Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis.
Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis.
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DOI：
10.1371/journal.pone.0274415
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Boyle, David S.
中科院分区：
文献类型：
--
作者：
Cantera, Jason L.;Lillis, Lorraine M.;Peck, Roger B.;Moreau, Emmanuel;Schouten, James A.;Davis, Paul;Drain, Paul K.;Andama, Alfred;Pinter, Abraham;Kawasaki, Masanori;Kallenius, Gunilla;Sundling, Christopher;Dobos, Karen M.;Flores, Danara;Chatterjee, Delphi;Murphy, Eileen;Halas, Olivia R.;Boyle, David S.
阿拉伯脂甘露聚糖 (LAM) 是结核分枝杆菌 (MTB) 细胞壁的一种成分，可在感染 MTB 的活动性结核病 (TB) 患者的尿液中检测到。 LAM 特异性抗体 (Igs) 已通过多种传统和重组方法开发出来，可用于快速诊断测试 (RDT)。我们评估了 TB LAM Igs 的分析性能，以确定性能优于现有尿液 LAM 检测的配对。我们使用基于电化学发光的多重液体免疫测定法以矩阵形式评估了 25 种新的 Ig 和 4 种现有的 Ig。总共 841 配对 Ig 组合受到来自代表不同系统发育谱系的 MTB 菌株的体外培养 LAM (cLAM) 以及来自活动性肺结核成人尿液的尿液 LAM (uLAM) 的攻击。使用 MTB Aoyama-B cLAM 确定下调 Ig 对的分析灵敏度，同时使用临床样本确定诊断准确性。测试 cLAM 时，MTB 谱系 1-4 中 Ig 对的反应性相似，但谱系 5:6 的 Ig 对之间的反应性明显更高。总体而言，与S4-20/A194-01的参考对相比，41对Ig对cLAM具有强结合亲和力，其中28对Ig对cLAM和uLAM均表现出强亲和力。对临床尿液样本的回顾性检测显示出不同的敏感性（12-80%）和特异性（14-100%）。前五对与参考对具有相似的分析检测限，但在四种情况下，临床 uLAM 样本的灵敏度和特异性较差。总体而言，uLAM 呈现的表位与 cLAM 不同，这可能会影响在患者样本中测试 uLAM 时的抗体性能。几个新的 Ig 对对 cLAM 具有相似的高敏感性范围，但总体而言，在本轮筛选中没有发现新的候选 Ig 对与现有的最佳对相比，uLAM 的性能有所提高。
Lipoarabinomannan (LAM), a component of the Mycobacterium tuberculosis (MTB) cell wall, is detectable in the urine of MTB infected patients with active tuberculosis (TB). LAM-specific antibodies (Igs) have been developed by a variety of traditional and recombinant methods for potential use in a rapid diagnostic test (RDT). We evaluated the analytical performance of the TB LAM Igs to identify pairs that offer superior performance over existing urine LAM tests. We assessed 25 new and 4 existing Igs in a matrixed format using a multiplex electrochemiluminescence-based liquid immunoassay. A total of 841 paired Ig combinations were challenged with in vitro cultured LAM (cLAM) derived from MTB strains representing diverse phylogenetic lineages, alongside urinary LAM (uLAM) from the urine of adults with active pulmonary TB. Analytical sensitivity of down-selected Ig pairs was determined using MTB Aoyama-B cLAM, while diagnostic accuracy was determined using clinical samples. When testing cLAM, the reactivity of Ig pairs was similar across MTB lineages 1–4 but lineage 5:6 had significantly more reactivity among Ig pairs. Overall, 41 Ig pairs had a strong binding affinity to cLAM, as compared to the reference pair of S4-20/A194-01, and 28 Ig pairs therein exhibited a strong affinity for both cLAM and uLAM. Retrospective testing on clinical urine specimens demonstrated varying sensitivities (12–80%) and specificities (14–100%). The five top pairs had a similar analytical limit of detection to the reference pair but in four instances, the sensitivity and specificity with clinical uLAM samples was poor. Overall, epitopes presented by uLAM are different from cLAM, which may affect antibody performance when testing uLAM in patient samples. Several new Ig pairs had similar ranges of high sensitivity to cLAM but overall, there were no new candidate Ig pairs identified in this round of screening with increased performance with uLAM as compared to an existing optimal pair.
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影响因子：
2.2
作者：
Hamasur, B;Bruchfeld, J;Svenson, SB
通讯作者：
Svenson, SB
DOI：
10.1016/j.jbc.2021.101265
发表时间：
2021-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
De P;Amin AG;Flores D;Simpson A;Dobos K;Chatterjee D
通讯作者：
Chatterjee D
影响因子：
3.7
作者：
Hamasur B;Bruchfeld J;van Helden P;Källenius G;Svenson S
通讯作者：
Svenson S
影响因子：
3.7
作者：
Broger, Tobias;Tsionksy, Michael;Sigal, George B.
通讯作者：
Sigal, George B.
影响因子：
4.6
作者：
Magni, Ruben;Rruga, Fatlum;Luchini, Alessandra
通讯作者：
Luchini, Alessandra