Anti-neutrophil cytoplasmic antibodies and pathogenesis of small vessel vasculitides

Anti-neutrophil cytoplasmic antibodies (ANCA) are a heterogenous group of autoantibodies with a broad spectrum of clinically associated diseases. ANCA testing has been established as a useful tool for the diagnosis of small vessel vasculitides, especially of ‘ANCA-associated vasculitides’ (AAV), such as Wegenerʹs granulomatosis, microscopic polyangiitis and Churg–Strauss syndrome, in which circulating ANCA are commonly found. Within the last 20 years these antibodies were subject of intensive studies and a growing body of evidence arose for a distinct role of ANCA in the pathogenesis of the AAV. Our current concept of whether ANCA directly or indirectly contribute to vascular damage (ANCA-cytokine-sequence-theory) was mainly developed from in vitro studies and is supported by data from clinical investigations as well as animal models. Recently a direct causal link between ANCA and the development of glomerulonephritis and vasculitis has been demonstrated. We now know that a passive transfer of ANCA is sufficient to induce disease, but it remains to be discovered how the autoantibodies to neutrophil antigens might triggered.