Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis

Kidney Int. 2011 Jul;80(1):79-87. doi: 10.1038/ki.2011.16. Epub 2011 Feb 16.

Abstract

Serum galactose-deficient immunoglobulin A1 (Gd-IgA1) is an inherited risk factor for adult IgA nephropathy (IgAN). In this paper, we determined the heritability of serum Gd-IgA1 levels in children with IgAN and Henoch-Schönlein purpura nephritis (HSPN), two disorders with clinical phenotypes sharing common pathogenic mechanisms. Serum Gd-IgA1 concentrations were quantified using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay. As a group, 34 children with either disorder (20 with HSPN and 14 with IgAN) had significantly higher Gd-IgA1 levels compared with 51 age- and ethnicity-matched pediatric controls. Serum levels of Gd-IgA1 were also elevated in a large fraction of 54 first-degree relatives of pediatric IgAN and HSPN patients compared with 141 unrelated healthy adult controls. A unilineal transmission of the trait was found in 17, bilineal transmission in 1, and sporadic occurrence in 5 of 23 families when both parents and the patient were analyzed. There was a significant age-, gender-, and household-adjusted heritability of serum galactose-deficient IgA1 estimated at 76% in pediatric IgAN and at 64% in HSPN patients. Thus, serum galactose-deficient IgA1 levels are highly inherited in pediatric patients with IgAN and HSPN, providing support for another shared pathogenic link between these disorders.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aging / blood
  • Aging / immunology
  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Cohort Studies
  • Female
  • Glomerulonephritis, IGA / genetics*
  • Glomerulonephritis, IGA / immunology*
  • Glycosylation
  • Humans
  • IgA Vasculitis / genetics*
  • IgA Vasculitis / immunology*
  • Immunoglobulin A / blood*
  • Immunoglobulin A / chemistry
  • Immunoglobulin A / genetics
  • Male
  • Middle Aged
  • Models, Genetic
  • Nephritis, Hereditary / genetics*
  • Nephritis, Hereditary / immunology*
  • Young Adult

Substances

  • Biomarkers
  • Immunoglobulin A