Sutjita M, Hohmann A, Comacchio R, Boey M L, Bradley J
Department of Clinical Immunology, Flinders Medical Centre, South Australia.
Clin Exp Immunol. 1989 Feb;75(2):211-6.
We have recently produced a series of human monoclonal antibodies reacting with cardiolipin. One of these, H3, a polyspecific IgM/k derived from a normal individual, was used to raise mouse monoclonal antibody to its idiotype. Two anti-idiotypic antibodies, S2.9 (IgG2b) and S2.10 (IgM) were selected for their specific reaction with H3.S2.9 did not react with five other human monoclonal antibodies of IgM/k class despite the fact that these shared some antigen-binding characteristics with H3.S2.9 was able to block the binding of H3 to all of its cross-reactive antigens including cardiolipin, while S2.10 was not. S2.9 was equally efficient in blocking the binding of H3 to three of its cross-reactive antigens, cardiolipin, diphtheria and tetanus toxoids; greater than 90% inhibition could be achieved at an equimolar ratio of H3 to S2.9. The anti-idiotype S2.9 was used to demonstrate the presence of the H3 idiotype in serum. This idiotype was found in amounts greater than that seen in 42 normal individuals, in 30 of 36 patients with systemic lupus erythematosus (SLE), eight of 20 patients with rheumatoid arthritis (RA), 8 of 20 patients with Felty's syndrome as well as 10 of 23 patients with syphilis. Not one of nine patients with drug-induced lupus syndrome had abnormal levels. In patients with SLE and Felty's syndrome there was a good correlation between the amount of anti-cardiolipin antibodies and the amount of H3 idiotype (rs = 0.70 and 0.69 respectively). No such correlation was found in syphilitics or in patients with RA. In patients with SLE the H3 idiotype was present on IgM and IgG anti-cardiolipin antibodies. In 15 of 16 SLE sera with high levels of cardiolipin antibody, S2.9 blocked binding of serum antibodies to cardiolipin by 13-72%, with a mean value of 49%. One patient had a high level of anti-cardiolipin antibody which could not be blocked by S2.9. These results indicate that a mouse monoclonal antibody which reacts with an idiotope in the antigen-binding region of a naturally-occurring phospholipid antibody also defines a common idiotype of anti-cardiolipin antibodies in patients with autoimmune disease.
我们最近制备了一系列与心磷脂反应的人单克隆抗体。其中之一H3是一种源自正常个体的多特异性IgM/κ抗体，被用于制备针对其独特型的小鼠单克隆抗体。选择了两种抗独特型抗体S2.9（IgG2b）和S2.10（IgM），因其与H3有特异性反应。尽管其他5种IgM/κ类人单克隆抗体与H3有一些共同的抗原结合特性，但S2.9与它们不发生反应。S2.9能够阻断H3与其所有交叉反应性抗原（包括心磷脂）的结合，而S2.10则不能。S2.9在阻断H3与其三种交叉反应性抗原（心磷脂、白喉和破伤风类毒素）的结合方面同样有效；在H3与S2.9等摩尔比时，抑制率可超过90%。抗独特型抗体S2.9被用于证明血清中H3独特型的存在。在36例系统性红斑狼疮（SLE）患者中的30例、20例类风湿关节炎（RA）患者中的8例、20例费尔蒂综合征患者中的8例以及23例梅毒患者中的10例中，发现这种独特型的含量高于42例正常个体。9例药物性狼疮综合征患者中无一例异常。在SLE和费尔蒂综合征患者中，抗心磷脂抗体的量与H3独特型的量之间有良好的相关性（rs分别为0.70和0.69）。在梅毒患者或RA患者中未发现这种相关性。在SLE患者中，H3独特型存在于IgM和IgG抗心磷脂抗体上。在16份心磷脂抗体水平高的SLE血清中的15份中，S2.9使血清抗体与心磷脂的结合阻断了13% - 72%，平均值为49%。有1例患者的抗心磷脂抗体水平高，但不能被S2.9阻断。这些结果表明，一种与天然存在的磷脂抗体抗原结合区域中的独特位反应的小鼠单克隆抗体，也确定了自身免疫性疾病患者抗心磷脂抗体的一种共同独特型。
