Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti-Cyclic Citrullinated Protein Antibody-Positive At-Risk Adults Without Arthritis
Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti-Cyclic Citrullinated Protein Antibody-Positive At-Risk Adults Without Arthritis
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DOI：
10.1001/jamanetworkopen.2019.5394
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发表时间：
2019-06-01
影响因子：
13.8
通讯作者：
Emery, Paul
中科院分区：
文献类型：
--
作者：
Mankia, Kulveer;Cheng, Zijian;Emery, Paul
重要性 类风湿性关节炎 (RA) 患者的牙周炎患病率有所增加，并且牙周病细菌可以瓜氨酸化蛋白质。因此，牙周炎可能是 RA 的引发因素，也是预防的目标。尚未对患有 RA 自身免疫但无关节炎的高危个体进行牙周病和牙周细菌的调查。目的 检查抗环瓜氨酸蛋白（抗 CCP）抗体阳性、无关节炎的高危个体中的牙周病和牙周病细菌。设计、设置和参与者这项横断面研究于 2015 年 4 月 27 日至 5 月在一家教学医院进行。 2017 年 12 月 8 日，在全国范围内招募了 48 名无关节炎的抗 CCP 阳性个体（CCP+高危人群）。当地招募了 26 名早期 RA (ERA) 患者和 32 名健康对照者。数据分析于 2017 年 6 月 1 日至 2017 年 12 月 1 日期间进行。 干预措施 使用超声检查进行牙周评估和关节检查。 主要结果和措施 与 ERA 患者以及年龄和吸烟情况匹配的健康个体相比，CCP+ 高危个体中患病牙周部位、临床牙周炎和牙周发炎表面积的患病率。对患病和健康牙周部位龈下菌斑的 DNA 进行双端测序，并对 DNA 进行分析。 结果 共有 48 名 CCP+ 高危个体（平均 [SD] 年龄，51.9 [11.4] 岁；31 [65%] 女性），26 名 ERA 患者（平均 [SD] 年龄，54.4 [16.7] 岁；14 [54%] 患者女性），以及 招募了 32 名健康个体（平均 [SD] 年龄，49.4 [15.3] 岁；19 [59%] 女性）。在 48 名 CCP+ 高危人群中，46 人超声检查未发现关节炎症。 35 名 CCP+ 高危个体 (73%)、12 名健康个体 (38%) 和 14 名 ERA 患者 (54%) 患有临床牙周炎。与健康个体相比，CCP+高危个体中存在疾病的牙周部位的中位数（四分位距）百分比更高（3.3%[0%-11.3%] vs 0% [0%-0.7%]），并且与 ERA 患者相似（1.1%[0%-13.1%]）。与健康个体相比，CCP+高危个体的中位（四分位距）牙周发炎表面积较高（221 mm(2) [81-504 mm(2)] vs 40 mm2 [12-205 mm(2)]）。与健康个体（效应值，3.00；95% CI，1.71-4.29）和 ERA 患者（效应值，2.14；95% CI，0.77-3.52）相比，CCP+高危患者的健康牙周部位牙龈卟啉单胞菌（但不包括放线菌聚集菌）相对丰度增加。结论和相关性 这项研究发现患病率有所增加 CCP+高危人群中牙周炎和牙龈卟啉单胞菌的发生率。这表明牙周炎和牙龈卟啉单胞菌与疾病的发生有关，并且可能成为 RA 预防性干预的目标。
IMPORTANCE The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA) and periodontopathic bacteria can citrullinate proteins. Periodontitis may, therefore, be an initiator of RA and a target for prevention. Periodontal disease and periodontal bacteria have not been investigated in at-risk individuals with RA autoimmunity but no arthritis.OBJECTIVE To examine periodontal disease and periodontopathic bacteria in anti-cyclic citrullinated protein (anti-CCP) antibody-positive at-risk individuals without arthritis.DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study took place at a teaching hospital from April 27, 2015, to May 8, 2017. Forty-eight anti-CCP-positive individuals without arthritis (CCP+ at-risk) were recruited nationally. Twenty-six patients with early RA (ERA) and 32 healthy control individuals were recruited locally. Data were analyzed between June 1, 2017, and December 1, 2017.INTERVENTIONS Periodontal assessment and examination of joints using ultrasonography.MAIN OUTCOMES AND MEASURES Prevalence of diseased periodontal sites, clinical periodontitis, and periodontal inflamed surface area in CCP+ at-risk individuals compared with patients with ERA and healthy individuals matched for age and smoking. Paired-end sequencing of DNA from subgingival plaque from diseased and healthy periodontal sites was performed and DNA was profiled and analyzed.RESULTS A total of 48 CCP+ at-risk individuals (mean [SD] age, 51.9 [11.4] years; 31 [65%] female), 26 patients with ERA (mean [SD] age, 54.4 [16.7] years; 14 [54%] female), and 32 healthy individuals (mean [SD] age, 49.4 [15.3] years; 19 [59%] female) were recruited. Of 48 CCP+ at-risk individuals, 46 had no joint inflammation on ultrasonography. Thirty-five CCP+ at-risk individuals (73%), 12 healthy individuals (38%), and 14 patients with ERA (54%) had clinical periodontitis. The median (interquartile range) percentage of periodontal sites with disease was greater in CCP+ at-risk individuals compared with healthy individuals (3.3%[0%-11.3%] vs 0% [0%-0.7%]) and similar to patients with ERA (1.1%[0%-13.1%]). Median (interquartile range) periodontal inflamed surface area was higher in CCP+ at-risk individuals compared with healthy individuals (221 mm(2) [81-504 mm(2)] vs 40 mm2 [12-205 mm(2)]). Patients with CCP+ at-risk had increased relative abundance of Porphyromonas gingivalis (but not Aggregatibacter actinomycetemcomitans) at healthy periodontal sites compared with healthy individuals (effect size, 3.00; 95% CI, 1.71-4.29) and patients with ERA (effect size, 2.14; 95% CI, 0.77-3.52).CONCLUSIONS AND RELEVANCE This study found increased prevalence of periodontitis and P gingivalis in CCP+ at-risk individuals. This suggests periodontitis and P gingivalis are associated with disease initiation and could be targets for preventive interventions in RA.