**2.1 Role of ANCA antibodies and neutrophils**

ANCAs, which represent autoantibodies directed against neutrophil cytoplasmic proteins, recognize a range of antigens. Only two relevant protein targets are identified, called proteinase 3 (PR3) and myeloperoxidase (MPO). These proteins are found in the primary granules of neutrophils and are involved in defense against microbes [5]**.**

During AAV and in small vessels, a pathological and sustained interaction occurs between ANCA and abnormally activated neutrophils. Thus, in the systemic form of GPA, ANCAs recognize PR3 in about 75% of cases. Whereas MPO-ANCA is more commonly associated with MPA (60%) and EGPA (50%) [5–7].

Experimental and clinical data provide evidence that ANCAs and neutrophils are the key players in pathogenesis. In response to inflammation or infection, neutrophils exposed to cytokines (interleukin 1, tumor necrosis factor α…) or complement C5a become primed with movement of MPO and PR3 from primary granules to the cell surface. ANCAs bind to these autoantigens on the neutrophil surface. Neutrophils become activated and bind to vascular endothelium, resulting in tissue damage.

## **2.2 Role of the complement system, cellular and humeral immunity**

The pathogenesis of AAV also involves [5–8]

