HLA-DRβ1特异性非T细胞结合肽对胶原性关节炎的抑制作用

被引：13

作者：

周强

程永静

张学武

吕厚山

栗占国

机构：

[1] 北京大学人民医院风湿免疫科

来源：

中华风湿病学杂志 | 2002年 / 06期

关键词：

HLA-DR抗原; 关节炎,佐剂性; 关节炎,类风湿;

D O I：

暂无

中图分类号：

R593.22 [类风湿性关节炎];

学科分类号：

摘要：

目的　研究HLA DRβ1特异性非T细胞结合肽对胶原性关节炎的抑制作用 ,探索类风湿关节炎新的免疫治疗方法。方法　以丙氨酸及甘氨酸替换Ⅱ型胶原 (CⅡ ) 2 6 3 2 72多肽中与T细胞受体结合的氨基酸 ,利用HLA DR1转基因抗原呈递细胞及CⅡ特异性T细胞组成的激活体系 ,从这些CⅡ 2 6 3 2 72修饰肽中筛选非T细胞结合肽。牛CⅡ +完全福氏佐剂诱导大鼠胶原性关节炎 (CIA)动物模型 ,应用不同剂量 (10、5 0、10 0 μg)的非T细胞结合肽 2 6 8A皮下注射进行为期 16d的治疗 ,观察大鼠关节肿胀的变化情况。酶联免疫吸附法 (ELISA)检测外周血CⅡ抗体和肿瘤坏死因了 (TNF) α浓度 ,HE染色检测CIA病理变化。结果　 7条CⅡ 2 6 3 2 72修饰肽中以丙氨酸替换第 2 6 7、2 6 8、2 6 9、2 70位残基的 4条肽 (2 6 7A、2 6 8A、2 6 9A及 2 70A)和用丙氨酸和甘氨酸连续替换 2 6 8、2 6 9、2 70位残基的 1条肽 (Sub2 6 8 2 70 )对T细胞激活能力显著低于原型肽 (P <0 0 1)。利用 2 6 8A多肽对CIA进行治疗的结果发现 ,3个治疗组CIA缓解率显著高于对照组 (P <0 0 5或P <0 0 1) ;3个治疗组的关节炎评分显著低于对照组 (P <0 0 5或P <0 0 1)。 3个治疗组TNF α浓度及CⅡ抗体浓度均显著低于对照组 (P <0 0 5或P <0 0 1)。结论　HL

引用

页码：397 / 401

页数：5

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