Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis
Background:Haemophilus parasuis (Hps; now Glaesserella parasuis) is an infectious agent that causes severe arthritis in swines and shares sequence similarity with residues 261–273 of collagen type 2 (Coll261−273), a possible autoantigen in rheumatoid arthritis (RA).Objectives/methods: We tested the...
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Frontiers Media S.A.
2021-08-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.671018/full |
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doaj-579273deeeb247878bc381ac0e5f2208 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gabriele Di Sante Elisa Gremese Elisa Gremese Barbara Tolusso Paola Cattani Paola Cattani Clara Di Mario Simona Marchetti Stefano Alivernini Maria Tredicine Luca Petricca Ivana Palucci Ivana Palucci Chiara Camponeschi Virginia Aragon Andrea Gambotto Andrea Gambotto Andrea Gambotto Francesco Ria Francesco Ria Gianfranco Ferraccioli |
spellingShingle |
Gabriele Di Sante Elisa Gremese Elisa Gremese Barbara Tolusso Paola Cattani Paola Cattani Clara Di Mario Simona Marchetti Stefano Alivernini Maria Tredicine Luca Petricca Ivana Palucci Ivana Palucci Chiara Camponeschi Virginia Aragon Andrea Gambotto Andrea Gambotto Andrea Gambotto Francesco Ria Francesco Ria Gianfranco Ferraccioli Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis Frontiers in Medicine haemophilus (Glaesserella) parasuis molecular mimicry rheumatoid arthritis host-pathogen interaction cross-reactivity |
author_facet |
Gabriele Di Sante Elisa Gremese Elisa Gremese Barbara Tolusso Paola Cattani Paola Cattani Clara Di Mario Simona Marchetti Stefano Alivernini Maria Tredicine Luca Petricca Ivana Palucci Ivana Palucci Chiara Camponeschi Virginia Aragon Andrea Gambotto Andrea Gambotto Andrea Gambotto Francesco Ria Francesco Ria Gianfranco Ferraccioli |
author_sort |
Gabriele Di Sante |
title |
Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis |
title_short |
Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis |
title_full |
Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis |
title_fullStr |
Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis |
title_full_unstemmed |
Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis |
title_sort |
haemophilus parasuis (glaesserella parasuis) as a potential driver of molecular mimicry and inflammation in rheumatoid arthritis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2021-08-01 |
description |
Background:Haemophilus parasuis (Hps; now Glaesserella parasuis) is an infectious agent that causes severe arthritis in swines and shares sequence similarity with residues 261–273 of collagen type 2 (Coll261−273), a possible autoantigen in rheumatoid arthritis (RA).Objectives/methods: We tested the presence of Hps 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 Hps by Coll261−273-specific T cells in HLA-DRB1*04pos RA patients, by T-cell receptor (TCR) beta chain spectratyping and T-cell phenotyping.Results:Hps DNA was present in 57.4% of the tooth crevicular fluids of RA patients and in 31.6% of controls. Anti-Hps 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 Hps virulence-associated trimeric autotransporter peptide (VtaA10755−766), homologous to human Coll261−273 or co-cultured with live Hps. In both conditions, the expanded TCR repertoire overlapped with Coll261−273 and led to the production of IL-17.Discussion: We show that the DNA of an infectious agent (Hps), not previously described as pathogen in humans, is present in most patients with RA and that an Hps peptide is able to activate T cells specific for Coll261−273, likely inducing or maintaining a molecular mimicry mechanism.Conclusion: The cross-reactivity between VtaA10755−766 of a non-human infectious agent and human Coll261−273 suggests an involvement in the pathogenesis of RA. This mechanism appears emphasized in predisposed individuals, such as patients with shared epitope. |
topic |
haemophilus (Glaesserella) parasuis molecular mimicry rheumatoid arthritis host-pathogen interaction cross-reactivity |
url |
https://www.frontiersin.org/articles/10.3389/fmed.2021.671018/full |
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doaj-579273deeeb247878bc381ac0e5f22082021-08-17T06:52:24ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-08-01810.3389/fmed.2021.671018671018Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid ArthritisGabriele Di Sante0Elisa Gremese1Elisa Gremese2Barbara Tolusso3Paola Cattani4Paola Cattani5Clara Di Mario6Simona Marchetti7Stefano Alivernini8Maria Tredicine9Luca Petricca10Ivana Palucci11Ivana Palucci12Chiara Camponeschi13Virginia Aragon14Andrea Gambotto15Andrea Gambotto16Andrea Gambotto17Francesco Ria18Francesco Ria19Gianfranco Ferraccioli20Section of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyDivision of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Rome, ItalyDivision of Rheumatology, Università Cattolica del Sacro Cuore, Rome, ItalyDivision of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Rome, ItalyDipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, ItalyDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Sezione di Microbiologia, Università Cattolica del S. Cuore, Rome, ItalyDivision of Rheumatology, Università Cattolica del Sacro Cuore, Rome, ItalyDipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, ItalyDivision of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Rome, ItalySection of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyDivision of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Rome, ItalyDipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, ItalyDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Sezione di Microbiologia, Università Cattolica del S. Cuore, Rome, ItalySection of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyInstitut de Recerca i Tecnologies Agroalimentaries, Centre de Recerca en Sanitat Animal (CReSA IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, SpainDepartment of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesSection of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, ItalyDipartimento di Scienze di laboratorio e infettivologiche, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy0Università Cattolica del Sacro Cuore, Rome, ItalyBackground:Haemophilus parasuis (Hps; now Glaesserella parasuis) is an infectious agent that causes severe arthritis in swines and shares sequence similarity with residues 261–273 of collagen type 2 (Coll261−273), a possible autoantigen in rheumatoid arthritis (RA).Objectives/methods: We tested the presence of Hps 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 Hps by Coll261−273-specific T cells in HLA-DRB1*04pos RA patients, by T-cell receptor (TCR) beta chain spectratyping and T-cell phenotyping.Results:Hps DNA was present in 57.4% of the tooth crevicular fluids of RA patients and in 31.6% of controls. Anti-Hps 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 Hps virulence-associated trimeric autotransporter peptide (VtaA10755−766), homologous to human Coll261−273 or co-cultured with live Hps. In both conditions, the expanded TCR repertoire overlapped with Coll261−273 and led to the production of IL-17.Discussion: We show that the DNA of an infectious agent (Hps), not previously described as pathogen in humans, is present in most patients with RA and that an Hps peptide is able to activate T cells specific for Coll261−273, likely inducing or maintaining a molecular mimicry mechanism.Conclusion: The cross-reactivity between VtaA10755−766 of a non-human infectious agent and human Coll261−273 suggests an involvement in the pathogenesis of RA. This mechanism appears emphasized in predisposed individuals, such as patients with shared epitope.https://www.frontiersin.org/articles/10.3389/fmed.2021.671018/fullhaemophilus (Glaesserella) parasuismolecular mimicryrheumatoid arthritishost-pathogen interactioncross-reactivity |