Pathogenesis of the vascular and glomerular damage in ANCA-positive vasculitis

Pathogenesis of Vascular Inflammation by Anti-Neutrophil Cytoplasmic Antibodies

“…Figure 1 illustrates a hypothetical sequence of pathogenic events that could result in ANCA-mediated vascular inflammation (20).…”

RPGN - Clinical Features, Treatment and Prognosis

“…The hallmark histologic lesions are crescents; a morphologic expression of severe glomerular injury. In severe glomerular injury rupture of the glomerular capillaries allows inflammatory mediators to spill into Bowman's space, resulting in epithelial cell proliferation and invasion of monocyte and macrophage to Bowman's space (Couser, 1988;Jennette & Falk, 1998;Jennette &Thomas, 2001). Crescents are divided into cellular, fibro cellular or fibrous types.…”

ABIN1 in the pathogenesis of Glomerulonephritis and the novel polocyte-neutrophil proinflammatory axis.

“…These circulating antibodies may deposit in the glomerulus through passive means with low or no direct affinity to the glomerular structures, which is the case in Lupus Nephritis (LN) and IgA nephropathy [1,3,4]. In some cases, these antibodies are specific for glomerular structures, as in Goodpasture disease as well as membranous glomerulonephritis (formerly "Idiopathic" GN before identification of the Phospholipase A2 receptor as the autoantigenic target of membranous glomerulonephritis in our lab in 2009) [5][6][7].…”

“…While outcomes and long term histological changes may differ due to systemic or local differences in these conditions, many share the same acute initiating event involving glomerular antibody deposition, and thus novel therapies directed at inhibiting pathogenic changes in this earliest stage of disease may find utility across the GN spectrum [1,3,5,7,12,15]. For a more complete understanding of the events following antibody deposition within the glomerulus, we must first discuss the cellular anatomy of the kidney and the current physiological understanding of the cell types involved in the glomerular response to damage.…”

“…An intrarenal role for neutrophils in the pathogenesis of human GN is implicated by their glomerular accumulation in kidney biopsies from patients with various type of GN (including MPGN, ANCA, LN and α-GBM disease) and inversely by reduction in disease phenotypes with neutrophil depletion in various animal models of GN [3,207,208].…”