DETECTION OF CIRCULATING ANTIGEN-ANTIBODY COMPLEXES BY THEIR INHIBITORY EFFECT ON AGGLUTINATION OF IGG-COATED PARTICLES BY RHEUMATOID-FACTOR OR CLQ

Abstract

The agglutination of Ig [immunoglobulin]-coated particles by human RF [rhematoid factor] or C1q [q fragment of the 1st complement component] can be inhibited by Ig aggregates or AgAb [antigen-antibody] complexes. The effect of Ig class was studied by means of agarose-linked human monoclonal Ig. RF was inhibited by all subclasses of IgG and IgA but not by IgM, whereas C1q reacted with IgM, IgG3 and IgG1. Heat-aggregated IgG3 was fractionated by gel-filtration on Ultrogel. Inhibition was restricted to certain fractions of aggregates, i.e., .**GRAPHIC**. [IgG3 possessing 7 monomeric units per aggregate] and .**GRAPHIC**. for RF, and .**GRAPHIC**. and .**GRAPHIC**. for C1q. In a precipitin curve experiment, RF was inhibited by soluble complexes over an extended range of AgAb ratios, the inactivation of C1q being limited to complexes with 2-5 times antigen excess. Inhibiting factors were found in patients with various diseases and, at low titers, in 22% of healthy people. In 27% of patients'' sera, the inhibitors were demonstrable by C1q only after removal of endogenous RF by adsorption on insolubilized IgG. In several patients, endogenous agglutinating activity and direct inhibitory activity tended to alternate during the course of the disease. Sera from various patients were filtrated on Ultrogel, and the elution was monitored by immunoassay of IgA, IgM and IgG, and by the 2 inhibition tests. The inhibiting factors were distributed over several peaks which only partially coincided with the elution profiles of IgG and IgM.