Rheumatoid factors reacting with autologous native gamma-G-globulin and joint fluid gamma-G aggregates.

Inflammatory joint fluids from patients with definite or classical rheumatoid arthritis (RA), selected because they precipitated strongly with rheumatoid factors (RF), were examined by sucrose density gradient ultracentrifugation for sedimentation of γG-globulin (γG) and behaviour of RF activity. All contained some γG that sedimented to the γM globulin (γM) zone at pH 7·4; at pH 3·6, γG disappeared from the γM zone. With four joint fluids, no RF activity was detected by cells sensitized with anti-CD Ripley at pH 7·4, but RF activity appeared in the γM zone at pH 3·6. This demonstration of inhibition of RF activity by autologous γG aggregates depended upon the relative amount of RF and γG aggregates in the joint fluid. Two joint fluids which contained γG aggregates and high titre RF activity precipitated with γM RF isolated in high concentration from the corresponding sera. In , RF activity often sedimented faster at pH 7·4 than at pH 3·6, and inhibitors of RF activity against red cells sensitized with various anti-D sera were found in the macroglobulin zone at pH 7·4. These inhibitors were characterized as γG. When aggregate-free I-labelled pooled human γG was mixed with isolated γM RF, 7% of the radioactivity sedimented with RF activity by zone ultracentrifugation at pH 8·0; when mixed with a Waldenström type γM globulin (γM), only 0·2% of the radioactivity was found in the γM zone. Radioimmunoelectrophoresis incidated that I-labelled γG was still bound to γM RF following electrophoresis. These results suggest that native γG is firmly bound to a fraction of RF in some sera. The relationship between these complexes and the 22S complexes of certain rheumatoid sera is discussed.