Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease Activity

Abstract

The risk allele HLA-DPB1*04:01 has been associated with PR3-ANCA, but its immunopathologic role was unclear. These studies demonstrate that HLA-DPB1*04:01 and PR3_225-239 initiate an immune response. Autoreactive T cells specifically recognized PR3_225-239 presented by HLA-DPB1*04:01. Although larger studies should validate these findings, the pathobiology may explain the observed increased risk of relapse in our cohort. Moreover, lack of HLA and autoantigen interaction observed during long-term remission signals immunologic nonresponsiveness.