2015-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645738摘要：分枝桿菌包含結核病(tuberculosis, TB) 的病原菌Mycobacteriumtuberculosis 外、也包括較不具致病性的非結核分枝桿菌(non-tuberculosismycobacterium, NTM)。雖然近年，台灣的TB 發生率逐漸下降，但仍是台灣死亡率最高的傳染病之一，而NTM 引起的感染症發生率與盛行率卻逐年增加。雖然多數NTM 屬於低致病性的病原菌，不常在人體造成疾病，然而，對於為什麼有些病患會罹患NTM 感染仍沒有答案。分枝桿菌屬於細胞內感染的病原菌，目前已知，由T 細胞及第一型細胞激素，如丙型干擾素(interferon-γ)所主導的細胞適應性免疫反應，於分枝桿菌感染的疾病控制上，扮演最重要的角色，例如，丙型干擾素自體抗體(interferon-γautoantibodies)已被發現是病患罹患瀰漫性NTM 感染的致病機轉之一。T 細胞受體(T-cell receptor，TCR)是T 細胞進行抗原辨認，啟動T 細胞免疫反應的關鍵，因此，TCR 缺陷可能也是重要的致病免疫機轉之一。TCR 免疫組庫(TCR immune repertoire)由眾多具特異性的TCR 所組成，是T 細胞發育過程中，藉由基因片段重組而來；為辨認各種致病病原，並避免自體免疫疾病，TCR 免疫組庫必須具有足夠的多樣性(diversity)及特異性(specificity)。近年來的研究已經發現，喪失TCR 免疫組庫型態的多樣性和老化及多種自體免疫疾病相關，並且在幾種癌症可發現具有特異性之TCR 免疫組庫型態。因此，分析分枝桿菌感染患者之TCR 免疫組庫型態，將有助於了解疾病之免疫病理機轉，並可能發展出具有疾病特異性的診斷方法。我們將收集罹患TB 及NTM 感染患者，進行丙型干擾素自體抗體檢測，並同時運用新一代multiplex PCR 及次世代高通量定序技術，檢測患者之TCR免疫組庫型態。將有助於更了解分枝桿菌感染之免疫病理機轉、並評估其診斷及疾病預測之價值。<br> Abstract: Infection cause by Mycobacterium tuberculosis and poorly pathogenicmycobacteria, nontuberculous mycobacteria (NTM), can be found in patients absenceof primary or secondary immune deficiency but the defect in immunity that confers apredisposition to it is still unclear. Human defense against these intracellular pathogensdepends on the action of cell-mediated immunity, effected by interactions between Tcells and associated type 1 cytokines, such as interferon-γ. Recently anti-interferon-γautoantibodies had been found to strongly associate with disseminated NTM disease.However, the impairment in T-cells might also play an important role.The T-cell receptor (TCR) immune repertoire is the sum total of functionallydiverse T cells. A global view of the entire diversity of TCR immune repertoire,especially third complementarity determining region (CDR3), able to provide aninsight, or a snapshot of T-cell medicated immunity and it may severe as an effectiveindicator for overall health status. A loss of diversity and diseases specific CDR3 hadbeen found in several cancer diseases. TCR immune repertoire analysis might also ableto decipher the immune response, provide improved understanding of the way bywhich the immune system disposes of infection and uncover the disease pathogenesisand susceptibility. Although the large diversity of the TCR immune repertoire isdifficult to discover, recent advance in next-generation sequencing technologies enablethe rapid sequencing of millions of DNA fragments with minimal bias.Therefore, we will concomitantly investigate the present of interferon-γautoantibodies and TCR immune repertoire with high throughput sequencing of CDR3sequence in NTM infection and tuberculosis. It might not only help to improveunderstanding of the possible defects associated with mycobacterium infections anddiscovery novel biomarkers that have diagnostic or prognostic potential but also couldbe used to further discovery potential therapeutic contexts.分枝桿菌結核病非結核分枝桿菌T 細胞受體免疫組庫MycobacteriaTuberculosisNontuberculous mycobacteriaT-cell receptor immune repertoire