建立評估類風溼性關節炎病人之關節損壞程度的生物標誌

Develop Biomarkers for Assessing Joint Erosion of Rheumatoid Arthritis

羅婉臻(Wann-Cheng Lo)

指導教授 ： 林亮音

國立臺灣大學/醫學院/醫事技術學研究所/碩士(2005年)

https://doi.org/10.6342/NTU.2005.10296

摘要

類風溼性關節炎(Rheumatoid arthritis)為一種慢性、進行性以關節及其周圍組織侵犯為主的免疫疾病。早期通常為多發性、對稱性的關節炎，可引起關節的破壞與侵蝕，繼而造成關節的畸形與功能損傷，造成病人生活不便。傳統的檢查技術(包括serum CRP和ESR)，甚至影像方法(包括核磁共振與X-光照影)，皆無法提供區域性骨侵蝕或全身性骨骼流失的正確資訊。故在此研究當中，我們收集36位病人，分析其28處關節疾病活動度積分(DAS28)、X-光(Sharp score)、以及十個血清或尿液的生化指標。其中20位病人繼續追蹤九個月，進行四次核磁共振分析(骨侵蝕、骨髓水腫和滑膜炎)，發現核磁共振和X-光在四個時間點所偵測的骨侵蝕程度，在個別時間點並無明顯差異，代表在這九個月的追蹤期間，病人骨骼並無明顯變化。在此36位病人當中，DAS28與關節間隙狹窄 (JSN of Sharp score)存在著很高的相關性；同時，核磁共振的骨侵蝕與ERO也有高度相關。當分析基準點時的36位病人資料，則發現DAS28與CRP和PYD存在有有高度的相關性，Sharp scores與urinary CTX-I、YKL-40和PYD呈現高度相關。若進一步分析追蹤20位病人的個別資料，則發現其中有三位病人顯示相同的高相關性結果。在核磁共振影像方面， 20個病人在四個時間點所收集到的資料進行分析，則發現發現骨侵蝕高度相關於COMP、anti-CCP、osteocalcin和urinary CTX-II。骨髓水腫與osteocalcin和urinary CTX-II亦呈現高度之相關性，滑膜炎則是與urinary CTX-I相關。若進一步將所有時間數據整合，只剩下anti-CCP、osteocalcin、urinary CTX-I、YKL-40和urinary CTX-II與核磁共振影像具有相關性。

關鍵字

類風濕性關節炎 ； 核磁共振 ； 生物標誌 ； X-光

並列摘要

Rheumatoid arthritis (RA) is a chronic and potentially crippling disease characterized by systemic inflammation, bone erosion and joint tissue degradation. Laboratory tests (serum CRP and ESR) and even imaging methods (magnetic resonance imaging [MRI] and radiography) can not provide accurate information for local bone erosion or systemic bone loss. In the present study, thirty six RA patients were examined by disease activity using index 28 (DAS28), radiography (Sharp score), and measurement of ten biomarkers. The Sharp scores and MRI images were carefully scored. Twenty patients of thirty-six patients were continuously followed-up for 9 month periods. The results showed no significant difference of data at the four time points in the 20 patients. However, DAS28 showed clear correlations with joint space narrowing [JSN] of Sharp scores and MRI edema, while MRI erosion scores was correlated well with erosion of Sharp score [ERO] on radiography. Further investigation of data at baseline of 36 patients suggested that CRP and pyridinoline [PYD] can also be correlated well with DAS28, meanwhile urinary C-terminal telopeptide of type I collagen [CTX-I], YKL-40 and PYD demonstrated good correlations with Sharp score. The individual data of three RA patients, collected during the following six months, confirmed this high correlation between PYD, YKL-40 and Sharp scores. In MRI features at four time points in 20 patients, close relationships have also been found in between “erosions” and cartilage oligomeric matrix protein [COMP], anti-cyclic citrullinated peptide antibody [CCP], osteocalcin and urinary C-terminal telopeptide of type II collagen [CTX-II]; “edema” and osteocalcin and urinary CTX-II; “synovitis" and urinary CTX-I.

並列關鍵字

Rheumatoid Arthritis ； RA ； biomarkers ； MRI ； radiography ； bone erosion

參考文獻

American College of Rheumatology “Patient Education” http://www.rheumatology.org/public/factsheets/ra.asp (April 2003)

Anderson JJ, Wells G, Verhoeven AC, et al. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 2000; 43: 22-9.

Bathon JM, Martin RW, Fleischmann RM, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000; 343: 1586-93.

Berger CE, Krönera AH, Minai-Pour MB et al. Biochemical markers of bone metabolism in bone marrow edema syndrome of the hip. Bone. 2003; 33: 346-51.

Boers M, Verhoeven AC, Markusse HM, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997; 350: 309-18.