Di Sante Gabriele, Gremese Elisa, Tolusso Barbara, Cattani Paola, Di Mario Clara, Marchetti Simona, Alivernini Stefano, Tredicine Maria, Petricca Luca, Palucci Ivana, Camponeschi Chiara, Aragon Virginia, Gambotto Andrea, Ria Francesco, Ferraccioli Gianfranco
Section of General Pathology, Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy.
Division of Rheumatology, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Rome, Italy.
Front Med (Lausanne). 2021 Aug 17;8:671018. doi: 10.3389/fmed.2021.671018. eCollection 2021.
(; now ) 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). We tested the presence of 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 by Coll-specific T cells in HLA-DRB104 RA patients, by T-cell receptor (TCR) beta chain spectratyping and T-cell phenotyping. DNA was present in 57.4% of the tooth crevicular fluids of RA patients and in 31.6% of controls. Anti- 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 virulence-associated trimeric autotransporter peptide (VtaA10), homologous to human Coll or co-cultured with live . In both conditions, the expanded TCR repertoire overlapped with Coll and led to the production of IL-17. We show that the DNA of an infectious agent (), not previously described as pathogen in humans, is present in most patients with RA and that an peptide is able to activate T cells specific for Coll, likely inducing or maintaining a molecular mimicry mechanism. 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.
（；现在）是一种可导致猪严重关节炎的感染因子，与2型胶原蛋白（Coll）的261 - 273位残基具有序列相似性，Coll可能是类风湿关节炎（RA）中的自身抗原。我们检测了关节炎患者（RA和其他外周关节炎）及健康对照者龈沟液、滑液和组织中16S核糖体RNA的测序情况。此外，我们通过T细胞受体（TCR）β链谱型分析和T细胞表型分析，研究了HLA - DRB104 RA患者中Coll特异性T细胞对的交叉识别。在RA患者的57.4%的龈沟液和31.6%的对照者龈沟液中存在DNA。可检测到抗IgM和IgG滴度，且与疾病持续时间和患者年龄相关。用与人类Coll同源的毒力相关三聚体自转运肽（VtaA10）刺激外周血单个核细胞（PBMC），或与活的共同培养。在这两种情况下，扩增的TCR库与Coll重叠并导致IL - 17的产生。我们表明，一种以前未被描述为人类病原体的感染因子（）的DNA存在于大多数RA患者中，并且一种肽能够激活对Coll特异的T细胞，可能诱导或维持分子模拟机制。非人类感染因子的VtaA10与人类Coll之间的交叉反应性提示其参与RA的发病机制。这种机制在易感个体如具有共享表位的患者中似乎更为突出。
