TY - JOUR
T1 - Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis
AU - Di Sante, Gabriele
AU - Gremese, Elisa
AU - Tolusso, Barbara
AU - Cattani Franchi, Paola
AU - Di Mario, Clara
AU - Marchetti, Simona
AU - Alivernini, Stefano
AU - Tredicine, Maria
AU - Petricca, Luca
AU - Palucci, Ivana
AU - Camponeschi, Chiara
AU - Aragon, Virginia
AU - Gambotto, Andrea
AU - Ria, Francesco
AU - Ferraccioli, Gianfranco
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - cross-reactivity
KW - haemophilus (Glaesserella) parasuis
KW - host-pathogen interaction
KW - molecular mimicry
KW - rheumatoid arthritis
KW - cross-reactivity
KW - haemophilus (Glaesserella) parasuis
KW - host-pathogen interaction
KW - molecular mimicry
KW - rheumatoid arthritis
UR - http://hdl.handle.net/10807/183101
U2 - 10.3389/fmed.2021.671018
DO - 10.3389/fmed.2021.671018
M3 - Article
SN - 2296-858X
VL - 8
SP - N/A-N/A
JO - Frontiers in Medicine
JF - Frontiers in Medicine
ER -