Specks U. Epitope-specific anti-neutrophil cytoplasmic antibodies: Do they matter? Can they be detected? APMIS 2009; 177: 63–6. Proteinase 3 (PR3)-anti-neutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase (MPO)-ANCA are suggested to play a pathogenic role as they are closely related to the small-vessel vasculitis syndromes, Wegener's granulomatosis and microscopic polyangiitis. A large body of in vitro and animal experiments supports this concept. The mechanisms of action involve a direct interaction between ANCA and its antigen. The epitope specificity of ANCA may therefore influence the functional effects of ANCA and/or may reflect the mechanisms behind different disease manifestations or disease courses.