POS-029 RARE VARIANTS IN COMPLEMENT GENES AND OUTCOMES OF C3 GLOMERULOPATHY AND IMMUNOGLOBULIN-MEDIATED MPGN

Abstract

IntroductionC3 glomerulopathy (C3G) and idiopathic immunoglobulin-mediated membranoproliferative glomerulonephritis (Ig-MPGN) are rare kidney diseases mediated by dysregulation of the complement alternative pathway. In most cases, complement overactivation is acquired due to the presence of autoantibody targeting C3 convertase. C3G/Ig-MPGN with inherited background are even rarer. However, specific presentation at diagnosis and clinical courses on native kidney and after kidney transplantation are not well known.MethodsRare variant in CFH, CFI and C3 genes (defined by minor allelic frequency bellow 0.1%) were screened in a large national series of 398 patients with C3G (n=296) or Ig-MPGN (n=102) We described genetic, immunological, clinical data at diagnosis and renal outcomes of patients.ResultsView Large Image Figure ViewerDownload Hi-res image Download (PPT)ConclusionsHere, we reported exhaustive clinical, histological and immunological features of the largest series of patients with C3G and Ig-MPGN associated with CFH, CFI or C3 rare variants. Despite an important heterogeneity of clinical features, our result highlights the severity of inherited C3G/Ig-MPGN associated with CFI, CFH or C3 variant, and in particular associated with CFI and C3 variant with early and high degree of recurrence after transplantation.No conflict of interest IntroductionC3 glomerulopathy (C3G) and idiopathic immunoglobulin-mediated membranoproliferative glomerulonephritis (Ig-MPGN) are rare kidney diseases mediated by dysregulation of the complement alternative pathway. In most cases, complement overactivation is acquired due to the presence of autoantibody targeting C3 convertase. C3G/Ig-MPGN with inherited background are even rarer. However, specific presentation at diagnosis and clinical courses on native kidney and after kidney transplantation are not well known. C3 glomerulopathy (C3G) and idiopathic immunoglobulin-mediated membranoproliferative glomerulonephritis (Ig-MPGN) are rare kidney diseases mediated by dysregulation of the complement alternative pathway. In most cases, complement overactivation is acquired due to the presence of autoantibody targeting C3 convertase. C3G/Ig-MPGN with inherited background are even rarer. However, specific presentation at diagnosis and clinical courses on native kidney and after kidney transplantation are not well known. MethodsRare variant in CFH, CFI and C3 genes (defined by minor allelic frequency bellow 0.1%) were screened in a large national series of 398 patients with C3G (n=296) or Ig-MPGN (n=102) We described genetic, immunological, clinical data at diagnosis and renal outcomes of patients. Rare variant in CFH, CFI and C3 genes (defined by minor allelic frequency bellow 0.1%) were screened in a large national series of 398 patients with C3G (n=296) or Ig-MPGN (n=102) We described genetic, immunological, clinical data at diagnosis and renal outcomes of patients. Results ConclusionsHere, we reported exhaustive clinical, histological and immunological features of the largest series of patients with C3G and Ig-MPGN associated with CFH, CFI or C3 rare variants. Despite an important heterogeneity of clinical features, our result highlights the severity of inherited C3G/Ig-MPGN associated with CFI, CFH or C3 variant, and in particular associated with CFI and C3 variant with early and high degree of recurrence after transplantation.No conflict of interest Here, we reported exhaustive clinical, histological and immunological features of the largest series of patients with C3G and Ig-MPGN associated with CFH, CFI or C3 rare variants. Despite an important heterogeneity of clinical features, our result highlights the severity of inherited C3G/Ig-MPGN associated with CFI, CFH or C3 variant, and in particular associated with CFI and C3 variant with early and high degree of recurrence after transplantation.