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

Due to the role of TRIM proteins in IFN signalling, we asked whether the autoantibody protein-targets are regulated by interferons. In the DM dataset 1,560 proteins were predicted to be regulated by IFNs compared to 518 in HC (Interferome v2.01) (Rusinova et al., 2013) . The vast majority of these proteins are regulated by interferons type I, type II or both ( Figure S5A ). Regardless of the IFN type we observed a higher number of IFN-regulated proteins in DM compared to HC suggesting a DM-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 It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the .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 enrichment of immunoglobulins against IFN-regulated human proteins. We focused our search directly for IFN autoantibodies expressed in our samples. In DM, IFNGR1 autoantibodies were present, whereas they were absent in HC ( Figure S5B ). We expanded our search for autoantibodies against known proteins that are highly ranked within the IFNG signalling pathway (gene rank within the SuperPath; GeneCardsSuite: PathCards) (Belinky et al., 2015) . Autoantibodies against 26 IFNGrelated proteins were observed in DM, whereas only 5 were found in HC ( Figure S5B ). The proteinprotein interaction (PPI) enrichment score in DM was <1.0e-16 versus 0.123 in the healthy sample (STRING 11.0)(Szklarczyk et al., 2019) ( Figure S5C & 5D). Overall, these data suggest the accumulation of antibodies in DM against proteins that strongly contribute to IFNG signalling and the broader antiviral mechanism by IFN-regulated proteins.