Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection  

作　　者：Cong Peng Fan Jiang Yinping Liu Yong Xue Peng Cheng Jie Wang Liang Wang Wenping Gong 

机构地区：[1]Hebei North University,Zhangjiakou 075000,Hebei Province,China [2]Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment,Senior Department of Tuberculosis,Eighth Medical Center of PLA General Hospital,Beijing 100091,China [3]Department of Geriatrics,Eighth Medical Center of PLA General Hospital,Beijing 100091,China [4]Section of Health,No.94804 Unit of the Chinese People's Liberation Army,Shanghai 200434,China

出　　处：《Infectious Diseases & Immunity》2024年第1期10-24,共15页感染性疾病与免疫（英文）

基　　金：supported by the BeijingMunicipal Science&Technology Commission(7212103);the Eighth Medical Center of PLA General Hospital(MS202211002).

摘　　要：Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection states.Therefore,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests.Methods:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and immunoinformatics.Immune responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays.This study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,China.Blood samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves.Results:A novel MEBDB,designated as CP19128P,was generated.CP19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell epitopes.In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses.CP19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity.Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs(AUC,0.887[0.782-0.993]or 0.984[0.958-1.00

关 键 词：TUBERCULOSIS Latent tuberculosis infection Active tuberculosis Multiepitope-based diagnostic biomarker Bioinformatics:Immunoinformatics 

分 类 号：R52[医药卫生—内科学]