Comparative analysis of changes in the complement system in immunoglobulin-mediated and complement-mediated glomerulopathies with the morphological profile of membranoproliferative glomerulonephritis

Aim: to compare changes in the main parameters of the complement system in idiopathic membranoproliferative glomerulonephritis (iMPGN), class IV lupus nephritis (LN IV), C3-glomerulopathy (C3-GP) and atypical hemolytic-uremic syndrome (aHUS). Methods: The study included 8 patients with C3-GP (group 1), 13 patients with iMPGN (group 2), 14 with class IV LN (group 3), and 8 with aHUS in remission (group 4). In all patients, the blood levels of complement system components were examined: C3, C4, C3a, C5a, factor H(CFH) and factor B(CFB), membrane attack complex (MAC), antibodies to C3b(anti-C3b-AT) - a component of alternative complement pathway(AСP) C3 convertase, the level of total hemolytic activity (CH50) and the content of factor D(CFD) in the urine. Results: in all groups, C3 and CH50 levels did not go beyond the reference range, however, in the C3-GP group they were at the lower limit, and the C3 level was significantly lower than in the iMPGN and aHUS groups (p=0.03 and p=0.003). An increased level of CFB was detected in all groups, but in the C3-GP it was significantly lower than in the aHUS (p=0.010). C3a levels were increased in the C3-GP and aHUS groups, and a significant difference was found between the C3-GP and iMPGN groups (p=0.003), C3-GP and class IV LN (p=0.041). MAC levels were increased in all groups, however, maximum values, more than 10 times higher than the reference values, were observed in the C3-GP group and reached statistical significance with groups 2, 3, and 4. In the C3-GP group, a strong inverse relationship was revealed between C3 and MAC (r=-0.826, p=0.011), and in the aHUS group - a direct one (r=0.714, p=0.047). There was a strong negative relationship between CH50 and MAC (r=-0.949, p=0.05) and a very strong correlation between CH50 and C3 (r=1.000, p=0.01) in the C3-GP group. Main conclusions: signs of ACP activation were identified in both types of complement-mediated nephropathy, regardless of the stage of disease. In C3-GP, ACP activation is more pronounced than in aHUS after the acute episode of TMA is relieved. With immune complex MPGN, the changes are less pronounced and indicate an activation of complement along the classical pathway.

альтернативный путь комплемента, МПГН, С3-гломерулопатия, аГУС, alternative complement pathway, MPGN, C3 glomerulopathy, aHUS

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