CHRONIC CRYSTAL-INDUCED ARTHRITIS

慢性关节炎是一种多因素事件，涉及免疫性和 非免疫生物系统。这是一个检验假设的试点项目。 1)炎症性疾病“非免疫”成分的遗传变异 关节疾病的存在，以及2)这种遗传变异性有助于 对疾病发病率和严重程度的广泛影响 由患有骨关节炎和其他疾病的老年患者显示 非类风湿关节疾病。现有的动物模型中没有一种 骨性关节炎适用于遗传学评价。 大鼠慢性结晶性关节炎(CCIA)模型的建立 菌株)将通过重复(每周)关节内建立 注射尿酸钠、尿酸钙或焦磷酸钙 水晶。该模式将以临床和临床为基础 急性(单次注射)进展的组织学评价 到慢性(5-8次注射)的关节炎症阶段。实验 变量，如剂量反应，性别和年龄(1-9个月)的测试大鼠 将被评估为重要性。 将对选定的15个近交系大鼠进行CCIA敏感性测试 通过最初确定的最优方案。测试菌株包括 通过美国国立卫生研究院或我们自己的大鼠获得的原型和近交系同源菌株 在犹他大学的殖民地。两种情况下的菌株特异性差异 CCIA的急性期或慢性期将根据严重程度进行选择 或者诱导的简易性。 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) 将与CCIA一起检测Ig G和Ig M抗II型胶原抗体 用ELISA法。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，必须确定为 加重CCIA严重性的组成部分或将其作为压倒一切消除 这些研究中的遗传变异。

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.