Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis
Di Sante, Gabriele (Università Cattolica del Sacro Cuore. Department of Translational Medicine and Surgery)
Gremese, Elisa (Università Cattolica del Sacro Cuore. Division of Rheumatology)
Tolusso, Barbara (Fondazione Policlinico Universitario Agostino Gemelli-IRCCS. Division of Rheumatology)
Cattani, Paola (Università Cattolica del S. Cuore. Dipartimento di Scienze Biotecnologiche di Base)
Di Mario, Clara (Università Cattolica del Sacro Cuore. Division of Rheumatology)
Marchetti, Simona (Fondazione Policlinico Universitario Agostino Gemelli-IRCCS)
Alivernini, Stefano (Fondazione Policlinico Universitario Agostino Gemelli-IRCCS)
Tredicine, Maria (Università Cattolica del Sacro Cuore. Department of Translational Medicine and Surgery)
Petricca, Luca (Fondazione Policlinico Universitario Agostino Gemelli-IRCCS)
Palucci, Ivana (Università Cattolica del S. Cuore. Dipartimento di Scienze Biotecnologiche di Base)
Camponeschi, Chiara (Università Cattolica del Sacro Cuore. Department of Translational Medicine and Surgery)
Aragon, Virginia (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal)
Gambotto, Andrea (University of Pittsburgh School of Medicine)
Ria, Francesco (Fondazione Policlinico Universitario Agostino Gemelli-IRCCS)
Ferraccioli, Gianfranco (Università Cattolica del Sacro Cuore)

Fecha:	2021
Resumen:	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 (Coll), 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 Coll-specific T cells in HLA-DRB1 * 04 pos 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 (VtaA10), homologous to human Coll or co-cultured with live Hps. In both conditions, the expanded TCR repertoire overlapped with Coll 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 Coll, likely inducing or maintaining a molecular mimicry mechanism. Conclusion: The cross-reactivity between VtaA10 of a non-human infectious agent and human Coll suggests an involvement in the pathogenesis of RA. This mechanism appears emphasized in predisposed individuals, such as patients with shared epitope.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Haemophilus (Glaesserella) parasuis ; Molecular mimicry ; Rheumatoid arthritis ; Host-pathogen interaction ; Cross-reactivity
Publicado en:	Frontiers in Medicine, Vol. 8 (august 2021) , ISSN 2296-858X

DOI: 10.3389/fmed.2021.671018
PMID: 34485325

11 p, 1.0 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
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