Proteinase 3 Autoreactivity in Anti‐Neutrophil Cytoplasmic Antibody–associated vasculitis—Immunological versus clinical features

ANCA‐associated vasculitis (AAV) is a group of chronic inflammatory diseases of small‐ and medium‐sized vessels, which are broadly subdivided based on organ manifestations and disease‐specific autoantibodies. The so called anti‐neutrophil cytoplasmic antibodies (ANCA) mostly target one of the enzymes, proteinase 3 (PR3) or myeloperoxidase (MPO). Accumulating genetic data demonstrates that these two autoantibodies discriminate two distinct disease entities, more so than the clinical subdivision which is mainly criteria‐based. Treatment of AAV includes heavy immunosuppression and is guided by organs that are involved. Generally, patients with PR3‐ANCA display higher risk for disease relapse than patients with MPO‐ANCA. In this review, we will focus on the autoimmune features of PR3+ AAV and our current understanding of its triggers and the potential translation into clinical practice.