Pathophysiology
Clinical meaning
Acute postinfectious glomerulonephritis (APIGN) represents a prototype of immune complex-mediated glomerular disease driven by the host immune response to nephritogenic strains of group A Streptococcus (GAS). The molecular pathogenesis involves formation of circulating IgG and IgA immune complexes against specific nephritogenic antigens, primarily nephritis-associated plasmin receptor (NAPlr) and streptococcal pyrogenic exotoxin B (SPE B). NAPlr binds plasmin and localizes to the glomerulus where it activates the complement cascade through the alternative pathway, generating C3 convertase (C3bBb) that cleaves C3 into C3a (anaphylatoxin) and C3b (opsonin). C3b deposition on the glomerular basement membrane amplifies through the alternative pathway feedback loop, while C5 convertase generates C5a (a potent neutrophil chemoattractant) and initiates formation of the membrane attack complex (C5b-9). The inflammatory cascade proceeds through Fc receptor-mediated mechanisms: deposited IgG immune complexes engage Fc-gamma receptors (FcγRIII and FcγRIV) on infiltrating neutrophils and macrophages, triggering release of reactive oxygen species, matrix metalloproteinases, and pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6). Podocyte injury occurs through both complement-mediated cytotoxicity (sublytic C5b-9 insertion disrupting slit diaphragm integrity) and neutrophil-derived proteases degrading nephrin and podocin proteins. Mesangial cell proliferation is...