REVIEW Anti-neutrophil cytoplasmic (ANCA) and anti-glomerular basement membrane (GBM) autoantibodies in necrotizing and crescentic glomerulonephritis Sofia Lionaki & J. Charles Jennette & Ronald J. Falk Received: 15 August 2007 / Accepted: 28 September 2007 / Published online: 18 October 2007 # Springer-Verlag 2007 Abstract Anti-neutrophil cytoplasmic autoantibodies (ANCA) and anti-glomerular basement membrane (GBM) necrotizing and crescentic glomerulonephritis are aggressive and destructive glomerular diseases that are associated with and probably caused by circulating ANCA and anti-GBM antibodies. These necrotizing lesions are manifested by acute nephritis and deteriorating kidney function often accompa- nied by distinctive clinical features of systemic disease. Prompt diagnosis requires clinical acumen that allows for the prompt institution of therapy aimed at removing circulating autoantibodies and quelling the inflammatory process. Continuing exploration of the etiology and pathogenesis of these aggressive inflammatory diseases have gradually uncovered new paradigms for the cause of and more specific therapy for these particular glomerular disorders and for autoimmune glomerular diseases in general. Keywords Glomerulonephritis . Crescents . Autoantibodies . ANCA . Anti-GBM Introduction Glomerular crescents, a morphologic expression of severe glomerular injury, were first described in the nineteenth century [1]. Rupture of the glomerular capillaries allows inflammatory mediators to spill into Bowman’ s space resulting in epithelial cell proliferation and monocyte and macrophage invasion [2–4] (Fig. 1a). Immunofluorescence and electron microscopy revealed the heterogeneity of glomerular diseases and led to the classification of crescentic glomerulonephritis into three major categories: pauci-immune glomerulonephritis, most often associated with anti-neutrophil cytoplasmic autoantibody (ANCA) glomerulonephritis, anti-glomerular basement membrane (GBM) glomerulonephritis, and immune complex glomer- ulonephritis (Fig. 1b). This review will focus on the first two categories. Recent advances in understanding the pathogenetic mechanisms, correlations between laboratory and clinical parameters, and related therapies will be discussed. ANCA glomerulonephritis and vasculitis Pauci-immune crescentic glomerulonephritis is most com- monly associated with ANCA, with 80–90% of pauci-immune crescentic glomerulonephritis occurring in ANCA-positive patients [1]. ANCA are antibodies specific for proteins in the cytoplasmic granules of neutrophils and the lysosomes of monocytes. They were first reported by Davies et al. [5] and were correlated with Wegener’ s granulomatosis and micro- scopic polyangiitis [6, 7]. In 1988, it was demonstrated that the vast majority of patients with pauci-immune crescentic glomerulonephritis have ANCA, including patients with or without vasculitis [7]. Two major specificities for ANCA are distinguished on the basis of cytoplasmic (C-ANCA) or perinuclear (P-ANCA) ANCA staining by indirect immunofluorescence microscopy and by enzyme immunoassay demonstrating anti-myeloperoxidase (MPO-ANCA) and anti-proteinase 3 Semin Immunopathol (2007) 29:459–474 DOI 10.1007/s00281-007-0093-0 DO00093; No of Pages S. Lionaki (*) : R. J. Falk UNC Kidney Center, 7011-E Burnett Womack, Chapel Hill, NC 27599-7155, USA e-mail: sofia_lionaki@med.unc.edu J. C. Jennette Department of Pathology and Lab Medicine, Chapel Hill, NC, USA