Cargando…
Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins
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-sialylat...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305883/ https://www.ncbi.nlm.nih.gov/pubmed/22173878 http://dx.doi.org/10.1007/s10875-011-9618-3 |
_version_ | 1782227153182523392 |
---|---|
author | Carlsson, Michael C. Bakoush, Omran Tengroth, Lotta Kilsgård, Ola Malmström, Johan Hellmark, Thomas Segelmark, Mårten Leffler, Hakon |
author_facet | Carlsson, Michael C. Bakoush, Omran Tengroth, Lotta Kilsgård, Ola Malmström, Johan Hellmark, Thomas Segelmark, Mårten Leffler, Hakon |
author_sort | Carlsson, Michael C. |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-011-9618-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3305883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-33058832012-03-22 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. Bakoush, Omran Tengroth, Lotta Kilsgård, Ola Malmström, Johan Hellmark, Thomas Segelmark, Mårten Leffler, Hakon J Clin Immunol Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-011-9618-3) contains supplementary material, which is available to authorized users. Springer US 2011-12-16 2012 /pmc/articles/PMC3305883/ /pubmed/22173878 http://dx.doi.org/10.1007/s10875-011-9618-3 Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article Carlsson, Michael C. Bakoush, Omran Tengroth, Lotta Kilsgård, Ola Malmström, Johan Hellmark, Thomas Segelmark, Mårten Leffler, Hakon Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins |
title | Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins |
title_full | Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins |
title_fullStr | Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins |
title_full_unstemmed | Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins |
title_short | Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins |
title_sort | galectin-8 in iga nephritis: decreased binding of iga by galectin-8 affinity chromatography and associated increased binding in non-iga serum glycoproteins |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305883/ https://www.ncbi.nlm.nih.gov/pubmed/22173878 http://dx.doi.org/10.1007/s10875-011-9618-3 |
work_keys_str_mv | AT carlssonmichaelc galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins AT bakoushomran galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins AT tengrothlotta galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins AT kilsgardola galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins AT malmstromjohan galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins AT hellmarkthomas galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins AT segelmarkmarten galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins AT lefflerhakon galectin8iniganephritisdecreasedbindingofigabygalectin8affinitychromatographyandassociatedincreasedbindinginnonigaserumglycoproteins |