Dilution Dependent Autoinhibition of Agglutination in Rheumatoid Arthritis Sera and Rabbit Anti-Human γG Antisera

Abstract

Summary Sera from patients with rheumatoid arthritis were titrated with human γG-immunoglobulin coated tanned sheep cells at six cell concentrations ranging from 0.125% to 2.0%. Double logarithmic plots of titer vs. cell concentration were linear. Fifteen of 21 cases (71%) yielded slopes greater than -1.0 reflecting an abnormally large decrease in titer with increasing cell concentration. Previous work (3) has shown that the abnormal titer decreases were due to an autoinhibitory component in the patient's own γG. In the present study it was found that increased slopes were independent of RF titer, duration of disease, or age of patient. Increased slopes were associated with a greater frequency of diagnosis of rheumatoid arthritis as compared to nonrheumatoid disease. Comparison of sera and synovial fluids derived from the same individual revealed identical slope values even when RF titers of both fluids differed appreciably. Certain sera when studied with human and rabbit γG coated cells revealed elevated slopes in both test systems; others, only in the human system. Block titration of rabbit antisera against purified human γG yielded normal -1.0 slopes in the initial bleedings. However, antisera obtained 3 to 4 weeks after initial immunization showed elevated slopes. This was true when agglutination titers were increasing, as well as when such titers were decreasing. It is suggested that in RF sera at least, elevated slopes are due to a dilution dependent autoinhibition of agglutination which arises from the interaction between at least part of the patient's rheumatoid factor with his autologous γG.