Autoimmunity in kidney diseases.

Renal involvement in autoimmunity has many facets. Glomerular, tubular and vascular structures are targeted and damaged as a consequence of autoimmune processes. Most dramatic and life-threatening causes are observed with diseases that result in rapidly progressive glomerulonephritis (GN), frequently accompanied by involvement of additional non-renal organs. Typical diseases with these characteristics are anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitidis, anti-glomerular basement membrane (anti-GBM) GN and proliferative lupus nephritis. The leading cause of rapidly progressive GN is ANCA-associated GN and is the main focus of this article. Two major ANCA antigens have been described, namely proteinase 3 (PR3), with a cytoplasmic immunfluorescence staining pattern, and myeloperoxidase (MPO), with a perinuclear pattern. ANCA-associated diseases include Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and a renal limited disease form that presents solely with necrotizing crescentic GN. Because of the strong ANCA association with the aforementioned diseases, ANCA has become a valuable diagnostic tool for clinicians. Moreover, a variety of in vitro and in vivo findings have established the causal role of ANCA in the disease development. Recently, the membrane-PR3 expression pattern on neutrophils was shown to have clinical significance, suggesting membrane-PR3 as a novel biomarker. Furthermore, the data demonstrate that membrane-PR3 expression is restricted to a stable subset of neutrophils. This subset is determined by the existence of the glycosylphosphatidylinositol (GPI)-anchored NB1 receptor (CD177). Better understanding of the PR3-NB1 interaction may have therapeutic implications with the development of more selective drugs.