IDENTIFICATION OF PATHOGENIC AUTOANTIBODIES

描述：(改编自申请人的摘要)SLE是一种 病因不明的自身免疫性疾病，主要困扰女性 处于生育年龄的。自身抗体的产生，特别是那些 DNA和其他多核苷酸的特异性对 疾病的发病机制。这次调查的总体目标是 是用抗独特型(抗id)来调节自身抗体反应 抗体。在制备小鼠抗小鼠单抗的过程中 对于B细胞淋巴瘤的治疗，研究人员已经 观察到这些试剂中的许多都能识别井上的决定因素 以人类自身抗体为特征。他们提议探索 使用这些抗ID来调节自身抗体产生的可能性 系统性红斑狼疮和相关的自身免疫性疾病。在这项研究的第一阶段，他们 将使用选定的抗ID来亲和纯化假定的自身抗体 从SLE患者的血清中提取。纯化的抗体将是 具有抗原特异性的特征(DNA、多核苷酸等)， 同种异型和电荷，以确认抗-ID识别 致病性自身抗体。肾活检标本也将被检查。 对于沉积的独特型特异性免疫球蛋白的存在。他们 会将候选抗免疫缺陷药物的反应性与其他井- 使用国际专家小组定义的抗独特型试剂 具有抗DNA活性的参考血清。最后，调查人员 建议检测具有自身免疫倾向的小鼠品系的血清 跨种间反应独特型以探索可行性 建立一个动物模型。

DESCRIPTION: (Adapted from the applicant's abstract) SLE is an autoimmune disease of unknown etiology which afflicts, primarily, women of child-bearing age. Production of autoantibodies, particularly those specific for DNA and other polynucleotides are central to the pathogenesis of the disease. The overall objective of this investigation is to regulate autoantibody responses using anti-idiotypic (anti-id) antibodies. During the course of generating murine monoclonal anti- ids for the treatment of B cell lymphoma, the investigators have observed that many of these reagents recognize determinants on well- characterized human autoantibodies. They propose to explore the possibility of using these anti-ids to modulate autoantibody production in SLE and related autoimmuno disorders. In Phase I of this study, they will use selected anti-ids to affinity-purity putative autoantibodies from the sera of patients with SLE. The purified antibodies will be characterized for antigenic specificity (DNA, polynucleotides, etc.), isotype and charge in order to confirm that the anti-ids recognize pathogenic autoantibodies. Renal biopsy specimens will also be examined for the presence of deposited idiotype-specific immunoglobulins. They will compare the reactivity of candidate anti-ids with other well- defined anti-idiotypic reagents using a panel of international reference sera with anti-DNA reactivity. Finally, the investigators propose to examine sera from autoimmune-prone strains of mice for cross-reactive interspecies idiotypes in order to explore the feasibility of establishing an animal model.