2014-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/647504摘要：乾癬是一種常見的免疫相關慢性皮膚發炎性疾病，大概佔了總人口數的 2%。它被認為是一種自體免疫性疾病，與 T細胞的免疫調控異常有關。傳統的治療方式以照光、類固醇或免疫抑制劑治療，但是並不能完全消除病灶。近年新的生物製劑或標靶治療對於傳統療效反應不佳的病人有不錯的療效。牙周病是一種由細菌引起的慢性發炎反應的疾病，會造成牙周組織的破壞和齒槽骨的吸收，而 T細胞免疫反應亦被認為是牙周致病過程的關鍵角色。目前探討乾癬和牙周病關聯性的文獻報導仍有限，病例對照研究指出乾癬病人比健康者較容易罹患牙周病，至於機轉仍不清楚，推測可能與異常的免疫調節功能有關係。在前導實驗中，我們收集了 22位乾癬病人，和 33位健康者相較之下，發現病人普遍有牙齦炎或牙周病的問題。這兩種疾病的相似之處，可能都是來自於皮膚或牙齦溝內內局部的細菌引起發炎反應，加上異常的免疫功能導致。最近一篇報導指出風濕性關節炎病人接受生物製劑( anti-TNF-αtherapy )後，除了牙周囊袋以及牙齦發炎現象獲得改善之外，牙齦溝內 TNF-α的量亦顯著減少。但也有研究指出接受生物製劑的乾癬病人因為免疫力被抑制更容易受其他細菌感染。至目前為止，未有文獻報導乾癬病人接受生物製劑對牙周健康的影響。本研究的假設是乾癬病人接受生物拮抗劑治療會改善牙齦發炎狀況。本研究預計招募 120 位乾癬患者，乾癬病人在開始治療前一週、接受治療後六個月以及一年時接受牙科臨床檢查，以及拍攝四張 dental x-rays (vertical bitewing)。牙科臨床檢查包括初診全身疾病問卷調查，隨意選取上下各一個象限(half-mouth examination protocol) 做牙周檢查，並收集安靜時 0.5 ml唾液及牙齦溝液，分別以 real-time PCR 檢測唾液中牙周病致病菌(Porphyromonas gingivalis、Treponema denticola、Aggregatibacter actinomycetemcomitans、Ubiquitous primer、Tannerella forsythis) 數量，及以 ELISA檢測牙齦溝液中發炎因子濃度(TNF-α, IL-17, IL-12 /23 p40、LL-37)，將前述實驗數據在三個時間的前後變化與乾癬患者的臨床症狀做比較。本研究將有助於了解全身性免疫調節劑在牙周病治療的角色，並建立乾癬病人之牙周疾病的治療契機。 <br> Abstract: Psoriasis is a chronic, immunologically-mediated, inflammatory skin disease and biological therapies targeting tumor necrosis factor-α (TNF-α) and interleukin 17 (IL-17) , interleukin 12/23 (IL-12/23) have become increasing important agents in the management of psoriasis. TNF-α, IL-17, and IL-12/23 both play a major role in defense against infection. Periodontitis is a bacteria-caused chronic inflammatory disease. It will cause gingival recession and bone resorption. In severe periodontitis, teeth may exfoliate due to bone loss. Current understanding of the etiology of periodontitis implicates bacterial infection as the primary cause of the disease, while the pathology is the result of the interactions between pathogens and the host. The similarity of these two diseases may be due to the disregulation of immune response and the local trigger from microorganism on skin or gingival sulcus. Our preliminary data showed that most psoriasis patients had mild to severe periodontitis, compared to the healthy subjects; and even patients who received periodontitis couldn’t attenuate the severity of psoriasis.A recent study reported that rheumatoid arthritis patients receiving anti-TNF-α therapy improved the periodontal health. However, Large-scaled clinical trials and post-marking surveillance had shown these biological antagonist agents may increase susceptibility to other infections. Till now, the studies investigating the impact of biological antagonists on the periodontal health are limited. The aim of this study is to evaluate the impact of anti-TNF-α, anti-IL-17, and anti-IL-12/23 biologics treatment on periodontal health in psoriasis patients with periodontitis. Between 2014 and 2016, 120 consecutive patients with psoriasis who receive antagonists and have concerns of periodontal disease are enrolled in this project after informed consent. Patients themselves or their guardians sign informed consent for study protocols approved by the Institutional Review Board of National Taiwan University Hospital. Periodontal examination will be performed, saliva and gingival crevicular fluid will be collected for analysis of bacteria amount, inflammatory cytokines and antibacterial peptides, before and after biological antagonist treatments. This project will help understand the role of host modulatory agents in periodontal therapy, and also the appropriate periodontal intervention of psoriasis patients with periodontitis.乾癬牙周病生物製劑psoriasisperiodontitisbiological antagonist