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

Krzysztof Kiryluk; Zina Moldoveanu; John T. Sanders; T. Matthew Eison; Hitoshi Suzuki; Bruce A. Julian; Jan Novak; Ali G. Gharavi; Robert J. Wyatt

doi:10.1038/ki.2011.16

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

Krzysztof Kiryluk, Zina Moldoveanu, John T. Sanders, T. Matthew Eison, Hitoshi Suzuki, Bruce A. Julian, Jan Novak, Ali G. Gharavi, Robert J. Wyatt

Research output: Contribution to journal › Article › peer-review

205 Scopus citations

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.

Original language	English
Pages (from-to)	79-87
Number of pages	9
Journal	Kidney International
Volume	80
Issue number	1
DOIs	https://doi.org/10.1038/ki.2011.16
State	Published - Jul 2011
Externally published	Yes

Keywords

Henoch-Schö nlein purpura
IgA nephropathy
genetic renal disease
glomerular disease
glomerulonephritis

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10.1038/ki.2011.16

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@article{b09e138ddf6f4b9e9da918a16206dd8d,

title = "Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Sch{\"o}nlein 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-Sch{\"o}nlein 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.",

keywords = "Henoch-Sch{\"o} nlein purpura, IgA nephropathy, genetic renal disease, glomerular disease, glomerulonephritis",

author = "Krzysztof Kiryluk and Zina Moldoveanu and Sanders, {John T.} and Eison, {T. Matthew} and Hitoshi Suzuki and Julian, {Bruce A.} and Jan Novak and Gharavi, {Ali G.} and Wyatt, {Robert J.}",

note = "Funding Information: We thank our patients and their families for participation in this study. KK was supported by the Daland Fellowship from the American Philosophical Society and by Grant Number KL2 RR024157 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. RJW, JN, BAJ, ZM, and AGG were supported by Grant Number DK082753 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). JTS was supported by a fellowship training award from the National Kidney Foundation. We also acknowledge other grants from NIDDK supporting their research of IgAN: DK078244, DK080301, DK075868, DK083663, DK071802, and DK077279. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NCRR, NIDDK, or NIH. ",

year = "2011",

month = jul,

doi = "10.1038/ki.2011.16",

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journal = "Kidney International",

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T1 - Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis

AU - Kiryluk, Krzysztof

AU - Moldoveanu, Zina

AU - Sanders, John T.

AU - Eison, T. Matthew

AU - Suzuki, Hitoshi

AU - Julian, Bruce A.

AU - Novak, Jan

AU - Gharavi, Ali G.

AU - Wyatt, Robert J.

N1 - Funding Information: We thank our patients and their families for participation in this study. KK was supported by the Daland Fellowship from the American Philosophical Society and by Grant Number KL2 RR024157 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. RJW, JN, BAJ, ZM, and AGG were supported by Grant Number DK082753 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). JTS was supported by a fellowship training award from the National Kidney Foundation. We also acknowledge other grants from NIDDK supporting their research of IgAN: DK078244, DK080301, DK075868, DK083663, DK071802, and DK077279. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NCRR, NIDDK, or NIH.

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

KW - Henoch-Schö nlein purpura

KW - IgA nephropathy

KW - genetic renal disease

KW - glomerular disease

KW - glomerulonephritis

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DO - 10.1038/ki.2011.16

M3 - Article

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SN - 0085-2538

VL - 80

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JO - Kidney International

JF - Kidney International

IS - 1

ER -

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

Abstract

Keywords

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