IMMUNOGENETIC STUDIES OF COLLAGEN ARTHRITIS

胶原关节炎的免疫遗传学研究

• 批准号: 3155883
• 负责人: Marie M. Griffiths
• 金额: $ 11.37万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-04-01 至 1990-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3155883
• 关键词: T lymphocyte; autoimmune disorder; cell cell interaction; cellular immunity; collagen; collagenase; disease /disorder model; enzyme linked immunosorbent assay; genetic regulation; humoral immunity; hybridomas; immunogenetics; immunoregulation; interferons; interleukin 2; laboratory rat; leukocyte activation /transformation; monoclonal antibody; rheumatoid arthritis; tissue /cell culture

Type II collagen-induced arthritis (CIA) is an experimentally induced and genetically controlled autoimmune model of chronic, peripheral arthritis. Multiple genes are involved. An inbred rat colony of susceptible and resistant, congenic, prototype and recombinant rat strains is being used to elucidate several parameters of CIA that directly relate to joint inflammation in rheumatic disease patients. 1) The existence of a genetic relatedness between susceptibility to arthritis and to autoimmune diseases is being questioned by comparative strain analysis of susceptibility to CIA and other experimental models of arthritis. 2) To determine if differences in susceptibility to CIA are related to differences in specificity of the immune response to type II collagen, antisera from resistant and susceptible strains are being analyzed (by ELISA) for relative reactivity with isolated helical cyanogen-bromide (CB) peptides of rat collagen (II). 3) Strains of the RT1 haplotype are low responders and CIA-resistant. Intra-RT1 recombinants will be used to identify the RT1 subregion that controls anti-collagen immune reactivity. To test for collagen-specific T-suppressor cells, non-arthritogenic adjuvants will be used during immunization. 4) The existence of specific "arthritogenic" regions of the collagen molecule is proposed and will be tested in two approaches: a) immunization with individual CB peptides prepared biochemically from heterologous type II collagens; b) use of hybridoma technology to prepare a panel of monoclonal antibodies reactive with rat collagen (II) which will be tested for ability to passively transfer arthritis to unimmunized rats. 5) Tissue culture techniques are being used to investigate the interaction of synovial cells, collagen, and immune T-cells with emphasis on the roles of interferon and interleukins. Genetic differences between susceptible and resistant rats, in the production of or response to these immunomodulators will be questioned.

II型胶原诱导性关节炎(CIA)是一种实验诱导和 慢性周围性关节炎的基因控制的自身免疫模型。 这涉及到多个基因。一群近亲繁殖的易受感染和 耐药、同源、原型和重组大鼠品系正被用于 阐明与关节直接相关的CIA的几个参数 风湿病患者的炎症反应。1)基因的存在 关节炎易感性与自身免疫性疾病的相关性 正在接受CIA易感性的比较菌株分析的质疑 以及其他关节炎的实验模型。2)确定差异是否 对CIA易感性的差异与其特异性有关 对II型胶原的免疫应答，抗性和抗血清的免疫应答 敏感菌株正在(用酶联免疫吸附试验)进行相对反应性分析。 用分离的大鼠胶原蛋白(II)的螺旋溴化氰(CB)多肽。 3)RT1单倍型菌株为低应答型，对CIA耐药。 将使用RT1内重组子来识别 控制抗胶原免疫反应。检测胶原蛋白的特异性 T抑制细胞，非致关节炎佐剂将在 免疫接种。4)存在特定的“关节炎”区域。 提出了胶原蛋白分子，并将通过两种方法进行测试：a) 以生物化学方法制备单个CB多肽的免疫研究 异种II型胶原蛋白；b)使用杂交瘤技术制备 一组与大鼠胶原(II)反应的单抗将 测试被动将关节炎转移给未接种疫苗的大鼠的能力。 5)组织培养技术正在被用来研究相互作用 滑膜细胞、胶原蛋白和免疫T细胞的研究进展 干扰素和白介素类药物。易感人群之间的遗传差异 以及抵抗力强的大鼠，在这些物质的产生或反应中 免疫调节剂将受到质疑。