腫瘤壞死因子受器（TNFRI, TNFRII）：僵直性脊椎炎及類風濕性關節炎之生物標記及其表現

Circulating levels of tumor necrosis factor receptors I and II: biomarkers for ankylosing spondylitis and rheumatoid arthritis

目的：探討腫瘤壞死因子受器（TNFRI及TNFRII）在僵直性脊椎炎及類風濕性關節炎患者血清中的濃度，並比較此受器濃度與發炎指數（CRP及ESR）間的相關性。方法：本研究共納入80位僵直性脊椎炎患者，80位類風濕性關節炎患者，及40位健康受試者。利用流式細胞儀珠方式檢驗血清中第一型腫瘤壞死因子受器（TNFRI）及第二型腫瘤壞死因子受器（TNFRII）濃度，並將此濃度與C反應蛋白及紅血球沉降速率等發炎指數進行統計分析。結果：在僵直性脊椎炎及類風濕性關節炎患者血清中，第一型腫瘤壞死因子受器濃度均高於健康受試者（p < 0.001），但第二型腫瘤壞死因子受器濃度在此兩族群與控制組間的比較則沒有統計學上之意義。而在這兩種患者間，其第一型腫瘤壞死因子受器與陽性的C反應蛋白及紅血球沉降速率濃度有相關性（p值均小於0.001）。另外，在類風濕性關節炎組中，我們發現第一型腫瘤壞死因子受器濃度也跟陰性的C反應蛋白及紅血球沉降速率濃度有相關性（p值分別為0.009及0.004）。在分析第二型腫瘤壞死因子受器濃度時，只有類風濕性關節炎合併陽性C反應蛋白或紅血球沉降速率濃度的族群有達到統計學意義（p值分別為0.049及0.039）。結論：第一型腫瘤壞死因子受器與僵直性脊椎炎及類風濕性關節炎的發炎指數呈正相關，可能發展出更具專一性的生物製劑，同時也許能成為下一個有效監控疾病活性的生物標記。

Objective: To investigate serum concentrations of soluble tumor necrosis factor receptors I and II (TNFRI and TNFRII) in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) compared to healthy subjects. We further correlated the serum levels of TNFRI and TNFRII with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in AS and RA patients. Methods: We recruited 80 AS patients classified according to the European Spondyloarthropathy Study Group, 80 RA patients according to the American College of Rheumatology criteria, and 40 normal controls. TNFRI and TNFRII were measured by cytometric bead array. Results: Soluble TNFRI levels were higher in AS and RA patients (p < 0.001) than in the controls. There were no significant differences in serum levels of TNFRII between our patients and the controls. TNFRI was correlated with high CRP and high ESR in the RA and AS patients (all p < 0.001) compared with the controls. Furthermore, TNFRI was also correlated with normal CRP and ESR in the RA patients (p = 0.009 and 0.004, respectively). There were no significant differences except for the correlations found between high CRP and high ESR in the RA patients (p = 0.049 and 0.039, respectively). Conclusion: Increased levels of TNFRI were correlated with the inflammatory status in AS and RA patients, suggesting a preferable target for treatment. TNFRI but not TNFRII may be a more specific biomarker for AS and RA disease activity.