Dataset Information

Galectin-8 in IgA nephritis: decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in non-IgA serum glycoproteins.

ABSTRACT:

Background

Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAc?2-3Gal).

Purpose

The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin with strong affinity for 2-3-sialylated galactosides. Galectins are a family of ?-galactoside-binding proteins; by binding various glycoproteins, they play important roles in the regulation of cellular functions in inflammation and immunity. Hence, an altered binding of IgA to galectin-8 could lead to pathologic immune functions, such as glomerulonephritis.

Methods

Affinity chromatography of serum glycoproteins on the human sialogalactoside-binding lectin galectin-8N permitted quantitation of bound and unbound fractions, including IgA.

Results

Analysis of ~100 IgA nephritis sera showed that the galectin-8N unbound fraction of IgA increased compared to ~100 controls, consistent with the known loss of galactosylation. A subgroup of ~15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA <0.09, not found for any of the controls. Unexpectedly, the galectin-8N-binding fraction of serum glycoproteins other than IgA increased in the sera of IgAN patients but not in controls, suggesting a previously unrecognized change in this disease.

Conclusion

This is the first study that relates a galectin, an endogenous lectin family, to IgA nephritis and thus should stimulate new avenues of research into the pathophysiology of the disease.

SUBMITTER: Carlsson MC

PROVIDER: S-EPMC3305883 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Publications

Galectin-8 in IgA nephritis: decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in non-IgA serum glycoproteins.

Carlsson Michael C MC Bakoush Omran O Tengroth Lotta L Kilsgård Ola O Malmström Johan J Hellmark Thomas T Segelmark Mårten M Leffler Hakon H

Journal of clinical immunology 20111216 2

<h4>Background</h4>Immunoglobulin A nephritis (IgAN) is the most common primary glomerulonephritis worldwide. It is caused by accumulation of IgA1-containing immune complexes in the kidney resulting in renal failure, which is thought to be due to altered glycosylation of IgA with a decrease of 2-3-sialylated galactosides (NeuAcα2-3Gal).<h4>Purpose</h4>The purpose of this study was to analyze whether altered glycosylation of IgA would lead to an altered binding to galectin-8, an endogenous lectin ...[more]

PMID: 22173878

Similar Datasets

Project description:BackgroundLupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management.ObjectiveTo investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN.Patients and methodsLevels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured.ResultsNormalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort.ConclusionGiven its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.

Dataset Information

Galectin-8 in IgA nephritis: decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in non-IgA serum glycoproteins.

Background

Purpose

Methods

Results

Conclusion

Publications

Galectin-8 in IgA nephritis: decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in non-IgA serum glycoproteins.

Similar Datasets

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