TY - JOUR
T1 - Galectin-8 in IgA Nephritis
T2 - Decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in Non-IgA serum glycoproteins
AU - Carlsson, Michael C.
AU - Bakoush, Omran
AU - Tengroth, Lotta
AU - Kilsgård, Ola
AU - Malmström, Johan
AU - Hellmark, Thomas
AU - Segelmark, Mårten
AU - Leffler, Hakon
N1 - Funding Information:
The work was supported by grants from the Swedish Research Council (Vetenskapsrådet) to HL and JM (project 2008-3356), from the Swedish Foundation for Swedish Research to JM (FFL4), from Swedish Healthcare System (ALF) to TH and MS, and from Region Skåne to HL.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Affinity chromatography
KW - Galectin-8
KW - IgA nephropathy
KW - NeuAcα2-3Gal
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U2 - 10.1007/s10875-011-9618-3
DO - 10.1007/s10875-011-9618-3
M3 - Article
C2 - 22173878
AN - SCOPUS:84863560786
SN - 0271-9142
VL - 32
SP - 246
EP - 255
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
IS - 2
ER -