20.500.12556/DiRROS-29656 Autoimmunity to synovial extracellular matrix proteins in patients with postinfectious Lyme arthritis 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. Lyme arthritis autoimmune diseases infectious disease true false true Angleški jezik Ni določen Neznano 2026-06-02 13:04:59 2026-06-02 13:04:59 2026-06-03 03:56:38 0000-00-00 00:00:00 2023 0 0 Nasl. z nasl. zaslona; Opis vira z dne 25. 5. 2026; str. 1-13 no. 17, [article no.] e161170 Vol. 133 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.9 1558-8238 10.1172/JCI161170 279244035 RAZ_Kanjana_Korawit_2023.pdf RAZ_Kanjana_Korawit_2023.pdf 1 11B53E586C9CBE4F8F4640D6432629CA 2cf4cb4a48488092aa088c300e909248cfcb5f51a3ff81f0d345012cd0457007 0af4417f-5e73-11f1-8e51-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44533 https://www.jci.org/articles/view/161170 1 e851a382-5e72-11f1-8e51-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=44532 Univerzitetni klinični center Ljubljana 0 0 0