Schmid F R, Roitt I M, Rocha M J
J Exp Med. 1970 Oct 1;132(4):673-93. doi: 10.1084/jem.132.4.673.
Complement-mediated lysis of sheep erythrocytes coated with optimal concentrations of rabbit IgG hemolysin was inhibited by euglobulin fractions from the sera of patients with seropositive rheumatoid arthritis. That this was due to direct interaction with the IgG coat on the red cell rather than a nonspecific reaction with complement in the fluid phase was confirmed by controls using cells coated with IgM hemolysin. The inhibitory activity was recovered in purified IgM rheumatoid factor preparations and could be absorbed out with insoluble aggregated human IgG. The inhibitory potency of the rheumatoid factors correlated well with their sheep cell agglutination titers. Inhibition was not the result of physical aggregation of the erythrocytes by rheumatoid factor. Kinetic studies were consistent with the view that rheumatoid factor displaces C1q from its binding to IgG. Paradoxically, at suboptimal sensitizing concentrations of IgG hemolysin, rheumatoid factor enhances the fixation of complement. These results can be interpreted on the basis of the blockage of complement fixation by IgG and its replacement by a relatively weak direct fixation by the IgM rheumatoid factor. Thus, the interaction of RF with IgG generates only a limited ability to fix complement which, when contrasted with the fixation at suboptimal concentrations of IgG hemolysin alone, appears as net enhancement; when this is contrasted with fixation occurring with optimal concentrations of IgG, it appears as net inhibition.
血清反应阳性类风湿性关节炎患者血清中的优球蛋白组分可抑制补体介导的、被最佳浓度兔IgG溶血素包被的绵羊红细胞的溶解。用IgM溶血素包被的细胞进行对照实验，证实这是由于与红细胞上的IgG包被直接相互作用，而非与液相中的补体发生非特异性反应。在纯化的IgM类风湿因子制剂中可恢复其抑制活性，且该活性可被不溶性聚集人IgG吸附去除。类风湿因子的抑制效力与其绵羊细胞凝集效价密切相关。抑制作用并非类风湿因子使红细胞发生物理聚集的结果。动力学研究结果与类风湿因子将C1q从其与IgG的结合中置换出来的观点一致。矛盾的是，在IgG溶血素致敏浓度欠佳时，类风湿因子会增强补体的固定。这些结果可以基于IgG对补体固定的阻断以及被IgM类风湿因子相对较弱的直接固定所替代来解释。因此，RF与IgG的相互作用仅产生有限的补体固定能力，与单独使用欠佳浓度IgG溶血素时的固定情况相比，表现为净增强；与使用最佳浓度IgG时的固定情况相比，则表现为净抑制。
