Sultan Y, Rossi F, Kazatchkine M D
Proc Natl Acad Sci U S A. 1987 Feb;84(3):828-31. doi: 10.1073/pnas.84.3.828.
Plasma samples obtained from a patient 6 wk, 6 months, and 4 yr after recovery from anti-VIII:C (anti-hemophilic factor, where VIII:C = factor VIII procoagulant activity) autoimmune disease were found to contain antibodies that inhibited anti-VIII:C activity in the patient's prerecovery plasma and in the plasma of two other patients with anti-VIII:C autoantibodies. F(ab')2 fragments from postrecovery IgG suppressed anti-VIII:C activity in F(ab')2 fragments from prerecovery IgG within a narrow range of molar ratios. Anti-VIII:C activity in F(ab')2 autoantibodies was also inhibited by F(ab')2 fragments from polyspecific therapeutic immunoglobulins prepared from a large pool of normal donors (IVIg). IgG from prerecovery plasma bound to F(ab')2 from postrecovery IgG and to F(ab')2 from IVIg, as assessed by ELISA. Affinity chromatography experiments demonstrated that F(ab')2 from postrecovery IgG preferentially bound anti-VIII:C antibodies among F(ab')2 fragments from prerecovery plasma containing anti-VIII:C autoantibodies. F(ab')2 from prerecovery plasma bound in higher amounts to postrecovery F(ab')2 than to IVIg. Insolubilized F(ab')2 fragments from postrecovery plasma also bound F(ab')2 fragments prepared from the plasma of another patient with anti-VIII:C autoimmune disease, although in lesser amounts than the patient's own prerecovery anti-VIII:C F(ab')2 antibodies. These observations suggest that human anti-VIII:C autoantibodies share idiotypic determinants and that spontaneous recovery from anti-VIII:C autoimmune disease occurs through idiotypic suppression of autoantibodies. In patients who recover from autoimmune disease and in patients in whom autoantibodies have been suppressed by infusions of IVIg, antiidiotypic antibodies, possibly by providing internal images of the antigen, may have shifted the immune system toward the steady-state equilibrium that prevents autoimmunity in normal individuals.
从一名抗VIII:C（抗血友病因子，其中VIII:C = 凝血因子VIII促凝活性）自身免疫性疾病康复后6周、6个月和4年的患者获取的血浆样本，被发现含有抗体，这些抗体抑制该患者康复前血浆以及另外两名患有抗VIII:C自身抗体患者血浆中的抗VIII:C活性。康复后IgG的F(ab')2片段在狭窄的摩尔比范围内抑制康复前IgG的F(ab')2片段中的抗VIII:C活性。来自多特异性治疗性免疫球蛋白（由大量正常供体的血浆制备，即静脉注射免疫球蛋白，IVIg）的F(ab')2片段也抑制F(ab')2自身抗体中的抗VIII:C活性。通过ELISA评估，康复前血浆中的IgG与康复后IgG的F(ab')2以及IVIg的F(ab')2结合。亲和层析实验表明，在含有抗VIII:C自身抗体的康复前血浆的F(ab')2片段中，康复后IgG的F(ab')2优先结合抗VIII:C抗体。康复前血浆的F(ab')2与康复后F(ab')2的结合量高于与IVIg的结合量。康复后血浆的不溶性F(ab')2片段也结合了另一名患有抗VIII:C自身免疫性疾病患者血浆制备的F(ab')2片段，尽管结合量少于该患者自身康复前的抗VIII:C F(ab')2抗体。这些观察结果表明，人类抗VIII:C自身抗体共享独特型决定簇，并且抗VIII:C自身免疫性疾病的自发康复是通过自身抗体的独特型抑制发生的。在从自身免疫性疾病康复的患者以及通过输注IVIg抑制自身抗体的患者中，抗独特型抗体可能通过提供抗原的内部影像，使免疫系统朝着防止正常个体发生自身免疫的稳态平衡转变。
