Microbial and autoantibody immunogenic repertoires in TIF1? autoantibody positive dermatomyositis

Spyridon Megremis; Thomas Walker; Xiaotong He; James O'Sullivan; William E.R. Ollier; Hector Chinoy; Neil Pendleton; Antony Payton; Lynne Hampson; Ian Hampson; Janine Lamb

Autoantibodies are a key feature of IIM, in common with other autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Myositis-specific autoantibodies, present in approximately 60%-70% of individuals with IIM, are directed against a range of cytoplasmic or nuclear components involved in key intracellular processes, including protein synthesis and chromatin re-modelling . These myositis-specific autoantibodies are often associated with particular clinical features. Individuals with autoantibodies targeting the cytoplasmic nucleic acid sensor MDA5 (also called interferon induced with helicase C domain 1, IFIH1) can present with rapidly progressive interstitial lung disease which is associated with high mortality (Abe et al., 2017; Betteridge et al., 2019) . Several members of the tripartite motif (TRIM) protein family are known autoantibody targets in IIM, and there is a strong temporal association between adult-onset dermatomyositis and malignancy onset in individuals with antibodies to transcription intermediary factor 1γ (TIF1γ, TRIM33) (Oldroyd et al., 2019) . Many TRIM proteins are important immune regulators (van Tol et al., 2017; Versteeg et al., 2014) , and dysregulation of TRIM proteins leading to reduced ability to restrict viral infection has been reported in several autoimmune diseases, including systemic lupus erythematosus and inflammatory bowel disease (Oke et al., 2009; Zhou et al., 2018) .