Galectin-8 in IgA Nephritis: Decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in Non-IgA serum glycoproteins

Michael C. Carlsson, Omran Bakoush, Lotta Tengroth, Ola Kilsgård, Johan Malmström, Thomas Hellmark, Mårten Segelmark, Hakon Leffler

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 galactosy-lation. A subgroup of ~ 15% of the IgAN patients had a ratio of galectin-8 bound/unbound IgA <0.09, not found for any ofthe 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.

Original languageEnglish
Pages (from-to)246-255
Number of pages10
JournalJournal of Clinical Immunology
Volume32
Issue number2
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Keywords

  • Affinity chromatography
  • Galectin-8
  • IgA nephropathy
  • NeuAcα2-3Gal

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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