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

• Published in: Kidney international Vol. 80; no. 1; pp. 79 - 87
• Main Authors: Kiryluk, Krzysztof, Moldoveanu, Zina, Sanders, John T., Eison, T. Matthew, Suzuki, Hitoshi, Julian, Bruce A., Novak, Jan, Gharavi, Ali G., Wyatt, Robert J.
• Format: Journal Article
• Language: English
• Published: Basingstoke Elsevier Inc 01-07-2011; Nature Publishing Group; Elsevier Limited
• Subjects: Adolescent; Adult; Aging - blood; Aging - immunology; Biological and medical sciences; Biomarkers - blood; Case-Control Studies; Child; Cohort Studies; Dermatology; Female; genetic renal disease; glomerular disease; Glomerulonephritis; Glomerulonephritis, IGA - genetics; Glomerulonephritis, IGA - immunology; Glycosylation; Henoch–Schönlein purpura; Humans; IgA nephropathy; Immunoglobulin A - blood; Immunoglobulin A - chemistry; Immunoglobulin A - genetics; Male; Medical sciences; Middle Aged; Models, Genetic; Nephritis, Hereditary - genetics; Nephritis, Hereditary - immunology; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Purpura, Schoenlein-Henoch - genetics; Purpura, Schoenlein-Henoch - immunology; Vascular disorders of the skin; Young Adult; IgA nephropathy; glomerular disease; glomerulonephritis; genetic renal disease; Henoch–Schönlein purpura; Glomerulonephritis; Pediatrics; Skin disease; Nephrology; Nephritis; Diseases of the osteoarticular system; Cardiovascular disease; Urology; Vascular disease; Henoch-Schönlein purpura; IgA glomerular nephropathy; Child; Human; Kidney disease; Immunopathology; Urinary system disease; Glycosylation; Hereditary; IgA1; Genetic disease; Renal failure; Capillary vessel disease
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.2011.16

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.