Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis.
- Resource Type
- Academic Journal
- Authors
- Megremis S; Division of Evolution and Genomic Sciences, University of Manchester, Manchester, UK.; Walker TDJ; Division of Cancer Sciences, University of Manchester, Manchester, UK.; He X; Division of Cancer Sciences, University of Manchester, Manchester, UK.; O'Sullivan J; Division of Evolution and Genomic Sciences, University of Manchester, Manchester, UK.; Ollier WER; Division of Population Health, Health Services Research & Primary Care, University of Manchester, Manchester, UK.; Centre for Bioscience, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.; Chinoy H; National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, University of Manchester, Manchester, UK.; Department of Rheumatology, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Salford, UK.; Pendleton N; Division of Neuroscience & Experimental Psychology, University of Manchester, Manchester, UK.; Payton A; Division of Informatics, Imaging & Data Sciences, University of Manchester, Manchester, UK.; Hampson L; Division of Cancer Sciences, University of Manchester, Manchester, UK.; Hampson I; Division of Cancer Sciences, University of Manchester, Manchester, UK.; Lamb JA; Division of Population Health, Health Services Research & Primary Care, University of Manchester, Manchester, UK. Janine.Lamb@manchester.ac.uk.
- Source
- Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE
- Subject
- Language
- English
We investigate the accumulated microbial and autoantigen antibody repertoire in adult-onset dermatomyositis patients sero-positive for TIF1γ (TRIM33) autoantibodies. We use an untargeted high-throughput approach which combines immunoglobulin disease-specific epitope-enrichment and identification of microbial and human antigens. We observe antibodies recognizing a wider repertoire of microbial antigens in dermatomyositis. Antibodies recognizing viruses and Poxviridae family species are significantly enriched. The identified autoantibodies recognise a large portion of the human proteome, including interferon regulated proteins; these proteins cluster in specific biological processes. In addition to TRIM33, we identify autoantibodies against eleven further TRIM proteins, including TRIM21. Some of these TRIM proteins share epitope homology with specific viral species including poxviruses. Our data suggest antibody accumulation in dermatomyositis against an expanded diversity of microbial and human proteins and evidence of non-random targeting of specific signalling pathways. Our findings indicate that molecular mimicry and epitope spreading events may play a role in dermatomyositis pathogenesis.