{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:18:23Z","timestamp":1787026703311,"version":"build-2736575974"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007366","name":"Fondazione Italiana Sclerosi Multipla","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005743","name":"Universit\u00e0 Cattolica del Sacro Cuore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005743","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    <jats:italic>Haemophilus parasuis<\/jats:italic>\n                    (\n                    <jats:italic>Hps<\/jats:italic>\n                    ; now\n                    <jats:italic>Glaesserella parasuis<\/jats:italic>\n                    ) is an infectious agent that causes severe arthritis in swines and shares sequence similarity with residues 261\u2013273 of collagen type 2 (Coll\n                    <jats:sub>261\u2212273<\/jats:sub>\n                    ), a possible autoantigen in rheumatoid arthritis (RA).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objectives\/methods:<\/jats:bold>\n                    We tested the presence of\n                    <jats:italic>Hps<\/jats:italic>\n                    sequencing 16S ribosomal RNA in crevicular fluid, synovial fluids, and tissues in patients with arthritis (RA and other peripheral arthritides) and in healthy controls. Moreover, we examined the cross-recognition of\n                    <jats:italic>Hps<\/jats:italic>\n                    by Coll\n                    <jats:sub>261\u2212273<\/jats:sub>\n                    -specific T cells in HLA-DRB1\n                    <jats:sup>*<\/jats:sup>\n                    04\n                    <jats:sup>pos<\/jats:sup>\n                    RA patients, by T-cell receptor (TCR) beta chain spectratyping and T-cell phenotyping.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    <jats:italic>Hps<\/jats:italic>\n                    DNA was present in 57.4% of the tooth crevicular fluids of RA patients and in 31.6% of controls. Anti-\n                    <jats:italic>Hps<\/jats:italic>\n                    IgM and IgG titers were detectable and correlated with disease duration and the age of the patients. Peripheral blood mononuclear cells (PBMCs) were stimulated with\n                    <jats:italic>Hps<\/jats:italic>\n                    virulence-associated trimeric autotransporter peptide (VtaA10\n                    <jats:sub>755\u2212766<\/jats:sub>\n                    ), homologous to human Coll\n                    <jats:sub>261\u2212273<\/jats:sub>\n                    or co-cultured with live\n                    <jats:italic>Hps<\/jats:italic>\n                    . In both conditions, the expanded TCR repertoire overlapped with Coll\n                    <jats:sub>261\u2212273<\/jats:sub>\n                    and led to the production of IL-17.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Discussion:<\/jats:bold>\n                    We show that the DNA of an infectious agent (\n                    <jats:italic>Hps<\/jats:italic>\n                    ), not previously described as pathogen in humans, is present in most patients with RA and that an\n                    <jats:italic>Hps<\/jats:italic>\n                    peptide is able to activate T cells specific for Coll\n                    <jats:sub>261\u2212273<\/jats:sub>\n                    , likely inducing or maintaining a molecular mimicry mechanism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    The cross-reactivity between VtaA10\n                    <jats:sub>755\u2212766<\/jats:sub>\n                    of a non-human infectious agent and human Coll\n                    <jats:sub>261\u2212273<\/jats:sub>\n                    suggests an involvement in the pathogenesis of RA. This mechanism appears emphasized in predisposed individuals, such as patients with shared epitope.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2021.671018","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T02:52:27Z","timestamp":1629168747000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis"],"prefix":"10.3389","volume":"8","author":[{"given":"Gabriele","family":"Di Sante","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Gremese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Tolusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cattani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Di Mario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Marchetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Alivernini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tredicine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Petricca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Palucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Camponeschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Aragon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gambotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Ferraccioli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1111\/j.0105-2896.2009.00850.x","article-title":"Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis","volume":"233","author":"Wegner","year":"2010","journal-title":"Immunol Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1002\/art.11223","article-title":"Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis","volume":"48","author":"Rantap\u00e4\u00e4-Dahlqvist","year":"2003","journal-title":"Arthritis Rheum."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3236","DOI":"10.1074\/jbc.RA117.001013","article-title":"The interplay between citrullination and HLA-DRB1 polymorphism in shaping peptide binding hierarchies in rheumatoid arthritis","volume":"293","author":"Ting","year":"2018","journal-title":"J Biol Chem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/j.autrev.2017.09.002","article-title":"Is ACPA positivity the main driver for rheumatoid arthritis treatment?","volume":"16","author":"Alivernini","year":"2017","journal-title":"Pros and cons. 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