The Role of Complement Component C3 Activation in the Clinical Presentation and Prognosis of IgA Nephropathy—A National Study in Children

Abstract

The aim of the study was to evaluate the influence of the intensity of mesangial C3 deposits in kidney biopsy and the serum C3 level on the clinical course and outcomes of IgAN in children. The study included 148 children from the Polish Pediatric IgAN Registry, diagnosed based on kidney biopsy. Proteinuria, creatinine, IgA, C3 were evaluated twice in the study group, at baseline and the end of follow-up. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The intensity of IgA and C3 deposits were rated from 0 to +4 in immunofluorescence microscopy. The intensity of mesangial C3 > +1 deposits in kidney biopsy has an effect on renal survival with normal GFR in children with IgAN. A reduced serum C3 level has not been a prognostic factor in children but perhaps this finding should be confirmed in a larger group of children.

The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis—A Pilot Study

“…The concentration of urinary vanin-1 correlates negatively with simultaneously measured serum C3 levels. However, in our study, we did not find the prognostic significance of the reduction of C3 in the serum of children with IgAN, which furthermore cannot confirm the prognostic significance of vanin [ 47 ].…”

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

“…, 37 2020 C3 Korea Adult 453 IF 40.3 45 89.5 ± 28.5 0.7 (0.3–1.5) Mizerska-Wasiak et al. , 17 2021 C3 Poland Pediatric 148 IF; plasma, turbidmetric 11.6 67 95.8 ± 33.5 1.4 (0.02–9.6) Lang et al. , 18 2021 C3; IgA/C3 ratio China Pediatric 41 IF:C3;IgA/C3: turbidmetric 9.3 63 118.8 ± 41.2 NA Wu et al.…”

“…, 37 2020 No relationship with MEST-C classes a Mizerska-Wasiak et al. , 17 2021 No relationship with MEST-C classes a Lang et al. , 18 2021 Intense staining (≥2+) associated with M1 class a Wu et al.…”

“…Some studies have suggested that complement activation is associated with more severe MEST-C scores, 11 , 12 , 13 , 14 , 15 whereas others have reported no significant correlation between the 2. 16 , 17 , 18 , 19 …”

Special Issue: New Insights into the Pathogenesis and Therapies of IgA Nephropathy

“…Two reviews focus on the two key factors in IgAN, the autoantigen (galactose-deficient IgA1) and the corresponding autoantibodies (Ohyama et al and Knoppova et al [ 28 , 29 ]), whereas an experimental study postulates that urinary galactose-deficient IgA1 may be a disease-specific biomarker useful for the assessment of disease activity in IgAN (Fukao et al [ 30 ]). Two additional studies consider the role of complement in disease pathogenesis as it relates to therapeutic approaches or the diagnosis and prognosis of disease progression (Poppelaars et al and Mizerska-Wasiak et al [ 31 , 32 ]). Another study postulates that obesity may play a role in mesangial lesions in IgAN (Hong et al [ 33 ]).…”