High Heritability of Antimycobacterial Immunity in an Area of Hyperendemicity for Tuberculosis Disease
High Heritability of Antimycobacterial Immunity in an Area of Hyperendemicity for Tuberculosis Disease
复制标题
DOI：
10.1086/648611
复制
发表时间：
2010-01-01
影响因子：
6.4
通讯作者：
Schurr, Erwin
中科院分区：
文献类型：
--
作者：
Cobat, Aurelie;Gallant, Caroline J.;Schurr, Erwin
人类抗分枝杆菌免疫是结核病（TB）发病机制的重要组成部分，通常用于推断TB感染的存在。我们报告了肿瘤坏死因子α和干扰素γ（IFN-γ）体外分泌的高遗传性（>50%），以及全血对分枝杆菌攻击的反应中抗原特异性IFN-γ（+）CD 4（+）和IFN-γ（+）CD 8（+）细胞的频率。在主成分分析中，前3个成分解释了总方差的78%，与人类抗分枝杆菌免疫的多效性调节基因的作用一致。这些结果直接证明了宿主遗传学在结核感染免疫诊断基础的抗分枝杆菌免疫定量测量中所起的关键作用。
Human antimycobacterial immunity is a critical component of tuberculosis (TB) pathogenesis that is often used to infer the presence of TB infection. We report high heritability (>50%) for in vitro secretion of tumor necrosis factor alpha and interferon gamma (IFN-gamma), and the frequency of antigen-specific IFN-gamma(+)CD4(+) and IFN-gamma(+)CD8(+) cells in the response of whole blood to mycobacterial challenge. In principal component analysis, the first 3 components explain 78% of the overall variance consistent with the effect of pleiotropic regulatory genes of human antimycobacterial immunity. These results directly demonstrate the pivotal role played by host genetics in quantitative measures of antimycobacterial immunity underlying immune diagnosis of TB infection.