牙龈卟啉单胞菌抗体表明口腔感染、吸烟与类风湿关节炎发病风险基因之间存在相互作用。
Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology.
机构信息
Karolinska Institutet, Stockholm, Sweden.
University of Louisville School of Dentistry, Louisville, Kentucky.
出版信息
Arthritis Rheumatol. 2016 Mar;68(3):604-13. doi: 10.1002/art.39491.
OBJECTIVE
To investigate the role of the periodontal pathogen Porphyromonas gingivalis in the etiology of rheumatoid arthritis (RA) by analyzing the antibody response to the P gingivalis virulence factor arginine gingipain type B (RgpB) in relation to anti-citrullinated protein antibodies (ACPAs), smoking, and HLA-DRB1 shared epitope (SE) alleles in patients with periodontitis, patients with RA, and controls.
METHODS
Anti-RgpB IgG was measured by enzyme-linked immunosorbent assay in 65 periodontitis patients and 59 controls without periodontitis, and in 1,974 RA patients and 377 controls without RA from the Swedish population-based case-control Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study. Autoantibody status, smoking habits, and genetic data were retrieved from the EIRA database. Differences in antibody levels were examined using the Mann-Whitney U test. Unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs) for the association of anti-RgpB IgG with different subsets of RA patients.
RESULTS
Anti-RgpB antibody levels were significantly elevated in periodontitis patients compared to controls without periodontitis, in RA patients compared to controls without RA, and in ACPA-positive RA patients compared to ACPA-negative RA patients. There was a significant association between anti-RgpB IgG and RA (OR 2.96 [95% CI 2.00, 4.37]), which was even stronger than the association between smoking and RA (OR 1.37 [95% CI 1.07, 1.74]), and in ACPA-positive RA there were interactions between anti-RgpB antibodies and both smoking and the HLA-DRB1 SE.
CONCLUSION
Our study suggests that the previously reported link between periodontitis and RA could be accounted for by P gingivalis infection, and we conclude that P gingivalis is a credible candidate for triggering and/or driving autoimmunity and autoimmune disease in a subset of RA patients.
目的
通过分析牙周病原体牙龈卟啉单胞菌（P. gingivalis）毒力因子精氨酸牙龈蛋白酶 B（RgpB）的抗体反应与抗瓜氨酸蛋白抗体（ACPAs）、吸烟和 HLA-DRB1 共享表位（SE）等位基因之间的关系，探讨牙周炎患者、类风湿关节炎（RA）患者和对照者中 P. gingivalis 在 RA 发病机制中的作用。
方法
采用酶联免疫吸附试验（ELISA）检测 65 例牙周炎患者和 59 例无牙周炎对照者、1974 例 RA 患者和 377 例无 RA 的瑞典人群为基础的类风湿关节炎流行病学调查（EIRA）研究对照者的抗 RgpB IgG。从 EIRA 数据库中检索自身抗体状态、吸烟习惯和遗传数据。采用 Mann-Whitney U 检验比较抗体水平的差异。采用非条件逻辑回归计算抗 RgpB IgG 与不同亚组 RA 患者的关联的比值比（OR）及其 95%置信区间（95%CI）。
结果
与无牙周炎对照者相比，牙周炎患者、RA 患者和 ACPA 阳性 RA 患者的抗 RgpB 抗体水平显著升高。抗 RgpB IgG 与 RA 显著相关（OR 2.96 [95%CI 2.00，4.37]），这与吸烟和 RA 的相关性（OR 1.37 [95%CI 1.07，1.74]）甚至更强，在 ACPA 阳性 RA 中，抗 RgpB 抗体与吸烟和 HLA-DRB1 SE 之间存在交互作用。
结论
我们的研究表明，先前报道的牙周炎与 RA 之间的联系可能归因于 P. gingivalis 感染，我们得出结论，P. gingivalis 是引发和/或驱动 RA 患者亚群自身免疫和自身免疫性疾病的一个可信候选者。
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