Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Brigham and Women's Hospital, Boston, MA, USA.
Nat Microbiol. 2024 Jun;9(6):1513-1525. doi: 10.1038/s41564-024-01678-x. Epub 2024 Apr 24.
Antibody features vary with tuberculosis (TB) disease state. Whether clinical variables, such as age or sex, influence associations between Mycobacterium tuberculosis-specific antibody responses and disease state is not well explored. Here we profiled Mycobacterium tuberculosis-specific antibody responses in 140 TB-exposed South African individuals from the Adolescent Cohort Study. We identified distinct response features in individuals progressing to active TB from non-progressing, matched controls. A multivariate antibody score differentially associated with progression (SeroScore) identified progressors up to 2 years before TB diagnosis, earlier than that achieved with the RISK6 transcriptional signature of progression. We validated these antibody response features in the Grand Challenges 6-74 cohort. Both the SeroScore and RISK6 correlated better with risk of TB progression in adolescents compared with adults, and in males compared with females. This suggests that age and sex are important, underappreciated modifiers of antibody responses associated with TB progression.
抗体特征随结核病（TB）疾病状态而变化。临床变量（如年龄或性别）是否影响结核分枝杆菌特异性抗体反应与疾病状态之间的关联尚未得到充分探索。在这里，我们对来自青少年队列研究的 140 名南非 TB 暴露个体的结核分枝杆菌特异性抗体反应进行了分析。我们在进展为活动性 TB 的个体和匹配的非进展对照个体中鉴定出了不同的反应特征。一种与进展相关的多变量抗体评分（SeroScore）可以在 TB 诊断前长达 2 年识别出进展者，比 RISK6 转录进展特征更早。我们在 Grand Challenges 6-74 队列中验证了这些抗体反应特征。SeroScore 和 RISK6 与青少年和男性发生 TB 进展的风险相关性均优于成年人和女性。这表明年龄和性别是与 TB 进展相关的抗体反应的重要、被低估的调节因素。
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