Oluwagbemigun Kolade, Yucel-Lindberg Tülay, Dietrich Thomas, Tour Gregory, Sherina Natalia, Hansson Monika, Bergmann Manuela, Lundberg Karin, Boeing Heiner
Nutritional Epidemiology, Department of Nutrition and Food Sciences, University of Bonn, Endenicher Allee 19b, Bonn, 53115, Germany.
Periodontology Unit, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
Ther Adv Musculoskelet Dis. 2019 Nov 5;11:1759720X19883152. doi: 10.1177/1759720X19883152. eCollection 2019.
(P.g) is unique among pathogens due to its ability to generate citrullinated proteins in an inflammatory milieu, potentially mediating the loss of immune tolerance, the production of anticitrullinated protein antibodies (ACPAs), and subsequently the development of rheumatoid arthritis (RA). Based on this hypothesis, we set out to investigate whether P.g is linked to ACPAs in a well-characterized German population.
A total of 600 participants (292 women and 308 men with a mean age of 67 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam study were selected in 2013, and paired saliva and serum samples were collected. Salivary P.g DNA and serum anticyclic citrullinated peptide (anti-CCP2) levels were quantified by real-time polymerase chain reaction and anti-CCP2 enzyme-linked immunosorbent assay, respectively. In selected participants, additional ACPA fine-specificities were also analysed on a custom-made multiplex peptide array.
Among participants with C-reactive protein greater than 3.0 mg/l, a one-unit increase in P.g DNA was associated with an almost twofold increase in anti-CCP2 levels. Moreover, participants with high P.g DNA had on average approximately 2.8-times higher anti-CCP2 levels when compared with participants with low P.g DNA, (Holm-adjusted value = 0.01). Furthermore, citrullinated epitopes on α-enolase and vimentin were common ACPA reactivities among participants who also had high P.g DNA and elevated C-reactive protein.
Our study suggests that in specific subgroups of individuals with systemic inflammation, higher salivary P.g DNA is associated with elevated serum ACPA. These data support a role for P.g in the development of anticitrulline immunity.
牙龈卟啉单胞菌（P.g）在病原体中独具特性，因其能够在炎症环境中产生瓜氨酸化蛋白，这可能介导免疫耐受的丧失、抗瓜氨酸化蛋白抗体（ACPAs）的产生，进而导致类风湿性关节炎（RA）的发展。基于这一假设，我们着手在一个特征明确的德国人群中研究牙龈卟啉单胞菌是否与抗瓜氨酸化蛋白抗体相关。
2013年，从欧洲癌症与营养前瞻性调查 - 波茨坦研究中选取了600名参与者（292名女性和308名男性，平均年龄67岁），并收集了配对的唾液和血清样本。分别通过实时聚合酶链反应和抗环瓜氨酸肽2（anti-CCP2）酶联免疫吸附测定法定量唾液中的牙龈卟啉单胞菌DNA和血清抗环瓜氨酸肽水平。在选定的参与者中，还在定制的多重肽阵列上分析了额外的抗瓜氨酸化蛋白抗体精细特异性。
在C反应蛋白大于3.0mg/l的参与者中，牙龈卟啉单胞菌DNA增加一个单位与抗环瓜氨酸肽2水平几乎增加两倍相关。此外，与低牙龈卟啉单胞菌DNA的参与者相比，高牙龈卟啉单胞菌DNA的参与者平均抗环瓜氨酸肽2水平高出约2.8倍（霍尔姆校正P值 = 0.01）。此外，在牙龈卟啉单胞菌DNA含量高且C反应蛋白升高的参与者中，α - 烯醇化酶和波形蛋白上的瓜氨酸化表位是常见的抗瓜氨酸化蛋白抗体反应性。
我们的研究表明，在全身性炎症个体的特定亚组中，较高的唾液牙龈卟啉单胞菌DNA与血清抗瓜氨酸化蛋白抗体升高相关。这些数据支持牙龈卟啉单胞菌在抗瓜氨酸免疫发展中的作用。
