Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins.
(2012) In Journal of Clinical Immunology 32(2). p.246-255- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2273974
- author
- Carlsson, Michael LU ; Bakoush, Omran LU ; Tengroth, Lotta ; Kilsgård, Ola ; Malmström, Johan ; Hellmark, Thomas LU ; Segelmark, Mårten LU and Leffler, Hakon LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Immunology
- volume
- 32
- issue
- 2
- pages
- 246 - 255
- publisher
- Springer
- external identifiers
-
- wos:000302615200006
- pmid:22173878
- scopus:84863560786
- pmid:22173878
- ISSN
- 0271-9142
- DOI
- 10.1007/s10875-011-9618-3
- language
- English
- LU publication?
- yes
- id
- 860108c0-08ba-4a73-a570-43118c1c03f5 (old id 2273974)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22173878?dopt=Abstract
- date added to LUP
- 2016-04-04 09:19:04
- date last changed
- 2022-01-29 17:16:58
@article{860108c0-08ba-4a73-a570-43118c1c03f5, 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.}}, author = {{Carlsson, Michael and Bakoush, Omran and Tengroth, Lotta and Kilsgård, Ola and Malmström, Johan and Hellmark, Thomas and Segelmark, Mårten and Leffler, Hakon}}, issn = {{0271-9142}}, language = {{eng}}, number = {{2}}, pages = {{246--255}}, publisher = {{Springer}}, series = {{Journal of Clinical Immunology}}, title = {{Galectin-8 in IgA Nephritis: Decreased Binding of IgA by Galectin-8 Affinity Chromatography and Associated Increased Binding in Non-IgA Serum Glycoproteins.}}, url = {{http://dx.doi.org/10.1007/s10875-011-9618-3}}, doi = {{10.1007/s10875-011-9618-3}}, volume = {{32}}, year = {{2012}}, }