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) 疾病状态的不同而变化。年龄或性别等临床变量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很好的探索。在这里，我们分析了青少年队列研究中 140 名结核病暴露南非个体的结核分枝杆菌特异性抗体反应。我们确定了进展为活动性结核病的个体与未进展的匹配对照个体的不同反应特征。与进展存在差异相关的多变量抗体评分 (SeroScore) 可在结核病诊断前 2 年识别出进展者，早于通过进展的 RISK6 转录特征实现的进展者。我们在 Grand Challenges 6-74 队列中验证了这些抗体反应特征。与成人相比，青少年以及男性与女性相比，SeroScore 和 RISK6 与结核病进展风险的相关性更好。这表明年龄和性别是与结核病进展相关的抗体反应的重要但未被充分认识的调节因素。