Proteinase-3 as an autoantigen and the development of granulomatosis with polyangiitis

Human proteinase 3 (hPR3) is a lysosomal enzyme of the serine protease type. In autoimmune vasculitis, autoantibodies to hPR3 appear to have a role in the inception of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), where this protein is the main autoantigen. Indeed, patients with antibodies against hPR3 have more severe symptoms, relapses, and resistance to immunosuppressive therapies, supporting an important role for this autoantigen in the pathophysiology and severity of AAV. In this review, we describe what is known about the role of hPR3 in pathophysiology, diagnosis of AAV, and some perspectives on its treatment.