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Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis

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...

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Autores principales: Megremis, Spyridon, Walker, Thomas D. J., He, Xiaotong, O’Sullivan, James, Ollier, William E. R., Chinoy, Hector, Pendleton, Neil, Payton, Antony, Hampson, Lynne, Hampson, Ian, Lamb, Janine A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997983/
https://www.ncbi.nlm.nih.gov/pubmed/33772100
http://dx.doi.org/10.1038/s42003-021-01932-6
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author Megremis, Spyridon
Walker, Thomas D. J.
He, Xiaotong
O’Sullivan, James
Ollier, William E. R.
Chinoy, Hector
Pendleton, Neil
Payton, Antony
Hampson, Lynne
Hampson, Ian
Lamb, Janine A.
author_facet Megremis, Spyridon
Walker, Thomas D. J.
He, Xiaotong
O’Sullivan, James
Ollier, William E. R.
Chinoy, Hector
Pendleton, Neil
Payton, Antony
Hampson, Lynne
Hampson, Ian
Lamb, Janine A.
author_sort Megremis, Spyridon
collection PubMed
description 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.
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spelling pubmed-79979832021-04-16 Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis Megremis, Spyridon Walker, Thomas D. J. He, Xiaotong O’Sullivan, James Ollier, William E. R. Chinoy, Hector Pendleton, Neil Payton, Antony Hampson, Lynne Hampson, Ian Lamb, Janine A. Commun Biol Article 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. Nature Publishing Group UK 2021-03-26 /pmc/articles/PMC7997983/ /pubmed/33772100 http://dx.doi.org/10.1038/s42003-021-01932-6 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Megremis, Spyridon
Walker, Thomas D. J.
He, Xiaotong
O’Sullivan, James
Ollier, William E. R.
Chinoy, Hector
Pendleton, Neil
Payton, Antony
Hampson, Lynne
Hampson, Ian
Lamb, Janine A.
Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis
title Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis
title_full Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis
title_fullStr Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis
title_full_unstemmed Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis
title_short Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis
title_sort analysis of human total antibody repertoires in tif1γ autoantibody positive dermatomyositis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997983/
https://www.ncbi.nlm.nih.gov/pubmed/33772100
http://dx.doi.org/10.1038/s42003-021-01932-6
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