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

Notably, the TRIM protein family expanded very rapidly in evolution, coinciding with development of the adaptive immune system, suggesting that TRIMs may have evolved to fine-tune interactions between the increasingly complex innate and adaptive immune systems Versteeg et al., 2014) . Deregulated activity of approximately one third of the TRIM proteins has been associated with the development of various type of human cancer (Vunjak and Versteeg, 2019) . For example, TRIM47 and TRIM27 have an oncogenic role in colorectal, prostate, oesophageal, ovarian . CC-BY-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.25.007534 doi: bioRxiv preprint and non-small cell lung cancer, promoting proliferation and metastasis (Han et al., 2017; Liang et al., 2019; Zhang et al., 2018) . Conversely TRIM3 has tumour suppressor activity, inhibiting the growth of liver, colorectal and gastric cancer (Boulay et al., 2009) . The presence of autoantibodies against cancerassociated TRIMs accords with the strong temporal association between myositis and the development of malignancies in adult-onset anti-TIF1γ positive DM (Oldroyd et al., 2019) , consistent with the high proportion of cancer-associated myositis cases in the current study (45%). Overall, the expanded targeting of TRIM proteins we observed in DM plasma supports the role of the TRIM RING-type E3 ubiquitin ligase subfamily as powerful regulators of the immune system through post-translational modification (Hage and Rajsbaum, 2019; van Tol et al., 2017) .