Associations between Elevated Anti-CCP Antibodies and Periodontal Destructions in Patients with Rheumatoid Arthritis: A Case-Control Study

類風溼性關節炎患者之抗環瓜胺酸化胜肽抗體與牙周病破壞程度之關連性：病例對照研究

錢之琳(Chih-Lin Chien) ； 楊甯雅(Ning-Ya Yang) ； 陳漪紋(Yi-Wen Chen)

《臺灣牙周病醫學會雜誌》 21卷4期 (2016/12) Pp. 327-338

https://doi.org/10.6121/TAP.2016.21.4.03

摘要

Rheumatoid arthritis (RA) is an inflammatory peripheral polyarthritis with unknown etiology. It typically leads to deformity through the stretching of tendons and ligaments, erosion of cartilage and bone, which were related to the balance between matrix metalloproteinase (MMP), tissue inhibitor of MMP (TIMP), and the expression of cytokines. The consequences are similar with the destructive patterns of periodontitis. The most unique character of RA is the appearance of anti-citrullinated protein/peptide antibodies (ACPA). Serum examination of anti-cyclic citrullinated peptide antibody (Anti-CCP antibody) could be one of the tools for its diagnosis and classification. Given inflammatory disease caused by microbial infection, periodontitis was proved relevant to rheumatoid arthritis not only the pattern of destruction but also the molecular basis of immunity arousal. Last but not least, Porphyromonas ginigivalis (P.g.), one of the periodontal pathogens, possess P.g.-peptidylarginine deiminase (PPAD). The enzyme functions on C-terminal arginine into citrulline as humans' does. Evidences suggest this could be a possible link between periodontitis and RA. The aim of this study was to investigate the associations between periodontitis and RA to establish a possible risk factor models. Material and methods: In this case-control study, we included 40 well-controlled RA patients as study group and 47 systemically healthy subjects as controls. All subjects received comprehensive periodontal examination, and peripheral venous blood withdrawal for detection of anti-CCP antibody by enzyme-linked immunosorbent assay (ELISA). Data were examined and analyzed with statistic methods of Mann-Whitney U-test and logistic regression. Results: The prevalence of periodontitis, inflammatory condition and periodontal destructions were more severe in RA group with statistically significant difference. We have observed a positive correlation in the percentage of PPD ≥ 4 mm with serum anti-CCP antibody concentration suggesting a possible association between periodontal inflammation and serum level of anti-CCP antibody. Meanwhile, there is statistically significant difference in serum level of anti-CCP antibody between RA group and healthy control group. Logistic regression revealed that the clinical attachment loss appears to be the risk factor of RA.

關鍵字

Anti-CCP antibody ； periodontitis ； clinical attachment loss ； rheumatoid arthritis

並列摘要

類風溼性關節炎是一種全身周邊大小多處關節慢性發炎的疾病，致病機轉仍不清楚，其特點為體內會出現抗瓜胺酸化蛋白抗體（anti-citrullinated protein/peptide antibodies, ACPA），典型症狀為關節的軟硬骨變形及侵蝕性破壞，與牙周病的疾病進程和破壞機轉雷同；最常被提出有關致病機轉的理論為瓜胺酸化蛋白大量產生，破壞免疫耐受性（immune tolerance）的平衡，引發強烈免疫反應造成發炎與破壞；而牙周致病菌P. gingivalis被發現同樣擁有能將人類纖維蛋白原（fibrinogen）與烯醇酶（α-enolase）轉化成瓜胺酸化蛋白的酵素，學者們開始正視兩病之間存在相互作用的可能性。本實驗目的為研究類風濕性關節炎病人的牙周病盛行率，及自體免疫抗體是否與牙周病嚴重程度有關。材料與方法：於本病例對照研究（case-controlstudy）中，共有40位類風溼性關節炎患者與47位健康者（非類風溼性關節炎患者）進行抽血檢查，以酵素免疫學分析（ELISA）檢測血液中自體免疫抗體，抗環瓜胺酸化胜肽抗體（anti-CCP antibody）濃度；所有受試者亦一併經由牙周病專科醫師進行全口牙周檢查，並根據美國牙周病學會的診斷分類方法來診斷受試者牙周病嚴重度；使用無母數檢定（Mann-Whitney U-test）與邏輯迴歸分析（logistic regression）等統計方式以分析與檢驗牙周病與類風溼性關節炎之間的相關性。結論：類風溼性關節炎病友的牙周病盛行率與牙周破壞比對照組嚴重，且有統計學上顯著差異；所有受試者在探測牙周囊袋深度（probing pocket depth, PPD） ≥ 4mm的百分比與抗環瓜胺酸化胜肽抗體之間，呈現統計學上顯著地正相關。類風溼性關節炎病友血液中抗環瓜胺酸化胜肽抗體濃度與對照組比較亦達到統計學上顯著地差異。迴歸分析結果顯示牙周附連喪失為類風溼性關節炎的重要風險因子。

並列關鍵字

抗環瓜胺酸化胜肽抗體 ； 牙周病 ； 牙周臨床附連喪失 ； 類風溼性關節炎