Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis
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Author
Di Sante, Gabriele
Gremese, Elisa
Tolusso, Barbara
Cattani, Paola
Di Mario, Clara
Marchetti, Simona
Alivernini, Stefano
Tredicine, Maria
Petricca, Luca
Palucci, Ivana
Camponeschi, Chiara
Gambotto, Andrea
Ria, Francesco
Ferraccioli, Gianfranco
Publication date
2021-08-17ISSN
2296-858X
Abstract
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
11
Publisher
Frontiers Media
Is part of
Frontiers in Medicine
Citation
Di Sante, Gabriele, Elisa Gremese, Barbara Tolusso, Paola Cattani, Clara Di Mario, Simona Marchetti, and Stefano Alivernini et al. 2021. "Haemophilus Parasuis (Glaesserella Parasuis) As A Potential Driver Of Molecular Mimicry And Inflammation In Rheumatoid Arthritis". Frontiers In Medicine 8. doi:10.3389/fmed.2021.671018.
Program
Sanitat Animal
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- ARTICLES CIENTÍFICS [2555]
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