OP0181 MOLECULAR CHARACTERIZATION AND STRATIFICATION OF IDIOPATHIC INFLAMMATORY MYOPATHIES: ON THE BASIS OF SKELETAL MUSCLE TRANSCRIPTOME STUDY

Abstract

Background: Idiopathic inflammatory myopathies (IIM) are a group of complicated heterogenous autoimmune diseases, to date, little is known about its skeletal muscle transcriptomic features. Objectives: Here, we performed skeletal muscle RNA-sequencing (RNA-seq) to discover the global muscle transcriptional signature of IIM based on myositis-specific antibodies (MSA) profiles and investigate the potential molecular pathway of IIM. Methods: Muscle specimen were taken from 60 patients with IIM, 6 patients with non-IIM myopathies and 9 healthy controls. The serum and PBMC samples were also obtained from the IIM patients at the time of muscle biopsy. For RNA-seq, IIM was dissected into eight groups based on their MSA profiles: MSA and ANA negative (n = 4), anti-synthetase antibodies positive (n= 13), -MDA5 positive (n = 6), -NXP-2 positive (n = 7), -TIF-1γ positive (n = 10), -SRP or anti-HMGCR positive (n = 6), -Mi-2 positive (n = 7), MSA negative but anti-Ro-52 positive (n = 7). RNA from muscle specimen were extracted according to manufactory guide and sequenced using Illumina HiSeq2500. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed on sequencing cohorts and expanding cohorts to validate the results of RNA-seq. Immunohistochemistry was also performed on muscle biopsy to determine the MxA expression in different MSA subgroups. Results: To define the global muscle signature of IIM, all IIM samples were compared to NC and total of 1637 transcripts were differentially expressed (log2 Fold Change > 1, Padj Conclusion: We revealed a prominent IFN signature and MSA-based ISG expression heterogeneity in IIM through muscle transcriptomics. Preliminary results showed that the IFN muscle signature may play a predominant role in some subgroups but not all IIM groups in the pathogenesis of IIM.