Therapeutic Efficacy And Mechanism Study Of Iguratimod On Sjogren’s Syndrome

Background: Sjogren’s syndrome (SS) is a systemic disorder characterizedby lymphocyte infiltration in exocrine gland, particularly of salivaryglandsand lacrimal glands, leading to dry mouth and dry eye.SS often occurs inyoung women. At present，SS has become the highest incidence of connectivetissue diseases now.System function damage as cause of extra-glandinvolvement of organs is a major complication of the disease and the cause ofdeath.The current study showed that B lymphocytes play an important role in thepathogenesis of SS. Activation and apoptotic clearance dysfunction ofB lymphocytes cause immunoglobulin complex production inserum.Iguratimod, as a novel disease modifying anti-rheumatic drug, inhibits Blymphocytes、 the production of immunoglobulins and various B-cellinflammatory cytokines(interleukin-1,interleukin-6，interleukin-8and TNF-α)to ease disease.Thus, we propose the hypothesis that Iguratimod just canimprove Sjogren’s syndrome through inhibiting B lymphocyte.Bjective:To evaluate the clinical efficacy and explore the mechanism ofIguratimod in the treatment of primary Sjogren’s syndrome.Methods:50patients met Inclusion and exclusion criteria wererandomly assigned into2groups:patients in the experimental group （Iguratimod） are treated with Iguratimod combined with conventionaldrug therapy， meanwhile patients in the control group are treatedwith conventional therapy. The conventional therapy consists of low doses ofprednisone, hydroxychloroquine, aspirin and supporting medications. Patientswill be tested every four weeks and parameters consists of serologic test (PLT,IgG), Schirmer I test and ESSPRI score, ESSDAI score.While each group willbe randomly selected10subjects,they will be test B cell surfacemolecules(CD20, BAFF-R、PLT-3、CD38、IgD) in the serum by flow cytometry.Results：1. All clinical efficacy parameters of observation improved significantly inIguratimod’group(P<0.05). Platelets（PLT）and Schirmer I test in control grouphave no significantly difference（P>0.05）.The acting time and efficacyin Iguratimod’s group are significantly higher than that in controlgroup(P<0.05).2. The adverse reaction events in two groups do not show significantlydifference (P>0.05).3. After intervention,BAFF-R and CD38、IgD(double positive) expression inIguratimod and control group have significant difference (P<0.05),andexpression change in Iguratimod group have significant difference compared tocontrol group.(P<0.05).Conclusion1.In the treatment of Sjogren syndrome,Iguratimod combined with conventionaltherapy is superior over conventional therapy in terms of acting time and efficacy.2.Iguratimod does not increase the risk of adverse events.3.The mechanism of Iguratimod in SS is probably inhibiting BAFF-R positiveB lymphocyte and Bm2cell to inhibit the function of B cell secretion and acton ectopic germinal center(GC) and peripheral blood for Reducing gland B cellpathological invasion,not by inhibiting the FLT-3positive B-cell and targetedfor CD20B-cells.