结核分枝杆菌胸苷酸激酶抗原检测在初发、高危潜伏性结核分枝杆菌感染中的应用。

Mycobacterium tuberculosis thymidylate kinase antigen assays for designating incipient, high-risk latent M.tb infection.

机构信息

Department of Pathology, Unit of Genetics & Genomics, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda.

Department of Immunology &Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, P o Box 7072, Kampala, Uganda.

出版信息

BMC Infect Dis. 2018 Mar 16;18(1):133. doi: 10.1186/s12879-018-3007-y.

DOI:10.1186/s12879-018-3007-y

PMID:29548281

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5857104/

Abstract

BACKGROUND

Precise designation of high risk forms of latent Mycobacterium tuberculosis-M.tb infections (LTBI) is impossible. Delineation of high-risk LTBI can, however, allow for chemoprophylaxis and curtail majority cases of active tuberculosis (ATB). There is epidemiological evidence to support the view that LTBI in context of HIV-1 co-infection is high-risk for progression to ATB relative to LTBI among HIV-ve persons. We recently showed that assays of M.tb thymidylate kinase (TMKmt) antigen and host specific IgG can differentiate ATB from LTBI and or no TB (NTB, or healthy controls). In this study, we aimed to expose the differential levels of TMKmt Ag among HIV+ve co-infected LTBI relative to HIV-ve LTBI as a strategy to advance these assays for designating incipient LTBI.

METHODS

TMKmt host specific IgM and IgG detection Enzyme Immuno-Assays (EIA) were conducted on 40 TB exposed house-hold contacts (22 LTBI vs. 18 no TB (NTB) by QunatiFERON-TB GOLD®); and TMKmt Ag detection EIA done on 82 LTBI (46 HIV+ve vs 36 HIV-ve) and 9 NTB (American donors). Purified recombinant TMKmt protein was used as positive control for the Ag assays.

RESULTS

IgM levels were found to be equally low across QuantiFERON-TB GOLD® prequalified NTB and TB exposed house-hold contacts. Higher TMKmt host specific IgG trends were found among TB house-hold contacts relative to NTB controls. TMKmt Ag levels among HIV+ve LTBI were 0.2676 ± 0.0197 (95% CI: 0.2279 to 0.3073) relative to 0.1069 ± 0.01628 (95% CI: 0.07385 to 0.14) for HIV-ve LTBI (supporting incipient nature of LTBI in context of HIV-1 co-infection). NTB had TMKmt Ag levels of 0.1013 ± 0.02505 (5% CI: 0.0421 to 0.1606) (intimating that some were indeed LTBI).

CONCLUSIONS

TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI.

摘要

背景

精确指定潜伏性结核分枝杆菌-M.tb 感染（LTBI）的高危形式是不可能的。然而，高危 LTBI 的划定可以允许化学预防，并减少大多数活动性肺结核（ATB）病例。有流行病学证据支持这样一种观点，即在 HIV-1 合并感染的情况下，LTBI 向 ATB 进展的风险高于 HIV-ve 人群中的 LTBI。我们最近表明，结核分枝杆菌胸苷酸激酶（TMKmt）抗原和宿主特异性 IgG 的检测可以区分 ATB 与 LTBI 和/或无结核病（NTB，或健康对照）。在这项研究中，我们旨在揭示 HIV+ve 合并感染 LTBI 中 TMKmt Ag 的差异水平，作为推进这些检测指定初期 LTBI 的策略。

方法

对 40 名结核暴露的家庭接触者（22 名 LTBI 与 18 名无结核病（NTB），通过 QuantiFERON-TB GOLD®）进行 TMKmt 宿主特异性 IgM 和 IgG 检测酶免疫分析（EIA）；对 82 名 LTBI（46 名 HIV+ve 与 36 名 HIV-ve）和 9 名 NTB（美国供体）进行 TMKmt Ag 检测 EIA。纯化的重组 TMKmt 蛋白被用作 Ag 检测的阳性对照。

结果

发现 QuantiFERON-TB GOLD®预筛选的 NTB 和结核暴露家庭接触者的 IgM 水平同样较低。与 NTB 对照组相比，TB 家庭接触者中 TMKmt 宿主特异性 IgG 趋势较高。HIV+ve LTBI 中的 TMKmt Ag 水平为 0.2676 ± 0.0197（95%CI：0.2279 至 0.3073），而 HIV-ve LTBI 为 0.1069 ± 0.01628（95%CI：0.07385 至 0.14）（支持 HIV-1 合并感染背景下 LTBI 的初期性质）。NTB 的 TMKmt Ag 水平为 0.1013 ± 0.02505（5%CI：0.0421 至 0.1606）（暗示其中一些确实是 LTBI）。