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Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy.
- Source :
-
Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2011 Aug; Vol. 6 (8), pp. 1903-11. Date of Electronic Publication: 2011 Jul 22. - Publication Year :
- 2011
-
Abstract
- Background and Objectives: We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1).<br />Design, Setting, Participants, & Measurements: Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA).<br />Results: Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR.<br />Conclusions: Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.
- Subjects :
- Adolescent
Biomarkers blood
Case-Control Studies
Disease Progression
Enzyme-Linked Immunosorbent Assay
Female
Galactose deficiency
Glomerulonephritis, IGA blood
Glomerulonephritis, IGA diagnosis
Glycation End Products, Advanced blood
Glycosylation
Humans
Italy
Least-Squares Analysis
Linear Models
Male
Predictive Value of Tests
Serum Albumin analysis
Time Factors
United States
Up-Regulation
Young Adult
Galactose blood
Glomerulonephritis, IGA metabolism
Immunoglobulin A blood
Oxidative Stress
Subjects
Details
- Language :
- English
- ISSN :
- 1555-905X
- Volume :
- 6
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Clinical journal of the American Society of Nephrology : CJASN
- Publication Type :
- Academic Journal
- Accession number :
- 21784819
- Full Text :
- https://doi.org/10.2215/CJN.11571210