Next generation sequencing of RNA from muscle biopsies shows marked differences between inflammatory myositis, inclusion body myositis, and controls

Abstract Inflammatory myositis (IM) is a multi-system inflammatory disorder characterised by a variable triad of muscular weakness, interstitial lung disease, and cutaneous manifestations. A serological profile is now recognised in over 80% of cases and correlates closely with the phenotypic manifestation of the disease. The largest serological subgroup of IM is anti-Jo-1 (an anti-tRNA synthetase antibody). Present standard treatment is with systemic immunosuppression. Inclusion body myositis (IBM) differs from IM by affecting peripheral and proximal muscles and tends to have little in the way of multi-organ involvement. IBM tends to respond poorly to immunosuppression, and currently does not have an as well recognised serological profile as IM. Recent research suggests that non-coding RNA plays a crucial role in orchestrating protein transcription, and aberrant non-coding RNA expression may play a key part in IM and IBM. Advances in sequencing techniques now enable detailed analysis of RNA transcription and may help unravel the pathogenesis of IM and IBM. In this pilot study we investigate the differences in expression of coding and non-coding RNA in IM (anti- Jo-1 antibody positive) and IBM. RNA was extracted from each muscle biopsy and pooled into three samples (IM, IBM, and control) for sequencing. RNA was extracted from five muscle biopsy samples for each of the IM and control group, and two for the IBM group. The muscle transcriptome was determined with next generation sequencing (Illumina Hi-Seq 2000, Poly A+ extraction). Data were mapped onto the human genome and changes in expression were analysed. Preliminary data have shown significant differential changes in transcription of cell structure and inflammatory response proteins, as well as marked variation in skeletal-muscle-specific long non-coding RNAs, between the three groups. Funding National Institute for Health Research.