Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins.

Summary, in English

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.

• Författare: Michael Carlsson; Omran Bakoush; Lotta Tengroth; Ola Kilsgård; Johan Malmström; Thomas Hellmark; Mårten Segelmark; Hakon Leffler
• Avdelning/ar: Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG; Njurmedicin; Autoimmunitet och njursjukdomar
• Publiceringsår: 2012
• Språk: Engelska
• Sidor: 246-255
• Publikation/Tidskrift/Serie: Journal of Clinical Immunology
• Volym: 32
• Issue: 2
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/22173878?dopt=Abstract; http://dx.doi.org/10.1007/s10875-011-9618-3
• Dokumenttyp: Artikel i tidskrift
• Förlag: Springer
• Ämne: Immunology in the medical area
• Status: Published
• Forskningsgrupp: Autoimmunity and kidney diseases
• ISBN/ISSN/Övrigt: ISSN: 0271-9142