Hay F C, Jones M G, Bond A, Soltys A J
St. George's Hospital Medical School, London, United Kingdom.
Clin Orthop Relat Res. 1991 Apr(265):54-62.
New information regarding rheumatoid factors (RFs) indicates that the RFs synthesized in synovium and lymphoid tissues of patients with rheumatoid arthritis (RA) are different from monoclonal and nonspecific RFs associated with other inflammatory states. The characteristics of RF associated with RA are as follows. They are of all Ig isotypes (not just IgM), indicating T-cell participation in antibody maturation. They have higher avidity for human IgG than for rabbit IgG. They use the human germline heavy-chain variable region (VH) gene VHIII more frequently than other VH genes, and light chains from multiple families. (In contrast, monoclonal RFs use predominantly VH1 and very commonly the V kappa IIIb germline gene HUMkv325). RA IgG is somatically mutated. (In contrast, monoclonal RFs use unmutated germline Ig genes). This suggests they are matured by stimulation either with specific antigens or other activation signals such as cytokines. They are abnormally glycosylated. In general, during periods of disease activity in adult and juvenile RA, a galactose is missing from the Fc of the IgG molecule, leaving an empty "pocket" between the C gamma 2 domains of heavy chains. The IgG RFs self-associate. This may result at least in part when galactose on the F(ab')2 portion of one IgG molecule fills the empty pocket in the Fc of another Ig molecule. Self-association forms immune complexes capable of fixing complement and probably of causing joint damage and vasculitis.
关于类风湿因子（RFs）的新信息表明，类风湿关节炎（RA）患者滑膜和淋巴组织中合成的RFs与其他炎症状态相关的单克隆和非特异性RFs不同。与RA相关的RFs具有以下特征。它们属于所有Ig同种型（不仅仅是IgM），表明T细胞参与抗体成熟。它们对人IgG的亲和力高于对兔IgG的亲和力。它们比其他VH基因更频繁地使用人类种系重链可变区（VH）基因VHIII，以及来自多个家族的轻链。（相比之下，单克隆RFs主要使用VH1，并且非常常见地使用VκIIIb种系基因HUMkv325）。RA IgG发生体细胞突变。（相比之下，单克隆RFs使用未突变的种系Ig基因）。这表明它们通过特定抗原或其他激活信号（如细胞因子）的刺激而成熟。它们存在异常糖基化。一般来说，在成人和青少年RA的疾病活动期，IgG分子的Fc段缺少一个半乳糖，在重链的Cγ2结构域之间留下一个空的“口袋”。IgG RFs会自我缔合。当一个IgG分子的F(ab')2部分上的半乳糖填充另一个Ig分子Fc段中的空口袋时，这可能至少部分导致自我缔合。自我缔合形成能够固定补体并可能导致关节损伤和血管炎的免疫复合物。
