Courtenay-Luck N S, Epenetos A A, Winearls C G, Ritter M A
Cancer Res. 1987 Aug 15;47(16):4520-5.
We report that sera from healthy controls, patients with ovarian or lung cancer, and patients with rheumatoid arthritis all contain IgM polyclonal rheumatoid factors which recognize antigenic determinants on murine and to a greater extent human immunoglobulin IgG. The major part of this reactivity is directed against conserved, shared antigenic determinants present on both human and murine IgG. Such antigenicity resides in the protein and not the carbohydrate moiety of IgG, since deglycosylation of the target murine monoclonal antibody did not result in any loss of antibody binding. Studies comparing the binding of polyclonal and monoclonal rheumatoid factors (from patients with rheumatoid arthritis and mixed essential cryoglobulinaemia, respectively) to murine and human IgG show that the antigenic determinants recognized by polyclonal rheumatoid factors are present on both whereas the antigenic determinant recognized by the monoclonal rheumatoid factors is present only on human IgG. Furthermore, patients with rheumatoid arthritis display an elevated human IgM anti-murine immunoglobulin response similar to that seen in cancer patients who have received murine monoclonal antibody therapy. We therefore conclude that, where possible, F(ab')2 fragments of murine monoclonal antibodies should be used for in vivo tumor localization studies to avoid possible immune complex formation, and that patients with rheumatoid arthritis should be considered to be possibly at higher risk of developing immune complex disease, were these rheumatoid factors to bind to the administered murine antibodies in vivo.
我们报告称，健康对照者、卵巢癌或肺癌患者以及类风湿性关节炎患者的血清中均含有IgM多克隆类风湿因子，这些因子可识别鼠源免疫球蛋白IgG上的抗原决定簇，在更大程度上还可识别人类免疫球蛋白IgG上的抗原决定簇。这种反应性的主要部分针对人类和鼠源IgG上存在的保守、共享抗原决定簇。这种抗原性存在于IgG的蛋白质部分而非碳水化合物部分，因为靶标鼠源单克隆抗体的去糖基化并未导致抗体结合能力的任何丧失。比较多克隆和单克隆类风湿因子（分别来自类风湿性关节炎患者和混合性 essential 冷球蛋白血症患者）与鼠源和人类IgG结合情况的研究表明，多克隆类风湿因子识别的抗原决定簇在两者上均存在，而单克隆类风湿因子识别的抗原决定簇仅存在于人类IgG上。此外，类风湿性关节炎患者表现出升高的人类IgM抗鼠源免疫球蛋白反应，这与接受鼠源单克隆抗体治疗的癌症患者中所见的反应相似。因此，我们得出结论，在可能的情况下，应使用鼠源单克隆抗体的F(ab')2片段进行体内肿瘤定位研究，以避免可能的免疫复合物形成，并且如果这些类风湿因子在体内与所施用的鼠源抗体结合，类风湿性关节炎患者应被视为可能有更高的发生免疫复合物疾病的风险。
