Manoil Daniel, Courvoisier Delphine S, Gilbert Benoit, Möller Burkhard, Walker Ulrich A, Muehlenen Ines Von, Rubbert-Roth Andrea, Finckh Axel, Bostanci Nagihan
Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Rheumatology, Department of Internal Medicine Specialties, University Hospitals of Geneva, Geneva.
Rheumatology (Oxford). 2021 Oct 2;60(10):4755-4764. doi: 10.1093/rheumatology/keab097.
To examine whether serum antibodies against selected periodontal pathogens are associated with early symptoms of RA development in healthy individuals at risk of developing the disease.
Within an ongoing study cohort of first-degree relatives of patients with RA (RA-FDRs), we selected four groups corresponding to specific preclinical phases of RA development (n = 201). (i) RA-FDR controls without signs and symptoms of arthritis nor RA-related autoimmunity (n = 51); (ii) RA-FDRs with RA-related autoimmunity (n = 51); (iii) RA-FDRs with inflammatory arthralgias without clinical arthritis (n = 51); and (iv) RA-FDRs who have presented at least one swollen joint ('unclassified arthritis') (n = 48). Groups were matched for smoking, age, sex and shared epitope status. The primary outcome was IgG serum levels against five selected periodontal pathogens and one commensal oral species assessed using validated-in-house ELISA assays. Associations between IgG measurements and preclinical phases of RA development were examined using Kruskal-Wallis or Mann-Whitney tests (α = 0.05).
None of the IgGs directed against individual periodontal pathogens significantly differed between the four groups of RA-FDRs. Further analyses of cumulated IgG levels into bacterial clusters representative of periodontal infections revealed significantly higher IgG titres against periodontopathogens in anti-citrullinated protein antibodies (ACPA)-positive RA-FDRs (P = 0.015). Current smoking displayed a marked trend towards reduced IgG titres against periodontopathogens.
Our results do not suggest an association between serum IgG titres against individual periodontal pathogens and specific preclinical phases of RA development. However, associations between cumulative IgG titres against periodontopathogens and the presence of ACPAs suggest a synergistic contribution of periodontopathogens to ACPA development.
研究针对特定牙周病原体的血清抗体是否与有患类风湿关节炎（RA）风险的健康个体的RA早期症状相关。
在一项正在进行的RA患者一级亲属（RA-FDRs）队列研究中，我们选择了与RA发展的特定临床前期相对应的四组（n = 201）。（i）无关节炎体征和症状且无RA相关自身免疫的RA-FDR对照组（n = 51）；（ii）有RA相关自身免疫的RA-FDRs（n = 51）；（iii）有炎性关节痛但无临床关节炎的RA-FDRs（n = 51）；以及（iv）出现至少一个肿胀关节（“未分类关节炎”）的RA-FDRs（n = 48）。根据吸烟、年龄、性别和共同表位状态对各组进行匹配。主要结局是使用经过内部验证的酶联免疫吸附测定（ELISA）法评估的针对五种选定牙周病原体和一种口腔共生菌的IgG血清水平。使用Kruskal-Wallis检验或Mann-Whitney检验（α = 0.05）来研究IgG测量值与RA发展临床前期之间的关联。
四组RA-FDRs中，针对单个牙周病原体的IgG均无显著差异。将累积IgG水平进一步分析为代表牙周感染的细菌簇后发现，抗瓜氨酸化蛋白抗体（ACPA）阳性的RA-FDRs中针对牙周病原体的IgG滴度显著更高（P = 0.015）。当前吸烟表现出针对牙周病原体的IgG滴度降低的明显趋势。
我们的结果并不表明针对单个牙周病原体的血清IgG滴度与RA发展的特定临床前期之间存在关联。然而，针对牙周病原体的累积IgG滴度与ACPA的存在之间的关联表明牙周病原体对ACPA发展有协同作用。
