REGULATION OF AUTOANTIBODIES TO RIBOSOMAL P PROTEINS

针对核糖体P蛋白的自身抗体（抗P）对以下具有高度特异性： 系统性红斑狼疮（SLE），并且是潜在致病性的。 我们 我偶然发现，几乎所有健康的成年人都有 然而，这些抗P抗体被抗独特型抗体掩盖 （抗Ids）。 我们假设抗Ids抗P阻止了识别 用抗P抗体检测健康人自体核糖体P蛋白 成年人，他们的功能障碍使抗P能够识别这些自我 蛋白质，从而促进SLE患者的组织损伤。 的目标 这项建议的目的是表征抗P抗体的独特型网络， 健康的成年人、患者及其亲属， 重组抗P抗体的抗Ids。具体目标是： 1)在一个队列中分离和表征抗P抗体的抗Ids， 健康成人; 2)比较SLE患者抗P抗体的独特型， 健康对照; 3)产生抗P的重组抗Ids;和 4)确定SLE患者中是否存在抗P抗体的抗Ids， 亲戚 将纯化来自10名健康成人的抗P的IgG抗Ids， 分析独特位特异性、异质性和结合 特性. 这些抗Ids将用于评估独特型 SLE患者和健康人抗P抗体的相似性 对照 重组噬菌体抗体系统（Pharmacia）将在 用于产生抗P. SLE患者的重组抗Ids， 将评价抗P抗体及其近亲的抗Ids抗体 反P 拟议调查的结果应有助于了解 抗Id抗体在健康和疾病中对抗P的调节。 这些知识将有助于制定新的战略， 防止抗P抗体中抗P自身抗体的自我识别 自身免疫 将产生重要的工具， 机制和分子免疫学研究。 此外，结果可能具有普遍适用性， 自身抗体系统也是如此。如果健康成人的抗Ids抗体与 从患者体内分离抗P抗体，并产生重组抗Ids， 抗-P，那么这些抗-Ids可以在治疗上用于控制 表达，从而，抗P抗体在患者中的临床后遗症。

Autoantibodies to ribosomal P proteins (anti-P) are highly specific for systemic lupus erythematosus (SLE), and are potentially pathogenic. We serendipitously observed that virtually all healthy adults also possess anti-P. These anti-P, however, are masked by anti-idiotypic antibodies (anti-Ids). We hypothesize that anti-Ids to anti-P prevent recognition of autologous ribosomal P proteins by anti-P antibodies in healthy adults, and that their dysfunction allows anti-P to recognize these self proteins, and thereby, promote tissue injury in SLE patients. The goals of this proposal are to characterize the idiotype network for anti-P in healthy adults, patients, and their relatives, and to generate recombinant anti-Ids to anti-P. The specific aims are to: 1) isolate and characterize the anti-Ids to anti-P in a cohort of healthy adults; 2) compare the idiotypes of anti-P antibodies from SLE patients and healthy controls; 3) generate recombinant anti-Ids to anti-P; and 4) determine if anti-Ids to anti-P exist in SLE patients and their relatives. IgG anti-Ids to anti-P from ten healthy adults will be purified and analyzed for idiotope specificity, heterogeneity, and binding properties. These anti-Ids will be used to evaluate idiotypic similarities among anti-P antibodies from SLE patients and healthy controls. The recombinant phage antibody system (Pharmacia) will be used to generate recombinant anti-Ids to anti-P. SLE patients with anti-P and their consanguineous relatives will be evaluated for anti-Ids to anti-P. Results from the proposed investigations should provide insights into the regulation of anti-P by anti-Id antibodies in health and disease. This knowledge will allow new strategies to be developed that will prevent self-recognition by anti-P autoantibodies in anti-P autoimmunity. Important tools will be generated that will allow future mechanistic and molecular immunologic studies to be devised. Furthermore, the results may have general applicability to their autoantibody systems as well. If anti-Ids from healthy adults react with anti-P from patients, and recombinant anti-Ids are generated that mask anti-P, then these anti-Ids may be useful therapeutically to control the expression, and thereby, the clinical sequelae of anti-P in patients.