Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes
Lipoarabinomannan antigenic epitope differences in tuberculosis disease subtypes
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DOI：
10.1038/s41598-020-70669-9
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发表时间：
2020-08-18
影响因子：
4.6
通讯作者：
Luchini, Alessandra
中科院分区：
文献类型：
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作者：
Magni, Ruben;Rruga, Fatlum;Luchini, Alessandra
对不同的活动性结核病人群进行准确的尿液检测可能会对预防结核病死亡产生革命性的影响。尿脂阿拉伯甘露聚糖 (LAM) 检测以前仅限于 HIV 合并感染的结核病患者。在这项研究中，我们评估了 HIV 阴性、儿童和成人、肺结核和肺外结核患者的尿 LAM。我们使用三种单克隆抗体 MoAb1、CS35 和 A194（可识别不同的 LAM 表位）、单侧免疫测定和盲法队列，对来自秘鲁、几内亚比绍、委内瑞拉、乌干达和美国的 430 名经过微生物学证实的治疗前结核病患者和对照进行了测量。我们评估了检测变异性和合并症（艾滋病毒和糖尿病）的来源。所有抗体都成功区分了结核病阳性患者和结核病阴性患者。三种抗体反应的平均值的 ROAUC 为 0.90； 95% CI 0.87-0.93，90% 敏感性，73.5% 特异性 (80 pg/mL)。 MoAb1 识别 5-甲硫基呋喃糖 (MTX)-甘露糖 (Man) 帽表位，表现最佳，受糖尿影响较小，并以高精度识别培养阳性儿科 (N = 19) 和肺外 (N = 24) 患者（ROAUC 0.87，95% CI 0.77-0.98，0.90 灵敏度 0.80 特异性） 80 pg/mL；ROAUC = 0.96，95% CI 0.92-0.99，82 pg/mL 时灵敏度分别为 96%，特异性为 80%）。 MoAb1 抗体，
An accurate urine test for diverse populations with active tuberculosis could be transformative for preventing TB deaths. Urinary liporabinomannan (LAM) testing has been previously restricted to HIV co-infected TB patients. In this study we evaluate urinary LAM in HIV negative, pediatric and adult, pulmonary and extrapulmonary tuberculosis patients. We measured 430 microbiologically confirmed pretreatment tuberculosis patients and controls from Peru, Guinea Bissau, Venezuela, Uganda and the United States using three monoclonal antibodies, MoAb1, CS35, and A194, which recognize distinct LAM epitopes, a one-sided immunoassay, and blinded cohorts. We evaluated sources of assay variability and comorbidities (HIV and diabetes). All antibodies successfully discriminated TB positive from TB negative patients. ROAUC from the average of three antibodies' responses was 0.90; 95% CI 0.87-0.93, 90% sensitivity, 73.5% specificity (80 pg/mL). MoAb1, recognizing the 5-methylthio-dxylofuranose(MTX)-mannose(Man) cap epitope, performed the best, was less influenced by glycosuria and identified culture positive pediatric (N = 19) and extrapulmonary (N = 24) patients with high accuracy ( ROAUC 0.87, 95% CI 0.77-0.98, 0.90 sensitivity 0.80 specificity at 80 pg/mL; ROAUC = 0.96, 95% CI 0.92-0.99, 96% sensitivity, 80% specificity at 82 pg/mL, respectively). The MoAb1 antibody,