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

The finding of antibodies against a human protein does not mean that this was the antigen against which the antibody was raised, as pathogen-derived proteins can mimic endogenous epitopes (Panoutsakopoulou et al., 2001; Walker and Jeffrey, 1986) . This might explain inconsistencies between the universal cellular distribution of specific antigens and the specific skeletal muscle target . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 of the disease (Walker and Jeffrey, 1986) . In support of this, we observed that certain DM-specific TRIM epitopes are shared amongst different viruses. TRIM epitopes did not form a separate phylogenetic cluster but were dispersed throughout the viral epitope phylogenetic tree, suggesting that accumulated antibodies against TRIM proteins might be the product of a primal molecular mimicry event and subsequent epitope spreading rather than increased TRIM protein production. This is supported by the observation that the gene expression levels of autoantigens in myositis muscle biopsies do not correlate with the levels of circulating autoantibodies recognizing each cognate endogenous autoantigen; instead they are directly associated with the expression of muscle regeneration markers (Pinal-Fernandez et al., 2019) .