High binding of immunoglobulin Mκ rheumatoid factor from type II cryoglobulins to cellular fibronectin: A mechanism for induction of in situ immune complex glomerulonephritis?

A. Fornasieri, S. Armelloni, P. Bernasconi, M. Li, C. P. De Septis, R. A. Sinico, G. D'Amico

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Abstract

In our previous experimental work we suggested that the frequent nephritogenicity of type II cryoglobulins could depend on a particular affinity of the immunoglobulin (Ig) Mκ rheumatoid factor (RF) component for mesangial matrix. Since cellular fibronectin (cFN) in the human kidney is mainly represented in glomerular mesangium, we studied the binding capacity to cFN of IgMκ RFs from type II cryoglobulins compared with other different monoclonal and polyclonal IgM and IgM RFs. We purified 13 IgMκ from human IgMκ/IgG cryoglobulins, eight monoclonal IgM from patients with Waldenstrom's macroglobulinemia, nine polyclonal IgM from normal donors, and eight polyclonal IgM RFs from patients with rheumatoid arthritis. Purified IgM were used at the same concentration in enzyme-linked immunosorbent assay (ELISA) on cFN-coated plates. All the cryoglobulin IgM showed high specific binding to cFN while IgM from Waldenstrom's macroglobulinemia, normal IgM, and polyclonal IgM RFs had low or absent binding. These data were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cFN followed by Western blot analysis with purified IgM. The IgMκ binding to cFN persisted using IgMκ monomers, and was inhibited by cFN but not by plasma FN in a specific inhibition test. Further enzyme-linked immunosorbent assay studies showed that cryoglobulin IgMκ RFs are still able to bind IgG in a dose-dependent manner once linked to solid-phase cFN. The data suggest that the affinity of cryoglobulin IgMκ RFs for immobilized cFN could be involved in the particular high nephritogenicity of type II cryoglobulins and might lead to in situ immune complex formation.

Original languageEnglish
Pages (from-to)476-483
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume27
Issue number4
Publication statusPublished - 1996

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Keywords

  • cryoglobulins
  • fibronectin
  • glomerulonephritis
  • immunoglobulin M
  • mesangial matrix
  • Rheumatoid factor

ASJC Scopus subject areas

  • Nephrology

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