Fehr K, Velvart M, Böni A, Watanabe H, Spycher M A, Rüttner J R
Ann Rheum Dis. 1976 Apr;35(2):85-96. doi: 10.1136/ard.35.2.85.
Intra-articularly injected autologous Fab2 produced from IgG by homologous cathepsin D induces in animals not given prior immunization acute synovitis after 1 and 3 injections, acute synovitis after 6 injections, and chronic synovitis after 12 injections. Histologically, the chronic synovitis is similar to synovitis in rheumatoid arthritis (RA). In the joint, cathepsin D Fab2 appears to act as a fairly strong antigen. Evidence for this is provided by the infiltration of large numbers of polymorphonuclear leucocytes, the marked phagocytic activity of the exudate leucocytes and tissue phagocytes, and the stimulation of the synthesis of specific antibodies (homoreactants) in the synovial plasma cells. The immediate action of injected Fab2 suggests that it forms biologically active immune complexes with homoreactants already present. These complexes are phagocytosed, the homoreactants being demonstrable immunohistochemically in inclusions of the exudate and tissue phagocytes. In addition, the local synthesis of antigammaglobulins of rheumatoid factor type is also induced. These react with heat-aggregated homologous as well as human IgG and are likewise found in inclusions in the exudate and tissue phagocytes. In the serum of the animals the titre of rheumatoid factor-like antigammaglobulins increases to an extent depending on the number of injections given. These histochemical and serological findings show striking parallels with the findings in human RA.
通过同源组织蛋白酶D从IgG产生的关节内注射自体Fab2，在未预先免疫的动物中，注射1次和3次后会诱发急性滑膜炎，注射6次后会诱发急性滑膜炎，注射12次后会诱发慢性滑膜炎。从组织学上看，慢性滑膜炎与类风湿性关节炎（RA）中的滑膜炎相似。在关节中，组织蛋白酶D Fab2似乎起着相当强的抗原作用。大量多形核白细胞的浸润、渗出液白细胞和组织吞噬细胞明显的吞噬活性，以及滑膜浆细胞中特异性抗体（自身反应物）合成的刺激，都为此提供了证据。注射的Fab2的即时作用表明它与已存在的自身反应物形成了生物活性免疫复合物。这些复合物被吞噬，自身反应物在渗出液和组织吞噬细胞的包涵体中可通过免疫组织化学方法检测到。此外，还诱导了类风湿因子型抗球蛋白的局部合成。这些抗球蛋白与热聚集的同源以及人IgG发生反应，同样也存在于渗出液和组织吞噬细胞的包涵体中。在动物血清中，类风湿因子样抗球蛋白的滴度会根据注射次数的多少而有所升高。这些组织化学和血清学发现与人类RA的发现有着惊人的相似之处。
