CHRONIC CRYSTAL-INDUCED ARTHRITIS

慢性晶体引起的关节炎

• 批准号: 3422483
• 负责人: Marie M. Griffiths
• 金额: $ 2.17万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-02-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3422483
• 关键词: arthritis; autoantibody; calcium; chronic disease /disorder; crystallization; disease /disorder model; enzyme linked immunosorbent assay; genetic strain; immunogenetics; immunoglobulin G; immunoglobulin M; model design /development; pyrophosphates; sodium

Chronic arthritis is a multifactorial event that involves both immune and nonimmune biologic systems. This is a pilot project to test the hypotheses that 1) genetic variation in the "non-immune" components of inflammatory joint disease exist, and 2) that this inherited variability contributes significantly to the wide spectrum of disease incidence and severity that is displayed by elderly patients with osteoarthritis and other non-rheumatoid joint diseases. None of the existing animal models of osteoarthritis are suitable for genetic evaluation. A model of chronic crystal-induced arthritis (CCIA) in rats (LEW, DA strains) will be established by repeated (weekly) intra-articular injections of sodium urate, calcium urate, or calcium pyrophosphate crystals. The model will be characterized on the basis of clinical and histological evaluations of progression from the acute (single injection) to the chronic (5-8 injections) stages of joint inflammation. Experimental variables such as dose-response, sex and age (1-9 months) of the test rats will be assessed for importance. Selected (15) inbred rat strains will be tested for susceptibility to CCIA by the optimum protocol as determined initially. Test strains include prototype and inbred-congenic strains available through NIH or our own rat colony at the University of Utah. Strain-specific differences in either the acute or chronic phases of CCIA will be sought on the basis of severity or ease of induction. To determine if auto-antibody to cartilage collagen develops secondary to chronic arthritis, serum and joint eluates (dilute acetic acid) from rats with CCIA will be assayed for IgG and IgM anti-type II collagen antibodies by ELISA. This is important, as genetic variation in degree of immune response to collagen is known and must be either identified as an aggravating component of CCIA severity or eliminated as an overriding genetic variant in these studies.

慢性关节炎是一个多因素的事件，涉及免疫和 非免疫生物系统。 这是一个试验性项目， 1）炎症性疾病的“非免疫”成分中的遗传变异， 关节疾病存在，2）这种遗传变异有助于 对广泛的疾病发病率和严重程度有显著影响， 老年骨关节炎患者和其他 非类风湿性关节疾病。 现有的动物模型中， 骨关节炎适合于遗传评估。 建立大鼠慢性晶体诱导性关节炎（CCIA）模型（LEW，DA 将通过重复（每周）关节内 注射尿酸钠、尿酸钙或焦磷酸钙 晶体 该模型将根据临床和 从急性（单次注射）进展的组织学评价 慢性（5-8次注射）关节炎症阶段。 实验 试验大鼠的剂量反应、性别和年龄（1-9个月）等变量 将被评估其重要性。 将检测选定的（15）近交系大鼠品系对CCIA的敏感性 通过最初确定的最佳方案。 测试菌株包括 通过NIH或我们自己的大鼠获得的原型和近交系同源菌株 在犹他州大学的殖民地。 菌株特异性差异 CCIA的急性期或慢性期将根据严重程度来确定 或易于归纳。 为了确定软骨胶原自身抗体是否继发于 慢性关节炎，大鼠血清和关节洗脱液（稀醋酸） 用CCIA测定IgG和IgM抗II型胶原抗体 采用ELISA 这一点很重要，因为免疫程度的遗传变异 对胶原蛋白的反应是已知的，并且必须被鉴定为 CCIA严重程度的加重成分或作为压倒性因素删除 这些研究中的遗传变异。