IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells

Kidney Int. 2005 Feb;67(2):504-13. doi: 10.1111/j.1523-1755.2005.67107.x.


Background: Sera of patients with IgA nephropathy (IgAN) contain circulating immune complexes (CIC) composed of galactose-deficient IgA1 complexed with antiglycan antibodies. The role of these CIC in the pathogenesis of IgAN is not known.

Methods: We studied how proliferation of cultured mesangial cells (MC) is affected by CIC prepared from sera of IgAN patients and healthy control subjects using size-exclusion chromatography. CIC-containing fractions were added to serum-starved MC in culture, and cell proliferation was measured using (3)H-thymidine incorporation. The results were confirmed by staining MC using an antibody against proliferating cell nuclear antigen.

Results: The incubation of starved MC with serum fractions with M(r) 800 to 900 kD, rich with galactose-deficient IgA1, stimulated proliferation, while fractions with smaller complexes were inhibitory. Furthermore, CIC-containing larger molecular mass fractions isolated from serum of an IgAN patient collected during an episode of macroscopic hematuria stimulated MC proliferation more than CIC obtained during a subsequent quiescent phase. To examine the role of IgA, we removed IgA1 from serum before fractionation. The resultant IgA1-depleted fractions were devoid of stimulatory IgA-CIC. Sera of IgAN patients were also fractionated after addition of desialylated galactose-deficient polymeric IgA1 to form additional immune complexes. Supplementation with a small quantity of this IgA1 increased cellular proliferation in assays using serum fractions of M(r)>/=800 to 900 kD; uncomplexed IgA1 did not affect MC proliferation significantly. In contrast, supplementation with a larger quantity of this IgA1 inhibited cellular proliferation in assays using serum fractions of M(r) 700 to 800 kD.

Conclusion: Overall, these findings suggest that CIC containing aberrantly glycosylated IgA1 affect proliferation of MC in vitro and, thus, likely play a role in the pathogenesis of IgAN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antigen-Antibody Complex / physiology*
  • Cell Proliferation
  • Female
  • Glomerular Mesangium / cytology*
  • Glomerulonephritis, IGA / etiology
  • Glomerulonephritis, IGA / immunology*
  • Humans
  • Immunoglobulin A / physiology*
  • Immunoglobulin G / physiology
  • Male


  • Antigen-Antibody Complex
  • Immunoglobulin A
  • Immunoglobulin G