Current findings in the pathogenesis of IgA nephropathy

Academic Article

Abstract

  • © 2017, TIGIS Spol. s.r.o. All rights reserved. IgA nephropathy (IgAN) is an autoimmune disease characterized by mesangial deposition of immune complexes containing polymeric IgA1 (pIgA1) with abnormally low galactose content in oligosaccharides linked by O-glycosidic bond to the hinge region of pIgA1 molecule (Gd-pIgA1). Immune complexes are formed probably in the circulation after recognition of Gd-pIgA1 by affinity-maturated autoantibody of IgG or IgA isotype specifically recognizing a glycan moiety of Gd-pIgA1. Key component of the recognized epitope is N-acetylgalactosamine (GalNAc), linked to amino acids threonine 228 and/or serine 230 of the IgA1 hinge region which is not modified in IgAN patients by attachment of galactose (Gal), in contrast to normal subjects in which typical structure is S/T-GalNAc-Gal. Serum levels of Gd-IgA1 represent promising biomarker. The fraction of above mentioned circulating immune complexes corresponding to the molecular weight 800 - 900 kDa stimulate mesangial cells which is detectable using light microscopy as a the mesangial hypercellularity, segmental glomerulosclerosis and endocapillary hypercellularity, and tubular atrophy or interstitial fibrosis. Affinity maturation of above-described autoantibody leads to the question about their origin, which has been associated with various antigens containing terminal GalNAc of either viral, bacterial or endogenous origin. Recent knowledge about the pathogenesis of IgAN offer new directions for development of causal therapy of the future based on specific affection of Gd-pIgA1 formation, autoantibody production, circulating immune complexes formation or activation of mesangial cells. Which of these approaches will found application in clinical praxis remains to be answered hopefully in close future.
  • Published In

    Author List

  • Raška M; Zadražil J; Horynová MS; Kafková LR; Vráblíková A; Matoušovic K; Mĕstecký J
  • Start Page

  • 63
  • End Page

  • 65
  • Volume

  • 23
  • Issue

  • 2