The Clinical Study And Biomarker Study Of Primary Sj(?)gren's Syndrome-associated Lung Involvement

Objective:This study started the single-centered cohort and multi-centered cohort of patients with primary Sjogren's syndrome-associated interstitial lung disease(pSS-ILD).We aimed to investigate the clinical features,risk factors,survival,and prognostic factors of pSS-ILD.We also aimed to screen for novel biomarkers in pSS-ILD and pSS-associated(PAH)by humanMethod:In clinical cohort study,data were retrospectively collected from Peking Union Medical College Hospital and 27 centers connective tissue disease-associated ILD centers in China.Chest high resolution CT(HRCT)and pulmonary function test were performed to confirm and evaluate ILD.Baseline and follow-up data were collected.Cross sectional analysis was conducted to describe the baseline clinical characteristics.pSS patients without lung involvement(pSS-non-ILD)were enrolled as control groups.Case-control study was conducted to identify the risk factors.In prognostic study,the primary end point was all-cause death,and the secondary end point was ILD deterioration.Cumulative probabilities of the endpoints were calculated using the Kaplan-Meier estimator.Cox regression was also conducted to identify the prognostic factors.In biomarker study,the human proteome microarray was used to conduct autoantibody profiling in pSS-ILD and pSS-PAH in order to find potential novel antibody biomarker.Result:A total of 59 patients with pSS-ILD were enrolled in the single-centered cohort,and 258 were enrolled in the multi-centered cohort.1)Baseline characteristics.In single-centered and multi-centered cohorts respectively,94.9%and 88.8%patients were female.The age at baseline were 58.3 + 10.2 and 60.1 + 10.6 years.In 44.1 and 46.5%patients,ILD was the initial manifestation.The most common radiology type was nonspecific interstitial pneumonia(NSIP).Forced vital capacity(FVC)was 86.7 ± 20.2%? 77.3 ± 18.6%in single-centered and multi-centered cohorts.Glucocorticoids were administrated in 76.3%and 65.5%patients.Anti-pulmonary fibrosis pharmaceuticals were used in 5.1%and 3.1%of patients.2)Risk factors.Male gender(OR 2.451,95%CI 1.153-5.059,p = 0.005),age(OR 1.064,95%CI 1.045-1.084,p<0.001),C-reaction protein(OR 1.064,95%CI 1.045-1.084,p<0.001),and anti-Ro52 antibody(OR 2.516,95%CI 1.457-4.343,p<0.001)were identified as independent risk factors of for developing ILD in pSS.3.Survival analysis.A total of 237 patents with complete survival data were enrolled in the survival analysis.Eighteen(7.6%)patients died.The 1-,3-,and 5-year survival rates were 98,1%,93.6%,and 87.6%,respectively.4)Prognostic factors.Male gender(HR 9.076,95%CI 1.514-54.424,p=0.016),age(HR 1.332,95%CI 1.093-1.363,p ?0.001),and carbon monoxide diffusing capacity(DLCO)/predo%?50%(HR 9.007,95%CI 1.446-56.098,p = 0.001)were identified as independent prognostic factors.5)ILD deterioration.A total of 32 patients entered the ILD deterioration analysis.Seven(21.9%)patients deteriorated.The 1-,3-,and 5-year rates of not deteriorating were 88.4%,64.9%and 32.5%.6)Predictive factors for ILD deterioration.Positive for crackles sign(HR 13.322,95%CI 2.395-74.122,p = 0.003).In biomarker study,14 pSS-ILD,14 pSS-PAH,and 12 pSS were screened using human proteome microarray.Eighty-four pSS-ILD associated autoantibodies and 4 pSS-PAH associated autoantibodies were identified.Conclusion:This study presented the world largest cohort of pSS-ILD.Clinical characteristics and risk factors of pSS-ILD in Chinese population were described.Regular screening of ILD by is recommended in high risks patients(male,older age,higher CRP,and positive for anti-Ro52 antibody)for early diagnosis.Survival rates and the prognostic factors were identified.We suggest that patients with prognostic factor for poor clinical outcome should be followed-up closely and start strengthened treatment earlier.Novel autoantibodies were identified in pSS-ILD and pSS-PAH by human proteome microarray.Candidates autoantibodies await further delineation by the disease-focused microarray in a larger cohort.This study provides evidence for early diagnosis,prognosis predicting,and novel biomarkers for patients with pSS-associated lung involvement.