抗环瓜氨酸肽抗体阳性的类风湿关节炎高危人群及早期或已确诊的类风湿关节炎患者中Prevotella copri 抗体的相关性。
Association of Antibodies to Prevotella copri in Anti-Cyclic Citrullinated Peptide-Positive Individuals At Risk of Developing Rheumatoid Arthritis and in Patients With Early or Established Rheumatoid Arthritis.
机构信息
University of Colorado Denver.
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
出版信息
Arthritis Rheumatol. 2023 Apr;75(4):507-516. doi: 10.1002/art.42370. Epub 2023 Feb 22.
OBJECTIVE
Prevotella copri (P copri), a gut commensal, has been reported to be an immune-relevant organism in individuals with rheumatoid arthritis (RA). This study sought to evaluate anti-P copri (anti-Pc) antibody responses in our participant cohorts and to determine when in the natural history of RA such responses develop.
METHODS
We analyzed serum levels of immunoglobulin A (IgA) and IgG antibodies from a 27-kd protein of P copri (anti-Pc-p27), an immunogenic P copri protein, in study participants at risk of developing RA, participants who transitioned to RA, participants with early RA (<1 year of disease), and participants with established RA, with comparisons made to their matched controls. We also evaluated anti-Pc-p27 antibody levels in individuals stratified by RA-related autoantibody status.
RESULTS
Overall, participants with RA had significantly higher IgA anti-Pc-p27 antibody levels and trended toward higher IgG anti-Pc-p27 antibody levels compared with matched controls. When stratified by early versus established RA, participants with early RA had median IgG anti-Pc-p27 antibody levels that were overall higher, whereas median IgA anti-Pc-p27 antibody levels were statistically significantly higher in participants with established RA compared with their matched controls. In the autoantibody-specific analyses, the at-risk population with anti-cyclic citrullinated peptide (anti-CCP) antibodies, but not rheumatoid factor (RF), trended toward increased levels of IgG anti-Pc-p27. Additionally, RA participants who were seropositive for both CCP and RF had significantly increased levels of IgA anti-Pc-p27 antibodies and trended toward higher levels of IgG anti-Pc-p27 antibodies compared with matched controls.
CONCLUSION
Our findings support a potential etiologic role for P copri in both RA preclinical evolution and the subsequent pathogenesis of synovitis.
目的
共生菌Prevotella copri（P copri）已被报道为类风湿关节炎（RA）患者的免疫相关生物。本研究旨在评估我们的参与者队列中的抗 P copri（anti-Pc）抗体反应，并确定这些反应在 RA 的自然病史中何时发生。
方法
我们分析了处于发生 RA 风险中的研究参与者、发展为 RA 的参与者、早期 RA（<1 年疾病）的参与者和已确诊 RA 的参与者的血清中 27-kd P copri 蛋白（anti-Pc-p27）的免疫球蛋白 A（IgA）和 IgG 抗体水平，并与匹配的对照进行了比较。我们还评估了根据 RA 相关自身抗体状态分层的个体的抗-Pc-p27 抗体水平。
结果
总体而言，与匹配的对照相比，RA 患者的 IgA 抗-Pc-p27 抗体水平显著升高，且 IgG 抗-Pc-p27 抗体水平也呈升高趋势。当按早期与已确诊的 RA 分层时，与早期 RA 相比，早期 RA 患者的 IgG 抗-Pc-p27 抗体水平总体较高，而与匹配的对照相比，已确诊 RA 患者的 IgA 抗-Pc-p27 抗体水平具有统计学意义。在自身抗体特异性分析中，具有抗环瓜氨酸肽（anti-CCP）抗体但无类风湿因子（RF）的高危人群的 IgG 抗-Pc-p27 水平呈升高趋势。此外，同时为 CCP 和 RF 阳性的 RA 患者的 IgA 抗-Pc-p27 抗体水平显著升高，且 IgG 抗-Pc-p27 抗体水平也呈升高趋势，与匹配的对照相比。
结论
我们的发现支持 P copri 在 RA 临床前演变和随后的滑膜炎发病机制中具有潜在的病因作用。
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