title: Galectin-8 in IgA nephritis: decreased binding of IgA by galectin-8 affinity chromatography and associated increased binding in non-IgA serum glycoproteins.
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).
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section MIG (Microbiology, Immunology, Glycobiology), Department of Laboratory Medicine, Lund University, Sölvegatan 23, 223 62, Lund, Sweden. michael.carlsson@med.lu.se
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carlsson
authors.forename: Omran
authors.initials: O
authors.lastname: Bakoush
authors.forename: Lotta
authors.initials: L
authors.lastname: Tengroth
authors.forename: Ola
authors.initials: O
authors.lastname: Kilsgård
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
authors.forename: Thomas
authors.initials: T
authors.lastname: Hellmark
authors.forename: Mårten
authors.initials: M
authors.lastname: Segelmark
authors.forename: Hakon
authors.initials: H
authors.lastname: Leffler
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D037161:Galectins / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D055815:Young Adult
chemical_list: D037161:Galectins; D006023:Glycoproteins; D007070:Immunoglobulin A; C091991:LGALS8 protein, human