| Title: | Autoimmunity to synovial extracellular matrix proteins in patients with postinfectious Lyme arthritis |
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| Authors: | ID Kanjana, Korawit (Author)
ID Strle, Klemen (Author)
ID Lochhead, Robert B. (Author)
ID Pianta, Annalisa (Author)
ID Mateyka, Laura M. (Author)
ID Wang, Qi (Author)
ID Arvikar, Sheila (Author)
ID Kling, David E. (Author)
ID Deangelo, Cameron A. (Author)
ID Curham, Lucy (Author), et al. |
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| Files: |  PDF - Presentation file, download (2,04 MB)
MD5: 11B53E586C9CBE4F8F4640D6432629CA
 URL - Source URL, visit https://www.jci.org/articles/view/161170
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| Abstract: | Background. Autoimmune diseases often have strong genetic associations with specific HLA-DR alleles. The synovial lesion in chronic inflammatory forms of arthritis shows marked upregulation of HLA-DR molecules, including in postinfectious Lyme arthritis (LA). However, the identity of HLA-DR–presented peptides, and therefore the reasons for these associations, has frequently remained elusive. Methods. Using immunopeptidomics to detect HLA-DR–presented peptides from synovial tissue, we identified T cell epitopes from 3 extracellular matrix (ECM) proteins in patients with postinfectious LA, identified potential Borreliella burgdorferi–mimic (Bb-mimic) epitopes, and characterized T and B cell responses to these peptides or proteins. Results. Of 24 postinfectious LA patients, 58% had CD4+ T cell responses to at least 1 epitope of 3 ECM proteins, fibronectin-1, laminin B2, and/or collagen Vα1, and 17% of 52 such patients had antibody responses to at least 1 of these proteins. Patients with autoreactive T cell responses had significantly increased frequencies of HLA-DRB1*04 or -DRB1*1501 alleles and more prolonged arthritis. When tetramer reagents were loaded with ECM or corresponding Bb-mimic peptides, binding was only with the autoreactive T cells. A high percentage of ECM-autoreactive CD4+ T cells in synovial fluid were T-bet–expressing Th1 cells, a small percentage were RoRγt-expressing Th17 cells, and a minimal percentage were FoxP3-expressing Tregs. Conclusion. Autoreactive, proinflammatory CD4+ T cells and autoantibodies develop to ECM proteins in a subgroup of postinfectious LA patients who have specific HLA-DR alleles. Rather than the traditional molecular mimicry model, we propose that epitope spreading provides the best explanation for this example of infection-induced autoimmunity. |
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| Keywords: | Lyme arthritis, autoimmune diseases, infectious disease |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2023 |
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| Number of pages: | str. 1-13 |
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| Numbering: | Vol. 133, no. 17, [article no.] e161170 |
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| PID: | 20.500.12556/DiRROS-29656  |
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| UDC: | 616.9 |
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| ISSN on article: | 1558-8238 |
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| DOI: | 10.1172/JCI161170 |
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| COBISS.SI-ID: | 279244035 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 25. 5. 2026;
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| Publication date in DiRROS: | 02.06.2026 |
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| Views: | 64 |
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| Downloads: | 55 |
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