Decreased Levels Of Serum IL-35 In Patients With Mixed Connective Tissue Disease

Objective: Mixed connective tissue disease(MCTD)is an autoimmune disease characterized by the high-titer antinuclear antibody(ANA)and anti-U1RNP(n RNP)antibody in the serum,Raynaud’s phenomenon,swelling of the hands,and multiple joint pain,arthritis,myositis,esophageal motor dysfunction,pulmonary arterial hypertension and other clinical syndromes.Cardiovascular system,respiratory system,urinary system,digestive system,nervous system and blood system can be involved.Interleukin(IL)-35 is an immunosuppressive cytokine secreted by regulatory T cells(Treg),which can play an immunomodulatory role in the body.Studies have found that IL-35 can participate in a variety of autoimmune diseases such as rheumatoid arthritis(RA),Sjogren’s Syndrome(p SS),and systemic lupus erythematosus(SLE).But there are no related reports in the MCTD patients.The purpose of this study was to explore the relationship between the level of IL-35 and clinical indicators,disease activity and clinical characteristics in MCTD patients.Method: 57 MCTD patients were enrolled in the Department of Rheumatology an Immunology,and of the First Affiliated Hospital of China Medical University from July 2019 to November 2019.20 healthy volunteers from the physical examination center were recruited as the control group(HCs).5ml venous blood was collected from each subject.The level of IL-35 in the serum was detected by enzyme-linked immunosorbent assay(ELISA).Laboratory indexes,including C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),rheumatoid factor(RF),blood cell count,creatine kinase(CK),lactate dehydrogenase(LDH),anti-U1 RNP antibody,anti-SSA antibody,anti-SSB antibody,anti-SM antibody,Ro-52 antibody,proteinuria,were collected.Pulmonary arterial hypertension(PAH)was evaluated by color Doppler ultrasonography.Determination of interstitial lung disease(ILD)was confirmed by high-resolution computed tomography(HRCT).Results: The serum IL-35 level of MCTD patients was significantly reduced compared with the control group(±SD,ng/m L: 0.613±0.118 vs 0.722±0.122,P=0.001).In addition,IL-35 levels were positively correlated with RF levels(r=0.426,P=0.001),but Xno correlation were found with CK,LDH,CRP,and ESR(P=0.514,P=0.499,P=0.855,P=0.482,respectively).In clinical features,patients with Raynaud phenomenon,sclerodactyly and ILD have higher levels of IL-35(±SD,ng/m L: 0.641±0.113 vs 0.557±0.110,P=0.009;0.650± 0.123 vs 0.576±0.102,P=0.017;0.653±0.125 vs 0.553±0.076,P=0.001,respectively).However,levels of IL-35 in MCTD patients with PAH,proteinuria,anti-SSA antibody-positive,anti-SSB antibody-positive,SM antibody-positive,Ro-52 antibody-positive showed no significant difference compared with those without(P=0.180,P=0.700,P=0.827,P=0.450,P=0.523,P=0.683,respectively).Conclusion: The level of IL-35 in patients with MCTD is lower than that in healthy controls,suggesting that IL-35 can participate in the pathogenesis of MCTD,and has a certain relationship with disease activity and clinical characteristics,which provides supporting evidence for the treatment of MCTD.