IgA glycosylation and immune complex formation in IgAN

Semin Immunopathol. 2021 Oct;43(5):669-678. doi: 10.1007/s00281-021-00883-8. Epub 2021 Sep 27.

Abstract

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. This disease, discovered in 1968, is characterized by IgA-IgG glomerular immunodeposits with a mesangial pattern. It is thought that these immunodeposits originate from the immune complexes formed in the circulation. It is hypothesized that the pathogenesis of IgAN is driven by aberrant glycoforms of IgA1 (galactose-deficient IgA1, Gd-IgA1). Gd-IgA1, in genetically susceptible individuals, represents the initiating factor for the formation of circulating immune complexes due to its recognition by IgG autoantibodies and the subsequent formation of pathogenic IgA1-IgG immune complexes. Complement activation through alternative and/or lectin pathways is likely playing an important role in the pathogenic properties of these complexes and may further upregulate local inflammatory responses and glomerular injury.

Keywords: APRIL; Aberrantly glycosylated IgA1; IgG autoantibodies; Immune complex; Mucosal immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigen-Antibody Complex*
  • Glomerulonephritis, IGA*
  • Glycosylation
  • Humans
  • Immunoglobulin A / metabolism
  • Kidney Glomerulus / metabolism

Substances

  • Antigen-Antibody Complex
  • Immunoglobulin A