Down-regulation of core 1 beta1,3-galactosyltransferase and Cosmc by Th2 cytokine alters O-glycosylation of IgA1

Nephrol Dial Transplant. 2010 Dec;25(12):3890-7. doi: 10.1093/ndt/gfq325. Epub 2010 Jun 15.


Background: Patients with IgA nephropathy (IgAN) have an increased amount of abnormally O-glycosylated IgA1 in circulation, in glomerular deposits and produced by tissue cells in vitro. Although increased production of Th2 cytokines by peripheral blood lymphocytes and a functional abnormality of core 1 β1,3-galactosyltransferase (C1β3Gal-T) have been proposed as mechanisms underlying pathogenesis of IgAN, they are still obscure and are not connected.

Methods: To clarify the effect of T-cell cytokines, we analysed the mRNA levels of C1β3Gal-T and its molecular chaperone Cosmc, C1β3Gal-T activity and subsequent O-glycosylation of IgA1 in a human B-cell line stimulated with these cytokines. The surface IgA1-positive human B-cell line was cultured with recombinant human IFN-γ, IL-2, IL-4 or IL-5. The production and glycosylation of IgA1 were determined by sandwich ELISA and enzyme-linked lectin binding assay, respectively. The mRNA levels of C1β3Gal-T and Cosmc were quantitatively measured by real-time PCR. C1β3Gal-T activity was analysed using high-performance liquid chromatography.

Results: IgA1 production by IL-4-stimulated cells was significantly higher than controls or after IFN-γ or IL-5. The terminal glycosylation of secreted IgA1 was altered in response to IL-4. IL-4 stimulation significantly decreased the mRNA levels of both C1β3Gal-T and Cosmc and of C1β3Gal-T activity. IL-4 stimulation was clearly blocked by recombinant human IL-4 soluble receptor.

Conclusions: It appears that Th2 cytokine IL-4 may play a key role in controlling glycosylation of the IgA1 hinge region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / metabolism
  • Cytokines / pharmacology*
  • Down-Regulation / physiology*
  • Galactosyltransferases / metabolism
  • Glomerulonephritis, IGA / metabolism
  • Glomerulonephritis, IGA / pathology
  • Glycosylation / drug effects
  • Humans
  • Immunoglobulin A / metabolism*
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Molecular Chaperones / metabolism*
  • RNA, Messenger / metabolism


  • C1GALT1C1 protein, human
  • Cytokines
  • Immunoglobulin A
  • Molecular Chaperones
  • RNA, Messenger
  • Interleukin-4
  • Galactosyltransferases
  • glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase