摘要:
目的 探讨艾拉莫德治疗原发性干燥综合征（primary Sjögren's syndrome，pSS）的有效性和安全性。方法 对30例pSS患者进行单中心、开放、自身对照的16周临床研究。采用流式细胞术检测患者外周血CD19+CD27+记忆性B细胞的百分率，观察患者的临床症状和体征、实验室指标、欧洲抗风湿病联盟干燥综合征疾病活动指数（the European league against rheumatism Sjögren's syndrome disease activity index，ESSDAI）评分及欧洲抗风湿病联盟干燥综合征患者报告指数（the European league against rheumatism Sjögren's syndrome patient reported index，ESSPRI）评分。同时将36只7周龄非肥胖型糖尿病（non-obese diabetic，NOD）小鼠随机分为空载体溶液组、10 mg/kg艾拉莫德组、20 mg/kg艾拉莫德组，每组12只，适应1周后分剂量灌胃处理，每日1次连续灌胃8周，流式细胞术检测小鼠脾脏中CD19+CD27+记忆B细胞比例。结果 经艾拉莫德治疗16周后，患者ESSDAI评分及ESSPRI评分均有所改善，免疫球蛋白（IgG、IgA、IgM）、血沉、类风湿因子及外周血CD19+CD27+记忆性B细胞的百分率均较治疗前降低（均有P<0.05）。治疗过程中出现胃肠道不良反应、轻度肝功能异常各2例，全身皮疹1例，未出现与药物相关的严重不良反应。动物实验证实艾拉莫德灌胃8周后10 mg/kg艾拉莫德组、20 mg/kg艾拉莫德组小鼠脾脏中CD19+CD27+记忆B细胞所占比例与空载体组相比降低（均有P<0.05）。结论 艾拉莫德可改善pSS患者病情，降低免疫球蛋白水平、调节B细胞亚群、耐受性好、安全性高。
Abstract:
Objective To explore the effectiveness and safety of Iguratimod on the patients with primary Sjögren's syndrome (pSS). Methods A total of 30 patients with primary Sjögren's syndrome were enrolled in a single-center,open,and self-controlled study for 16 weeks. Percentage of CD19+CD27+ memory B cells in peripheral blood was analyzed by flow cytometry. The clinical symptoms and signs of patients with laboratory indexes were observed, the European league against rheumatism(EULAR) Sjögren's syndrome disease activity index (ESSDAI)score and EULAR Sjögren's syndrome patient reported index (ESSPRI) score were evaluated. At the same time, 36 7-week-old nod mice were randomly divided into empty vector solution group, 10 mg/kg iguratide group, 20 mg/kg iguratide group respectively, 12 rats in each group. After 1 week of adaptation, the rats were treated with different doses of intragastric administration per day for 8 weeks. The percentage of CD19+CD27+ memory B cells in the spleen of mouse was detected by flow cytometry. Results After the treatment of Iguratimod for 16 weeks,the ESSDAI score and ESSPRI score were improved in pSS patients. The percentage of CD19+CD27+ memory B cells in peripheral blood,the level of IgG,IgA,IgM in serum,erythrocyte sedimentation rate (ESR)and rheumatoid factor (RF)were reduced respectively (all P<0.05). There were 5 cases of side effects,including 2 cases of gastrointestinal discomfort, 2 cases of mild hepatic dysfunction, and 1 case of generalized body rash, nevertheless, there were no serious adverse reactions, such as peptic ulcer, granulocyte deficiency, infection, etc. Meanwhile, the animal experiment further confirmed that the proportion of CD19+CD27+ memory B cells in the spleen of mice after 8 weeks of intragastric administration in 10 mg/kg iguratide group and 20 mg/kg iguratide group was significantly lower than that of empty vector group (all P<0.05). Conclusion These findings indicate that Iguratimod could improve the condition of patients with pSS, reduce the level of immunoglobulin, regulate the B cell subsets, and have good tolerability and high safety.
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