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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 LU ; Bakoush, Omran LU ; Tengroth, Lotta; Kilsgård, Ola; Malmström, Johan; Hellmark, Thomas LU ; Segelmark, Mårten LU and Leffler, Hakon LU (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)
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author
organization
publishing date
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
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
2012-01-03 19:52:57
date last changed
2016-11-21 10:44:18
@misc{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 &lt;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    = {ARRAY(0x9613df8)},
  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},
  volume       = {32},
  year         = {2012},
}