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Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2012 Sep; Vol. 23 (9), pp. 1579-87. Date of Electronic Publication: 2012 Aug 16. - Publication Year :
- 2012
-
Abstract
- Mesangial and circulating IgA1 with aberrantly glycosylated hinge region O-glycans characterize IgA nephropathy (IgAN). Unlike healthy individuals, some IgA1 is galactose deficient in patients with IgAN, leaving terminal N-acetylgalactosamine residues in the hinge region exposed. Circulating autoantibodies that recognize such galactose-deficient IgA1 as an autoantigen, or the levels of the autoantigen itself, may allow prediction of disease progression. Here, we analyzed serum samples obtained at diagnosis for autoantigen and autoantibodies from 97 patients with IgAN selected from our prospective cohort according to their absolute renal risk for progression to dialysis or death (0, very low; 1, low; 2, high; 3, very high). We also analyzed samples from controls comprising 30 healthy volunteers and 30 patients with non-IgAN disease. The mean follow-up was 13.8 years. We found that mean serum levels of total autoantigen, normalized IgG autoantibody, and total IgA autoantibody were significantly higher in patients than in the combined controls (all P≤0.01). Furthermore, increasing levels correlated with worse clinical outcomes. In Cox regression and Kaplan-Meier analyses, IgG autoantibody levels ≥1.33 predicted dialysis or death (both P≤0.01). In conclusion, these data suggest that serum levels of IgG and IgA autoantibodies strongly associate with the progression of IgAN nephropathy.
- Subjects :
- Adolescent
Adult
Aged
Autoantigens blood
Biopsy
Case-Control Studies
Cohort Studies
Female
Follow-Up Studies
Glomerulonephritis, IGA pathology
Humans
Immunoglobulin G blood
Kaplan-Meier Estimate
Kidney pathology
Male
Middle Aged
Prospective Studies
Survival Rate
Young Adult
Autoantibodies blood
Disease Progression
Galactose deficiency
Glomerulonephritis, IGA blood
Glomerulonephritis, IGA mortality
Immunoglobulin A blood
Subjects
Details
- Language :
- English
- ISSN :
- 1533-3450
- Volume :
- 23
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 22904352
- Full Text :
- https://doi.org/10.1681/ASN.2012010053