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

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.

• Authors: Krzysztof Kiryluk, Zina Moldoveanu, John T Sanders, T Matthew Eison, Hitoshi Suzuki, Bruce A Julian, Jan Novak, Ali G Gharavi, Robert J Wyatt
• Journal: Kidney international (Kidney Int) Vol. 80 Issue 1 Pg. 79-87 (Jul 2011) ISSN: 1523-1755 [Electronic] United States
• PMID: 21326171 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Immunoglobulin A

Topics

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