Reliance on microbiologic methods to diagnose Mycobacterium tuberculosis infection is a suboptimal approach for children due in part to the paucibacillary nature of the disease. A blood-based biomarker assay, such as the mycobacterial-antibody-secreting cell (MASC) assay, could be a major advance for the field of study of pediatric tuberculosis (TB). Children <15 years of age with clinical concern for TB and age-matched children with no concern for TB were enrolled from outpatient clinics in Karachi, Pakistan. MASC, ferritin, and C-reactive protein (CRP) assays were performed, and results were compared among cases and controls, as well as among children with a case definition of "confirmed TB," "probable TB," or "possible TB." MASC responses were significantly higher among children with TB than among controls (0.41 optical density [OD] versus 0.28 OD, respectively, P < 0.001), and the differences were largely driven by the data from children with confirmed TB (P = 0.002). Ferritin and CRP values were significantly higher among those with confirmed TB than among those with the other disease states and controls (P = 0.004 and P = 0.019, respectively). The use of the MASC assay as a blood-based biomarker for TB disease shows some promise among children with microbiologically confirmed disease; however, the performance characteristics for the majority of young children with unconfirmed TB were suboptimal in this cohort.IMPORTANCE Tuberculosis (TB) in children represents a missed opportunity for diagnosis and preventive therapy. The magnitude or burden of disease in children is not fully understood due to our limitations with respect to exploring sensitive diagnostic algorithms. In a setting of TB endemicity in Pakistan, we carried out a proof-of-concept study to evaluate for the first time the performance of B cell analyses by the use of well-defined diagnostic criteria and NIH consensus guidelines as "culture-confirmed," "probable," and "possible" TB groups. In contrast to detection of serum antibody, we focused on mycobacterial-antibody-secreting cell (MASC) detection as a marker of active disease in children with a strong suspicion of TB. Further work exploring a larger panel of inflammatory biomarkers and enrichment of B cells with the objective of increasing the sensitivity of the current MASC assay would lead to the development of a field-friendly assay for timely diagnosis of childhood TB.

中文翻译：

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用于诊断巴基斯坦儿童结核分枝杆菌感染的抗体分泌细胞。

对于儿童而言，依靠微生物学方法来诊断结核分枝杆菌感染是次优的方法，部分原因是该疾病的脓杆菌性质。基于血液的生物标志物测定，例如分枝杆菌抗体分泌细胞（MASC）测定，可能是小儿肺结核（TB）研究领域的重大进展。巴基斯坦卡拉奇的门诊招募了年龄小于15岁的患有结核病的儿童和年龄无关的结核病儿童。进行了MASC，铁蛋白和C反应蛋白（CRP）分析，并比较了病例和对照以及病例定义为“确诊结核病”，“可能结核病”或“可能结核病”的儿童的结果。 ” 结核病儿童的MASC反应明显高于对照组（0。41个光密度[OD]相对于0.28 OD，P <0.001，差异主要是由确诊为结核病的儿童的数据所驱动（P = 0.002）。在确诊为结核病的患者中，铁蛋白和CRP值明显高于其他疾病状态和对照者（分别为P = 0.004和P = 0.019）。MASC分析作为结核病的血液生物标记物的使用显示了在微生物学证实的疾病儿童中的某些前景。但是，该队列中大多数未确诊结核病的幼儿的表现特征欠佳。重要提示儿童结核病（TB）代表了错过诊断和预防治疗的机会。由于我们在探索敏感的诊断算法方面的局限性，因此尚未完全了解儿童疾病的严重程度或负担。在巴基斯坦某地区的结核病流行地区，我们进行了概念验证研究，首次通过使用明确的诊断标准和NIH共识指南（如“文化确认， ““可能”和“可能”结核病组。与血清抗体检测相反，我们将分枝杆菌抗体分泌细胞（MASC）检测作为患有强烈怀疑结核病儿童活动性疾病的标志物。