The role of the final litic complement pathway in glomerulonephritis

Sotiraki .M
Chief physician of Nephrology at Renal Unit of General hospital of Amfissa-Central Greece


 The final pathway is activated via the C3-common factor of the classical pathway, the alternative and the lectin through the final formation of the cell membrane attack complex (MAC) who causes lisis of cell. In acute post-streptococcal glomerulonephritis due to β hemolytic Streptococcus group A, the  streptococcal antigens, streptococcal pyrogenic exotoxin, and  NAPlr receptor, circulating or trapped in situ in the basement membrane triggers the formation of antibodies as a result of immune complexes deposited on the glomerulus. There is a decrease of  C1q C2,C4 in the initial phase then is activated the alternative pathway with reduction of C3 and typical placement of IgG-C3-C5 who activate the MAC. The clinical manifestations varies, asymptomatic disease, microscopic hematuria or classic nephritic syndrome. In membranous glomerulonephritis by 75% idiopatic, antibody to phospholipase A2 receptor PLAR cause deposition of subepitelial  immune complex of IgG and complement with activation of MAC and damage of podocyte with non selective proteinuria. There is thickening of basement –membrane with characteristic deposition of igG4 and C3. In anti-GBM glomerulonephritis we have IgG1-IgG3 autoantibodies against the NC1 antigen in the α3 region of type IV collagen and activation of MAC with collagen degradation and cleavage of basement membrane.  Clinically expressed with acute or rapidly progressive renal failure,  moderate grade albuminuria and nephritic sediment. In the membranoproliferative  type III glomerulonephritis , deregulation and prolonged activation of the alternative pathway also activates the final pathway with basement membrane lysis and its transformation.    Typical C3 deposition along the glomerular capillary and mesangial walls without deposition of immunoglobulins. The clinical  manifestations is characterized by microscopic or macroscopic hematuria, significant grade albuminuria and hypertension.