O- and N-glycosylation of serum immunoglobulin A is associated with IgA nephropathy and glomerular function.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and is a leading cause of renal failure. The disease mechanisms are not completely understood, but a higher abundance of galactose-deficient IgA is recognized to play a crucial role in IgAN pathogenesis. Although both types of human IgA (IgA1 and IgA2) have several N-glycans as post-translational modification, only IgA1 features extensive hinge-region O-glycosylation. IgA1 galactose deficiency on the O-glycans is commonly detected by a lectin-based method. To date, limited detail is known about IgA O- and N-glycosylation in IgAN. METHODS: To gain insights into the complex O- and N-glycosylation of serum IgA1 and IgA2 in IgAN, we used liquid chromatography-mass spectrometry (LC-MS) for the analysis of tryptic glycopeptides of serum IgA from 83 patients with IgAN and 244 age- and sex-matched healthy controls. RESULTS: Multiple structural features of N-glycosylation of IgA1 and IgA2 were associated with IgAN and glomerular function in our cross-sectional study. These features included differences in galactosylation, sialylation, bisection, fucosylation, and N-glycan complexity. Moreover, IgA1 O-glycan sialylation was associated with both the disease and glomerular function. Finally, glycopeptides were a better predictor of IgAN and glomerular function than galactose-deficient IgA1 levels measured by lectin-based ELISA. CONCLUSIONS: Our high-resolution data suggest that IgA O- and N-glycopeptides are promising targets for future investigations on the pathophysiology of IgAN and as potential noninvasive biomarkers for disease prediction and deteriorating kidney function.
Date Issued
2021-09-01
Date Acceptance
2021-05-05
Citation
Journal of the American Society of Nephrology, 2021, 32 (9), pp.1-12
ISSN
1046-6673
Publisher
American Society of Nephrology
Start Page
1
End Page
12
Journal / Book Title
Journal of the American Society of Nephrology
Volume
32
Issue
9
Copyright Statement
© 2021 by the American Society of Nephrology
Sponsor
Wellcome Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34127537
PII: ASN.2020081208
Grant Number
212252/Z/18/Z
Subjects
IgA nephropathy
glycosylation
immunoglobulin
mass spectrometry
posttranslational modification
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-06-14