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 (NeuAcα2-3Gal).

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 β-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.

• Authors: Michael C Carlsson, Omran Bakoush, Lotta Tengroth, Ola Kilsgård, Johan Malmström, Thomas Hellmark, Mårten Segelmark, Hakon Leffler
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 32 Issue 2 Pg. 246-55 (Apr 2012) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 22173878 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Galectins
• Glycoproteins
• Immunoglobulin A
• LGALS8 protein, human

Topics

• Adult
• Aged
• Disease Progression
• Female
• Galectins (metabolism)
• Glomerulonephritis, IGA (immunology, metabolism)
• Glycoproteins (blood, immunology, metabolism)
• Humans
• Immunoglobulin A (immunology, metabolism)
• Male
• Middle Aged
• Protein Binding
• Young Adult