Therapeutic Effects And Mechanisms Of Iguratimod On Primary Sj?gren's Syndrome

Objective To investigate the therapeutic effect and the mechanism of primary Sjogren's syndrome(pSS)with iguratimod treatment.Methods A total of 30 patients with primary Sj?gren's syndrome were enrolled in a single-center,open,and self-controlled study for 16 weeks.Percentage of CD19~+CD27~+memory B cells in peripheralblood was analyzed by flow cytometry.Observing the clinical symptoms and signs,laboratory indexes,the European league against rheumatism(EULAR),Sj?gren's syndrome disease activity index(ESSDAI)score,and EULAR Sj?gren's syndrome patient reported index(ESSPRI)score.Moreover,thirty-six 7-week-old NOD mice were randomly divided into 3 groups of 12 mice each,empty vector solution group,10 mg/kgiguratimod group,and 20 mg/kg iguratimod group respectively,After 1 week of adaptation,the mice were treated with different doses of iguratide by intragastric administration per day for 8 weeks.Then the percentage of spleen CD19~+CD27~+memory B cells were tested by flow cytometry.Results(1)After the treatment of Iguratimod for 16 weeks,the ESSDAI score and ESSPRI score were reduced in pSS patients.The percentage of CD19~+CD27~+memory B cells in peripheral blood,the serum levels of IgG,IgA,IgM,erythrocyte sedimentation rate(ESR)and rheumatoid factor(RF)were lower than before treatment,the difference was statistically significant(21.67±6.14 vs 17.92±5.85,P=0.019;3.26±1.56 vs 2.51±1.04,P=0.032;1.73±0.75 vs 1.34±0.56,P=0.026;44.63±26.04 vs 29.93±21.79,P=0.021;73.26±13.38vs 39.21±7.16,P=0.013;0.235±0.133 vs 0.163±0.085,P=0.041).(2)There were 5 cases of side effects,including 2 cases of gastrointestinal discomfort,2cases of mild hepatic dysfunction,and 1 case of generalized body rash,Nevertheless,there were no serious adverse reactions,such as peptic ulcer?granulocyte deficiency?and infection.(3)Animal experiment results showed,after 8 weeks of intragastric administration,that the proportion of spleen CD19~+CD27~+memory B cells in 10 mg/kg iguratide group and20 mg/kg iguratide group was significantly lower than that in of empty vector group(0.406±0.153 vs 0.627±0.127,P<0.001;0.431±0.127vs0.627±0.127,P<0.001).Conclusion These findings indicated that Iguratimod could alleviate the conditions of patients with pSS,reduce the level of immunoglobulin,regulate the B cell development,and have good tolerability and high safety.