Noncognate binding to histones of IgG from patients with idiopathic systemic lupus erythematosus

The mechanism of attachment of circulating immune complexes (CIC) to glomerular basement membranes (GBM) has not yet been elucidated. Since it has been proposed that histone may be the ligand between GBM and DNA/anti-DNA CIC, we explored by ELISA and Western blots the nature of the interaction of IgG with histone on solid phase. Cognate binding of IgG anti-histone antibody was characteristically dependent on in its F(ab')(2) fragment and was inhibited by free histone. On the other hand, heat-aggregated IgG, a model for CIC, and IgG from most patients with idiopathic SLE had a characteristic noncognate binding behavior to histone: it was dependent on Fcgamma rather than on the F(ab')(2) fragment and was not effectively inhibited by free histones. Also, binding to histone of in vitro generated DNA/anti-DNA immune complexes was not dependent on DNA as a histone ligand, but on Fcgamma. Finally, there was good agreement between the binding of this IgG to histone and to C1q. We concluded that: (1) altered IgG and/or CIC bind to solid-phase-attached histone primarily through their Fcgamma and (2) CIC may mimic IgG antihistone antibodies in solid-phase immunoassays.