State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Department of Immunology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
Department of Allergy, Zhongnan Hospital, Wuhan University, Wuhan, China.
Front Cell Infect Microbiol. 2021 Mar 15;11:634915. doi: 10.3389/fcimb.2021.634915. eCollection 2021.
Tuberculosis (TB) is the leading infectious cause of mortality worldwide. However, the diagnosis of TB, especially extrapulmonary TB (EPTB) diagnosis from lesion tissues, remains a challenge. Nucleic acid aptamers are analogous to antibodies and have advantages of easier modification, high specificity, and affinity. Mannose-capped lipoarabinomannan (ManLAM) is a unique surface lipoglycan component or constantly released from ( cell wall, which makes it a perfect candidate biomarker for TB diagnosis. Our present study aims to establish ManLAM aptamer-based immunohistochemistry (IHC) method for TB diagnosis. We performed TB diagnosis using 263 formalin-fixed paraffin-embedded tissue samples including 213 TB samples (pulmonary TB (PTB) and EPTB), and 8 samples from latent TB infection (LTBI) high risk subjects, and 42 samples from other non-TB patients with ManLAM aptamer-based IHC and routine laboratory TB diagnostic methods parallelly. The sensitivity and specificity of the ManLAM aptamer-based IHC were 86.38% and 92.86%, with much higher sensitivity than those of mycobacterial culture (9.66%) and acid-fast staining (AFS) (43.01%) and comparability to Interferon-gamma Release Assay (IGRA) (84.38%) and GeneXpert (79.31%). High agreement between ManLAM based-IHC and IGRA or GeneXpert for TB diagnosis were observed. Furthermore, ManLAM aptamer-based IHC combination with other routine TB laboratory diagnostic methods significantly increased the sensitivity up to 88.64%-97.92%. As our knowledge, this is the first report about aptamer-based IHC for disease diagnosis. Thus, ManLAM aptamer-based IHC has potentials for TB diagnosis, including PTB, and EPTB, and assists the diagnosis of LTBI with high effectiveness, feasibility, and easy production.
结核病（TB）是全球导致死亡的主要传染病原因。然而，结核病的诊断，特别是从病变组织中诊断肺外结核病（EPTB），仍然是一个挑战。核酸适体类似于抗体，具有易于修饰、高特异性和亲和力等优势。甘露糖封端的脂阿拉伯甘露聚糖（ManLAM）是一种独特的表面糖脂成分，或不断从细胞壁释放出来，使其成为结核病诊断的理想候选生物标志物。本研究旨在建立基于甘露糖封端的脂阿拉伯甘露聚糖（ManLAM）适体的免疫组织化学（IHC）方法用于结核病的诊断。我们使用 263 份福尔马林固定石蜡包埋的组织样本进行了结核病诊断，其中包括 213 份结核病样本（肺结核（PTB）和 EPTB），8 份潜伏性结核病感染（LTBI）高危人群样本，以及 42 份来自其他非结核病患者的样本，我们平行地使用 ManLAM 适体的 IHC 和常规实验室结核病诊断方法进行检测。基于 ManLAM 适体的 IHC 的灵敏度和特异性分别为 86.38%和 92.86%，其灵敏度明显高于分枝杆菌培养（9.66%）和抗酸染色（AFS）（43.01%），与干扰素-γ释放分析（IGRA）（84.38%）和 GeneXpert（79.31%）相当。基于 ManLAM 的 IHC 与 IGRA 或 GeneXpert 对结核病诊断的高度一致性。此外，将 ManLAM 适体与其他常规结核病实验室诊断方法相结合，可将灵敏度提高至 88.64%-97.92%。据我们所知，这是首个关于适体用于疾病诊断的报道。因此，基于 ManLAM 适体的 IHC 具有用于结核病诊断的潜力，包括肺结核和肺外结核病，并具有高效、可行和易于生产的优势，可辅助 LTBI 的诊断。
