title: 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.affiliation: Division of Nephrology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. kk473@columbia.edu
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kiryluk
authors.forename: Zina
authors.initials: Z
authors.lastname: Moldoveanu
authors.forename: John T
authors.initials: JT
authors.lastname: Sanders
authors.forename: T Matthew
authors.initials: TM
authors.lastname: Eison
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.forename: Ali G
authors.initials: AG
authors.lastname: Gharavi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wyatt
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D011695:IgA Vasculitis / Q000235:genetics* / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000276:immunology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A