The Clinical Study And Biomarker Study Of Idiopathic Inflammatory Myopathy

Objective:This study established the single-centered cohort and multi-centered cohorts of patients with Idiopathic Inflammatory Myopathy(ⅡM).We aimed to investigate the clinical features,risk factors of rare involvement of vital organs,clinical subtypic characterization of IIM.We also aimed to screen for novel cytokines in dermatomyositis(DM).Method:In clinical cohort study,baseline data were retrospectively collected from Peking Union Medical College Hospital(PUMCH)and other connective tissue disease(CTD)centers in China.Cross sectional analysis was performed to describe the baseline clinical characteristics.Case-control study was conducted to identify the risk factors of cardiac involvement,gastrointestinal tract involvement,pneumothorax or pneumomediastinum,malignancy and calcinosis respectively.In study on clinical phenotype,a subgroup analysis based on myositis-specific antibodies(MSAs)was first carried out.Principle component analysis(PCA)based cluster analysis was then performed to identify the clinical subtypes of DM and anti-MDA5 positive DM.The validity of the clustering was confirmed by the significant differences in MSAs and disease activity or damage across the subgroups.In biomarker study,the ProcartaPlexTM Multiplex Immunoassay was used to detect 34 cytokines in DM patients and healthy controls to find potential novel biomarkers for DM.Result:1)Baseline characteristics.A total of 2869 were enrolled in the multi-centered cohorts.71.9%were female.The mean age at disease onset were 46.4±15.4 years.60.3%patients had respiratory involvement,which was the most common organ involved except for skin and muscle.The most common MSA was anti-MDA5 antibody.Glucocorticoids were administrated in 94.1%patients.2)Risk factors.Creatine kinase,y-glutamyl transpeptadase,C-reaction protein and anti-mitochondrial antibody were identified as independent risk factors of cardiac involvement in ⅡM.Male gender,Raynaud phenomenon,skin ulcer,dysphagia and cardiac involvement were identified as independent risk factors of gastrointestinal tract involvement while immunoglobulin G as protective factor.C-reaction protein,interstitial lung disease(ILD)and anti-nuclear antibody(ANA)were independent risk factors of pneumothorax or pneumomediastinum inⅡM.Age,anti-TIF1γ antibody and dysphagia were identified as independent risk factors of malignancy while ILD as protective factor.Vasculitis,Raynaud phenomenon,skin ulcer,respiratory muscle weakness,anti-Mi-2a antibody and anti-NXP2 antibody were independent risk factors of calcinosis while age was protective factor.3)Study on clinical phenotype.The results of subgroup analysis based on myositis-specific antibodies(MSAs)were highly consistent with studies previously reported.Cluster analysis of DM patients identified six distinct clusters.Among them,four clusters were consistent with subgroups previously reported and were validated by MSAs,including tumor-associated DM,DM accompanied by calcinosis,clinically amyopathic DM(CADM)accompanied by ILD and anti synthetase syndrome.Cluster analysis of anti-MDA5 positive DM patients identified four distinct clusters:cluster 1,skin,lung and muscle involvement;cluster 2,heart,lung and muscle involvement;cluster 3,lung and skin involvement;cluster 4,arthritis,skin and muscle involvement.The disease activity and damage were signifigantly different across the four clusters.In biomarker study,fourty DM patients and ten healthy controls were detected using Multiplex Immunoassay.Ten DM associated cytokines,five anti-MDA5 antibody associated cytokines,six ILD associated cytokines,nine erythrocyte sedimentation rate(ESR)associated cytokines,three ferritin associated cytokines and three DAS associated cytokines were identified.Conclusion:This study presented the world largest cohort of ⅡM.Clinical features of ⅡM and risk factors of rare involvement of vital organs in ⅡM were described,providing concrete evidence for early detection and diagnosis of rare involvement of vital organs.The cluster analysis of DM patients and anti-MDA5 antibody positive DM patients identified several distinct subtypes,underscoring the need for better phenotypic characterization to help develop individualized treatments and improve prognosis.Novel cytokines were also identified in DM.This study provided solid evidence for early diagnosis,assessment,clinical subtyping and biomarkers for patients with IIM.