| Abstract: | 因此，我們希望建?一個以醫院為基礎的僵直性脊椎炎病患世代，?分析台灣僵直性脊椎炎?床??病學之現況，探討病患的疾病自然史，並且評估巴斯僵直性脊椎炎疾病活動?表 (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]) 與發炎指標C-反應蛋白 (C-reactive protein [CRP]) 之關係，以訂?出判斷僵直性脊椎炎疾病活動期的最佳?點分?。進一步地，骨質?失是僵直性脊椎炎症?之一，而造骨細胞 (osteoblast) 與蝕骨細胞 (osteoclast) 的作用一旦失衡時，可造成骨質的?常。自體免疫耐受性(immunological self-tolerance) 之失衡也已被報告相關於自體免疫疾病的發生，計畫性細胞死亡-1 (programmed cell death 1 [PD-1]) 與其配位基-1 (PD-L1) 及配位基-2 (PD-L2)、第四?細胞毒?性T ?巴抗原 (cytotoxic T lymphocyte antigen-4 [CTLA-4]) 與?巴?氨酸磷酸? (lymphoid tyrosine phosphatase [LYP]) 在自體免疫耐受性平衡上扮演著關鍵的角色。然而，骨骼重塑模式之細胞核因子kB 接受器活化因子 (receptor activator of nuclear factor kappa B [RANK])、細胞核因子kB 配位體接受器活化因子 (receptor activator for nuclear factor kappa B ligand [RANKL])、和蝕骨細胞抑制因子 (osteoprotegerin [OPG]) 基因，以及自體免疫耐受性相關基因 (PD-1、PD-L1、PD-L2、 CTLA-4 與蛋白質?氨酸磷酸?N22 [protein tyrosine phosphatase, nonreceptor 22 [PTPN22]]) 於僵直性脊椎炎中之分子角色是?清楚的。我們將以三?時間收集900 名僵直性脊椎炎病患，問卷將被執?以獲取所有病患的人口學資?及?床特徵，巴斯僵直性脊椎炎疾病活動?表 (BASDAI)、巴斯僵直性脊椎炎功能?表 (Bath Ankylosing Spondylitis Functional Index [BASFI])、巴斯僵直性脊椎炎整體評分 (Bath Ankylosing Spondylitis Global Score [BAS-G])、?學檢查、血液發炎指標、HLA-B27 基因、骨形成標記也將被測?。接續，我們將以病?對照研究?評估骨骼重塑模式之RANK、RANKL 和OPG 基因，以及自體免疫耐受性相關基因 (PD-1、PD-L1、PD-L2、CTLA-4 與PTPN22) 是否相關於僵直性脊椎炎的發生及其?床表徵。?齡及性別配對的對照也將被納入研究中，聚合?鏈鎖反應-限制酵素片段長?多形性 (polymerase chain reaction-restriction fragment length polymorphism) 將被用以判定基因型。我們的結果將有助於瞭解僵直性脊椎炎發病與進展的可能機制。
Relevant factors that influence the disease occurrence and progression of ankylosing spondylitis (AS) are poorly understood because of the heterogeneous nature of AS, long disease duration, and lack of appropriate and valid measuring instruments. Therefore, we desire to establish a hospital-based cohort of patients with AS, and to analyze current status of clinical epidemiology of AS in Taiwan; to explore natural history of AS patients; and to establish the best cutoff for discriminating between disease active stage and inactive stage in AS, by evaluating the relationship of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP). Furthermore, bone loss was one of the symptoms reported in AS. When the balance between osteoblasts and osteoclasts was disrupted, abnormalities in bone mineral would occur. Imbalance of immunological self-tolerance has also been reported to be associated with the occurrence of autoimmune diseases. Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2, cytotoxic T lymphocyte antigen-4 (CTLA-4) and lymphoid tyrosine phosphatase (LYP) act as critical roles on the balance of immunological self-tolerance. However, the molecular roles of receptor activator of nuclear factor kappa B (RANK), receptor activator for nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) genes on bone remodeling; and related genes (PD-1, PD-L1, PD-L2, CTLA-4 and protein tyrosine phosphatase, nonreceptor 22 [PTPN22]) of immunological self-tolerance in AS development remain unclear. We will collect 900 AS patients in next 3 years. Questionnaires will be administered to all patients on demographic data and clinical features. The BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Global Score (BAS-G), anthropometric indicators, blood inflammation indicators, HLA-B27 status, and bone formation markers will also be measured. Subsequently, we will conduct a case-control study to evaluate the association between occurrence and clinical features of AS and RANK, RANKL and OPG genetic polymorphisms on bone remodeling; and related genes (PD-1, PD-L1, PD-L2, CTLA-4 and protein tyrosine phosphatase, nonreceptor 22 [PTPN22]) of immunological self-tolerance. Age and gender-matched controls will be recruited in the study. Polymerase chain reaction-restriction fragment length polymorphism will be applied to identify the genotypes. Our results will provide insights into the possible mechanism of AS occurrence and development. |
