拉贡麻省理工学院Galit Alter课题组的一项最新研究，开发出不依赖IFN-γ的结核分枝杆菌暴露的免疫标记物。2019年6月，国际知名学术期刊《Nature Medicine》发表了这一成果。

在本研究中，该团队报告了一组乌干达人，他们是结核病患者的家庭接触者。这些个人十分暴露于Mtb但IFN-γ释放试验和的结核菌素皮肤试验测试呈阴性反应,典型的LTBI“抵制”发展。研究表明，“抵制”拥有IgM类型转换IgG抗体反应和非IFN-γ T细胞反应Mtb-特异蛋白质ESAT6 CFP10，有结核分枝杆菌免疫接触的证据。与传统LTBI患者相比，“抵抗者”显示出更强的抗体亲和力和独特的Mtb特异性IgG Fc谱。这些数据揭示了暴露于Mtb的受试者具有独特的适应性免疫特性，支持了对宿主对Mtb暴露反应的扩展定义，并对公共卫生和临床试验设计具有意义。

研究人员表示，暴露于结核分枝杆菌(Mtb)可导致不同的临床结果，包括原发性进展性结核和潜伏性Mtb感染(LTBI)。鉴定Mtb感染使用结核菌素皮肤试验和interferon-γ(IFN-γ)释放试验IGRA,阳性结果预示提早进行化学预防以防止发展为肺结核。

附：英文原文

Title: IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure

Author: Lenette L. Lu, Malisa T. Smith, Krystle K. Q. Yu, Corinne Luedemann, Todd J. Suscovich, Patricia S. Grace, Adam Cain, Wen Han Yu, Tanya R. McKitrick, Douglas Lauffenburger, Richard D. Cummings, Harriet Mayanja-Kizza, Thomas R. Hawn, W. Henry Boom, Catherine M. Stein, Sarah M. Fortune, Chetan Seshadri, Galit Alter

Issue&Volume: Volume 25 Issue 6，June 2019

Abstract: Exposure to Mycobacterium tuberculosis (Mtb) results in heterogeneous clinical outcomes including primary progressive tuberculosis and latent Mtb infection (LTBI). Mtb infection is identified using the tuberculin skin test and interferon-γ (IFN-γ) release assay IGRA, and a positive result may prompt chemoprophylaxis to prevent progression to tuberculosis. In the present study, we report on a cohort of Ugandan individuals who were household contacts of patients with TB. These individuals were highly exposed to Mtb but tested negative by IFN-γ release assay and tuberculin skin test, ‘resisting’ development of classic LTBI. We show that ‘resisters’ possess IgM, class-switched IgG antibody responses and non-IFN-γ T cell responses to the Mtb-specific proteins ESAT6 and CFP10, immunologic evidence of exposure to Mtb. Compared to subjects with classic LTBI, ‘resisters’ display enhanced antibody avidity and distinct Mtb-specific IgG Fc profiles. These data reveal a distinctive adaptive immune profile among Mtb-exposed subjects, supporting an expanded definition of the host response to Mtb exposure, with implications for public health and the design of clinical trials.

DOI: 10.1038/s41591-019-0441-3

Source:https://www.nature.com/articles/s41591-019-0441-3