The Clinical Cohort Study Of Systemic Sclerosis And Biomarker Validate Study Of Systemic Sclerosis Associated Interstitial Lung Disease

Objective:In this study,we established a national multi-center clinical cohort of systemic sclerosis to investigate the baseline characteristics,risk factors for organ involvement and therapeutic efficacy.A cohort of SSc-PAH confirmed by right heart catheterization(RHC)was also started,and the baseline characteristics and risk factors was inquired.Furthermore,the biomarkers for diagnosis or evaluation were searched in the SSc and SSc-ILD patients.The study aims to provide evidence for the early diagnosis,risk stratification and personalized treatment selection of SSc patients.Method:This study involves Peking Union Medical College Hospital(PUMCH)and 153 connective tissue disease centers in China.Patients fulfilling the inclusive and exclusive criteria were enrolled,and the baseline and follow-up data were collected.In clinical study,cross-sectional analysis was conducted,describing the baseline characteristics.Case-control study between SSc-SRC or SSc-LVDd patients and SSc patients without organ-involvement from EUSTAR database was conducted to identify risk factors.SSc-PAH patients diagnosed by right heart catheterization(RHC)were enrolled,and the baseline characteristics were analyzed through cross-sectional analysis.Case-control analysis was carried out between SSc-PAH and SSc non-PAH patients to inquire independent risk factors.According to the application of immunosuppressive agents in patients’ baseline treatment,patients without immunosuppressive agents,with MTX alone and CTX alone were selected for short-term efficacy evaluation,in which the pulmonary function before and after 12-month treatment were compared to evaluate the therapy efficacy.In basic research,the serum levels of anti-GAD1 antibody,anti-RPLPO antibody and anti-MLYCD antibody in healthy control,SSc-nonILD and SSc-ILD patients were detected by ELISA.Further study of the correlation between the auto-antibodies and the diagnosis and disease severity was verified.Results:A total of 2809 patients with SSc were enrolled in this multicenter cohort.Results of SSc cohort study:1.Baseline characteristics.84.6%of the multi-center SSc patients were female,and the baseline age was 46.6+13.2 years old.Interstitial lung disease was the most common manifestation of SSc-related organ involvement,accounting for 54.7%.Rodnan skin score was 6(0,48),and baseline glucocorticoid usage rate was 82.2%.2.Risk factors.The independent risk factor for LVDd in SSc patients was the Rodnan skin score(OR 1.053,95%Cl 1.015-1.092),and the independent protective factors was onset age(OR 0.952,95%CI 0.929-0.975,P<0.001).DcSSc(OR 3.872,95%CI 1.169-12.822,P=0.027),arthritis(OR 3.522,95%CI 1.088-11.403,P=0.036),pulmonary hypertension(OR 7.005,95%Cl 2.323-21.121,P=0.001),and thrombocytopenia(OR 1.452,95%CI 1.269-7.849,P=0.002)were independent risk factors for SSc-SRC patients.3.Treatment efficacy analysis.There was no significant deterioration of lung function in SSc patients without baseline immunosuppressive therapy after 12-month follow-up.In patients using MTX as the only immunosuppressive agent,the DLCO and DLCO/predicted value deteriorated significantly,while in SSc-ILD patients treated with CTX as the only immunosuppressive therapy,TLC and TLC/Pred were significantly improved.SSc-PAH cohort study:1.Baseline characteristics.90.4%of multi-center SSc-PAH patients were female and their baseline age was 50.2+14.5.RHC early diagnostic rate was 40.9%.The mean pulmonary artery pressure was 39.4+12.9 mmHg.83.1%of patients were treated with glucocorticoid,while 73.5%of patients were treated with immunosuppressive agents.40.9%of patients were treated with PAH vasodilators.2.Risk factors.Anti-RNP antibody(OR 5.925,95%CI 1.120-31.355)and high IgG level(OR 1.811,95%CI 1.686-1.958)were independent risk factors for PAH in SSc patients.Normalized DLCO/predicted value(OR 0.947,95%CI 0.911-0.985)was an independent protective factor for SSc-PAH.Results of biomarker study:The serum expression level of anti-RPLPO antibody of SSc patients was significantly higher than that of healthy people.The diagnostic specificity was high when the cut-off value was serum concentration>4.381 μg/ml.The proportion of digital ulcer was significantly higher in patients with higher anti-RPLPO antibody titer,indicating a potential correlation with microvascuopathy.Conclusion:The largest SSc cohort in China was established in our study.Baseline characteristics and risk factors of organ involvement were obtained and regular screening is recommended in high-risk patients.Therapy evaluation of immunosuppressive agents is still not fully understood.Anti-RPLPO antibody was identified in our study as a potential diagnostic and evaluating biomarker.This study provides a theoretical basis for early diagnosis,disease assessment,risk stratification,individualized treatment and biomarker development of SSc patients.