由自體免疫抗體觀點探討牙周病病菌與紅斑性狼瘡之關聯

The Association of Periodontal Pathogens and Systemic Lupus Erythematosus from the Viewpoint of Autoimmune Antibodies

王雅麗(Ya-Li Wang)

指導教授 ： 陳漪紋

共同指導教授 ： 郭彥彬

國立臺灣大學/牙醫專業學院/臨床牙醫學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.10308

摘要

研究背景：文獻報告指出紅斑性狼瘡病人的血清中常能檢驗出自體免疫抗體抗心磷脂抗體的存在。抗心磷脂抗體屬於抗磷脂抗體中的一群，主要和血栓的產生有關係。當抗心磷脂抗體要與心磷脂結合時需要磷脂結合蛋白β2 Glycoprotein I 的存在才能和心磷脂結合。近年來也有研究指出β2 Glycoprotein I 上的TLRVYK蛋白序列其實才是抗心磷脂抗體的target antigen。此外，β2 Glycoprotein I 有抑制凝血的功能，若自體免疫抗體和β2 Glycoprotein I結合則會抑制其凝血的功能，進而促進血栓的形成。另一方面，牙周致病菌具有和TLRVYK類似的蛋白序列有可能在感染牙周致病菌的病人身上引發自體免疫抗體的產生，因此本實驗將從自體免疫抗體的角度探討牙周病致病菌的存在與紅斑性狼瘡疾病嚴重程度的相關性。
材料與方法：59位紅斑性狼瘡病人及35位健康者參與實驗。所有受試者皆接受臨床牙周檢查，並收集其唾液，牙菌斑以及血清。紅斑性狼瘡病人依據“systemic lupus erythematosus disease activity index” (SLEDAI)分為疾病活性不穩定31位，穩定28位。爾後利用聚合酶鏈鎖反應偵測唾液及牙菌斑中牙周病致病菌Porphyromonas gingivalis （P. gingivalis）， Treponema denticola （T. denticola），Aggregatibacter actinomycetemcomitans （A. actimomycetemcomitans）的存在，並透過酵素免疫分析法測量其血清中抗心磷脂抗體，以及anti-β2 Glycoprotein I antibodies的含量。再將蒐集的資料進一步進行統計分析。
結果：相較於健康者，紅斑性狼瘡病人的牙周病盛行率較高，anti-β2 Glycoprotein I antibodies 也比較高，並具有統計上的差異性。研究結果也發現無論是不穩定或是穩定紅斑性狼瘡病人，其牙周附連喪失、牙周囊袋深度都比健康者嚴重。另一方面，雖然未達統計上的顯著性，不穩定紅斑性狼瘡疾病的病人若患有牙周病，或是有牙周致病菌的存在都會使血清中傾向於檢測出較高的anti-β2 Glycoprotein I antibodies 。尤其是同時感染兩種細菌時更有抗體值升高的趨勢，並達到統計上的差異性。
結論：本實驗發現紅斑性狼瘡疾病活性不穩定的病人其牙周病破壞與升高的anti-β2 Glycoprotein I antibodies相關，牙周致病菌P. gingivalis和T. denticola可能會引發自體免疫抗體的產生。因此對於臨床上anti-β2 Glycoprotein I antibodies較高的紅斑性狼瘡病人可以建議其接受牙周檢查，若患有牙周病則透過牙周病治療減少牙周致病菌的存在，改善牙周的健康降低由感染而引發的自體免疫抗體產生，或許能改善紅斑性狼瘡病人可能會面臨的臨床併發症。

關鍵字

紅斑性狼瘡 ； 抗心磷脂抗體 ； 牙周病 ； 牙周病致病菌 ； β2 Glycoprotein I

並列摘要

Introduction: It was reported Systemic Lupus Erythematosus (SLE) patients exhibited higher anti-cardiolipin (anti-CL) antibodies, a class of anti-phospholipid antibodies associated with thrombosis. Anti-CL antibodies required the presence of the plasma phospholipid binding protein, β2-Glycoprotein I (β2GPI), in order to bind cardiolipin molecule. β2-Glycoprotein I has been considered as the actual target antigen for autoimmune antibodies. Pathogenic anti-cardiolipin and anti- β2GPI antibodies could be induced by immunizing mice with Hemophilus influenzae or Neisseria gonorrheae, which bear peptide sequences homologous to the TLRVYK peptide of β2GPI. Periodontal bacteria also bear homologous peptide of TLRVYK; therefore, we hypothesize that periodontal bacteria might induce anti-CL or anti-β2GPI antibodies production through molecular mimicry.
Materials and Methods: 59 SLE patients and 35 healthy subjects were recruited in this study, and all subjects received periodontal examinations. The disease activity of SLE was classified into mild and moderate to severe groups based on the “systemic lupus erythematosus disease activity index” (SLEDAI). The presence of Porphyromonas gingivalis (P. gingivalis), Treponema denticola（T. denticola）and Aggregatibacter actinomycetemcomitans（A. actimomycetemcomitans）in saliva and plaque sample was detected by polymerase chain reaction. Serum Anti-CL and anti-β2GPI antibodies were examined using the enzyme-linked immunosorbent assay.
Results: Both two groups of SLE patients showed higher prevalence of periodontitis, more severe periodontal destruction and increased titers of serum anti-β2GPI antibodies compared with healthy subjects. Moderate to severe SLE patients with periodontitis seemed to exhibited higher anti-β2GPI antibodies than those without periodontitis. The level of anti-β2GPI antibodies was significantly higher in moderate to severe SLE patients who harboured T. denticola and P. gingivalis intra orally.
Conclusion: Elevated anti-β2GPI antibodies was associated with periodontal severity, especially in moderate to severe SLE patients. T. denticola and P. gingivalis might serve as exogenous antigens that elicit anti-β2GPI antibodies production. Anti-β2GPI antibodies might be used as a biomarker to detect periodontal diseases in SLE patients.

並列關鍵字

Systemic lupus erythematosus ； anti-cardiolipin antibody ； β2Glycoprotein I ； periodontal disease ； periodontal pathogen

參考文獻

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