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

We identified autoantibodies against TRIM33 in DM plasma, confirming the anti-TIF1 positive profile of our patients. Furthermore, we identified autoantibodies against 11 other TRIM proteins in DM, of which only TRIM21 was identified in healthy controls but with much lower abundance. TRIM21 (Ro52) is a known autoantigen in IIM and related autoimmune disorders, and acts as the highestaffinity Fc receptor in humans. TRIM21 binds cytosolic antibodies bound to non-enveloped viral pathogens, to trigger antibody-dependent intracellular neutralization and proteasomal degradation of the immune complex (Lee, 2017; Rajsbaum et al., 2014) . The autoantibodies we identified against TRIM proteins, other than TRIM33 and TRIM21, have not been observed previously in IIM. TRIM69 inhibits vesicular stomatitis virus transcription and interacts with dengue virus non-structural protein 3 to mediate its poly-ubiquitination and degradation (Kueck et al., 2019; Wang et al., 2018) . TRIMs also regulate antiviral pathways indirectly by mediating innate immunity, influencing the transcription of TI-IFNs, pro-inflammatory cytokines and interferon-stimulated genes (van Tol et al., 2017) .