HIGH BINDING OF IMMUNOGLOBULIN M-KAPPA RHEUMATOID-FACTOR FROM TYPE-IICRYOGLOBULINS TO CELLULAR FIBRONECTIN - A MECHANISM FOR INDUCTION OF IN-SITU IMMUNE-COMPLEX GLOMERULONEPHRITIS

In our previous experimental work we suggested that the frequent nephr itogenicity of type II cryoglobulins could depend on a particular affi nity of the immunoglobulin (Ig) MK rheumatoid factor (RF) component fo r mesangial matrix. Since cellular fibronectin (cFN) in the human kidn ey is mainly represented in glomerular mesangium, we studied the bindi ng capacity to cFN of IgM kappa RFs from type II cryoglobulins compare d with other different monoclonal and polyclonal IgM and IgM RFs. We p urified 13 IgM kappa from human IgM kappa/IgG cryoglobulins, eight mon oclonal IgM from patients with Waldenstrom's macroglobulinemia, nine p olyclonal IgM from normal donors, and eight polyclonal IgM RFs from pa tients with rheumatoid arthritis. Purified IgM were used at the same c oncentration in enzyme-linked immunosorbent assay (ELISA) on cFN-coate d plates. All the cryoglobulin IgM showed high specific binding to cFN while IgM from Waldenstrom's macroglobulinemia, normal IgM, and polyc lonal IgM RFs had low or absent binding. These data were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cFN follo wed by Western blot analysis with purified IgM. The IgM kappa binding to cFN persisted using IgM kappa monomers, and was inhibited by cFN bu t not by plasma FN in a specific inhibition test. Further enzyme-linke d immunosorbent assay studies showed that cryoglobulin IgM kappa RFs a re still able to bind IgG in a dose-dependent manner once linked to so lid-phase cFN. The data suggest that the affinity of cryoglobulin IgM kappa RFs for immobilized cFN could be involved in the particular high nephritogenicity of type II cryoglobulins and might lead to in situ i mmune complex formation, (C) 1996 by the National Kidney Foundation, I nc.