Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89-IgA and IgG-IgA complexes: common mechanisms for distinct diseases

Kidney Int. 2011 Dec;80(12):1352-63. doi: 10.1038/ki.2011.276. Epub 2011 Aug 24.

Abstract

Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA deposits with possible development of secondary IgA nephropathy (IgAN). Since little is known about circulating immune complexes in cases of secondary IgAN, we analyzed IgA-associated parameters in the serum of 32 patients with compensated or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation of IgA1, as well as increased amounts of abnormally glycosylated polymeric IgA1, were detected in the serum of patients with advanced alcoholic cirrhosis. Moreover, aberrant IgA1 formed complexes with IgG and soluble CD89 in serum of patients with advanced alcoholic cirrhosis, similar to those found in primary IgAN. The IgA1 of alcoholic cirrhosis, however, had a modified N-glycosylation, not found in primary IgAN. In patients with alcoholic cirrhosis and IgAN, IgA deposits were associated with CD71 overexpression in mesangial areas, suggesting that CD71 might be involved in deposit formation. Although the IgA1 found in alcoholic cirrhosis bound more extensively to human mesangial cells than control IgA1, they differ from primary IgAN by not inducing mesangial cell proliferation. Thus, abnormally glycosylated IgA1 and soluble CD89-IgA and IgA-IgG complexes, features of primary IgAN, are also present in alcoholic cirrhosis. Hence, common mechanisms appear to be shared by diseases of distinct origins, indicating that common environmental factors may influence the development of IgAN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigen-Antibody Complex*
  • Antigens, CD / blood*
  • Biopsy
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Galactose / blood
  • Galactose / deficiency
  • Glomerulonephritis, IGA / blood
  • Glomerulonephritis, IGA / immunology*
  • Glomerulonephritis, IGA / pathology
  • Glycosylation
  • Humans
  • Immunoglobulin A / blood*
  • Immunoglobulin G / blood*
  • Kidney / immunology*
  • Kidney / pathology
  • Liver Cirrhosis, Alcoholic / blood
  • Liver Cirrhosis, Alcoholic / complications
  • Liver Cirrhosis, Alcoholic / immunology*
  • Liver Cirrhosis, Alcoholic / pathology
  • Male
  • Mesangial Cells / immunology
  • Mesangial Cells / pathology
  • Middle Aged
  • Paris
  • Receptors, Fc / blood*

Substances

  • Antigen-Antibody Complex
  • Antigens, CD
  • Fc(alpha) receptor
  • Immunoglobulin A
  • Immunoglobulin G
  • Receptors, Fc
  • Galactose