of DRB1*1502 in patients 40 years of age and older (52.4%) was markedly higher than that in those younger than 40 years old (16.2%, pc < 0.01). Only DRB1*1501 was significantly associated with the presence of a small population of PNH-type cells and it also showed a good response to ATG plus CsA therapy in a univariate analysis. A multivariate analysis showed only the presence of a small population of PNH-type cells to be a significant factor associated with a good response to the immunosuppressive therapy (p < 0.01). Conclusions Although both DRB1*1501 and DRB1*1502 contribute to the development of AA, the methods of contribution differ between the two alleles.