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

To describe the biological functions of all the identified proteins the Gene Ontology (GO) framework was used ( Figure 5B & 5C). In DM P20 eight GO biological processes were highly enriched ( Figure 5B ). These processes were represented by an average of 25.6% of GO-specific proteins (n=996, 95%CI: 21.2%-29.7%) ( Figure S6A ). In HC P20, ten GO processes were enriched with an overall lower average coverage of 14.5% (n=592, range: 12.5%-15.7%), as less proteins mapped to the same GO unit. In the top-ranked GO processes enriched in DM, the GO coverage was higher in DM than HC regardless of the GO process ( Figure S6A ). More than one third (39.2%: 996 out of 2537) of the DM autoantibody targets were part of the 8 identified biological processes; 18.6% of them (186 out of 996) were also present in HC P20. DM processes involved structural elements including microtubulebased processes, actin-filament functions, cell junction organisation, extracellular structure organisation, cell morphogenesis in differentiation and small GTPase mediated signal transduction ( Figure 5B ). PTK2 and ROCK2 were shared between 7 out of 8 functions, and, KIF14, NDEL1, SRGAP2, APP, PRKCZ, and CLASP2 were shared amongst 6 out of 8 functions ( Figure 5D ). None of these proteins were observed in HC. The fact that the identified DM-specific and HC-specific . 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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 proteins were robustly clustered in biological functions suggests non-random targeting of specific signalling pathways by autoantibodies. In DM, these processes share multiple autoantibody protein targets suggesting the presence of a DM-specific autoantibody-targeted proteome module ( Figure S6B ).