Detection of Mycobacterium tuberculosis complex DNA in CD34-positive peripheral blood mononuclear cells of asymptomatic tuberculosis contacts: an observational study.
Detection of Mycobacterium tuberculosis complex DNA in CD34-positive peripheral blood mononuclear cells of asymptomatic tuberculosis contacts: an observational study.
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在无症状的结核病接触的CD34阳性外周血单核细胞中检测结核分枝杆菌复合物DNA：一项观察性研究。
DOI：
10.1016/s2666-5247(21)00043-4
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
Martineau AR
中科院分区：
文献类型：
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作者：
Belay M;Tulu B;Younis S;Jolliffe DA;Tayachew D;Manwandu H;Abozen T;Tirfie EA;Tegegn M;Zewude A;Forrest S;Mayito J;Huggett JF;Jones GM;O'Sullivan DM;Martineau HM;Noursadeghi M;Chandran A;Harris KA;Nikolayevskyy V;Demaret J;Berg S;Vordermeier M;Balcha TT;Aseffa A;Ameni G;Abebe M;Reece ST;Martineau AR
表达 CD34 表面标记的造血干细胞已被认为是潜伏结核感染期间结核分枝杆菌复合菌的生态位。我们的目的是确定从生活在结核病高负担环境中的无症状成年人中分离出的 CD34 阳性外周血单核细胞 (PBMC) 中是否可以检测到结核分枝杆菌复合体 DNA。我们于 2017 年 11 月 22 日至 2019 年 1 月 10 日在埃塞俄比亚进行了一项横断面研究。使用数字 PCR (dPCR) 来确定从无症状 HIV 感染者或近期家庭或职业接触人类或牛结核病指示病例的无症状成人的 100 mL 血液中分离出的 PBMC 中是否可检测到结核分枝杆菌复合体 DNA。参与者是从亚的斯亚贝巴及其周边地区的艾滋病毒诊所、结核病诊所和养牛场招募的。在 HIV 感染者的子集中进行了一项巢式前瞻性研究，以评估异烟肼预防性治疗是否能有效清除 PBMC 中的结核分枝杆菌复合体 DNA。随访时间为 2018 年 7 月 20 日至 2019 年 2 月 13 日。还对所有基线和随访样本进行了 QuantiFERON-TB Gold 检测。为横断面分析提供数据的 284 名参与者中的 197 名 (70%) 提供了配对 CD34 阳性和 CD34 阴性 PBMC 分数的有效 dPCR 数据（即每孔液滴计数 >10 000）。在 197 名具有有效 dPCR 数据的参与者中，156 名的 PBMC 中检测到结核分枝杆菌复合体 DNA（79%，95% CI 74-85）。它在 CD34 阳性部分中比在 CD34 阴性部分中更常见（197 人中的 154 人 [73%] vs 197 人中的 46 人 [23%]；p<0·0001）。 dPCR 检测到的结核分枝杆菌复合体 DNA 的患病率在 QuantiFERON 阴性和 QuantiFERON 阳性参与者之间没有差异（99 人中的 77 人 [78%] 与 98 人中的 79 人 [81%]；p=0·73），但 HIV 感染者中的患病率高于未感染 HIV 的参与者（75 人中的 67 人 [89%] 比 98 人中的 89 人 [73%]） 122，p=0·0065）。相比之下，感染 HIV 的 QuantiFERON 阳性参与者的比例低于未感染 HIV 的参与者（75 人中的 25 人 [33%] vs 122 人中的 73 人 [60%]；p<0·0001）。异烟肼预防性治疗将 dPCR 检测到的结核分枝杆菌复合体 DNA 的患病率从基线时的 43 名 HIV 感染者中的 41 例 (95%) 降低到治疗后的 43 例中的 23 例 (53%) (p<0·0001)，但它并不影响 QuantiFERON 阳性的患病率（基线时 43 例中的 17 例 [40%]，治疗后为 43 例中的 13 例 [30%]； p=0·13）。我们报告了一种潜伏性结核感染的新型分子微生物生物标志物，其特性与商业干扰素-γ释放测定的特性不同。我们的研究结果表明，骨髓是潜伏感染个体中结核分枝杆菌的生存环境。 PBMC 中结核分枝杆菌复合体 DNA 的检测在诊断潜伏性结核感染、监测预防性治疗反应以及作为预防或治疗潜伏性结核感染干预措施临床试验的结果测量方面具有潜在应用。英国医学研究委员会。
Haematopoietic stem cells expressing the CD34 surface marker have been posited as a niche for Mycobacterium tuberculosis complex bacilli during latent tuberculosis infection. Our aim was to determine whether M tuberculosis complex DNA is detectable in CD34-positive peripheral blood mononuclear cells (PBMCs) isolated from asymptomatic adults living in a setting with a high tuberculosis burden. We did a cross-sectional study in Ethiopia between Nov 22, 2017, and Jan 10, 2019. Digital PCR (dPCR) was used to determine whether M tuberculosis complex DNA was detectable in PBMCs isolated from 100 mL blood taken from asymptomatic adults with HIV infection or a history of recent household or occupational exposure to an index case of human or bovine tuberculosis. Participants were recruited from HIV clinics, tuberculosis clinics, and cattle farms in and around Addis Ababa. A nested prospective study was done in a subset of HIV-infected individuals to evaluate whether administration of isoniazid preventive therapy was effective in clearing M tuberculosis complex DNA from PBMCs. Follow-up was done between July 20, 2018, and Feb 13, 2019. QuantiFERON-TB Gold assays were also done on all baseline and follow-up samples. Valid dPCR data (ie, droplet counts >10 000 per well) were available for paired CD34-positive and CD34-negative PBMC fractions from 197 (70%) of 284 participants who contributed data to cross-sectional analyses. M tuberculosis complex DNA was detected in PBMCs of 156 of 197 participants with valid dPCR data (79%, 95% CI 74–85). It was more commonly present in CD34-positive than in CD34-negative fractions (154 [73%] of 197 vs 46 [23%] of 197; p<0·0001). Prevalence of dPCR-detected M tuberculosis complex DNA did not differ between QuantiFERON-negative and QuantiFERON-positive participants (77 [78%] of 99 vs 79 [81%] of 98; p=0·73), but it was higher in HIV-infected than in HIV-uninfected participants (67 [89%] of 75 vs 89 [73%] of 122, p=0·0065). By contrast, the proportion of QuantiFERON-positive participants was lower in HIV-infected than in HIV-uninfected participants (25 [33%] of 75 vs 73 [60%] of 122; p<0·0001). Administration of isoniazid preventive therapy reduced the prevalence of dPCR-detected M tuberculosis complex DNA from 41 (95%) of 43 HIV-infected individuals at baseline to 23 (53%) of 43 after treatment (p<0·0001), but it did not affect the prevalence of QuantiFERON positivity (17 [40%] of 43 at baseline vs 13 [30%] of 43 after treatment; p=0·13). We report a novel molecular microbiological biomarker of latent tuberculosis infection with properties that are distinct from those of a commercial interferon-γ release assay. Our findings implicate the bone marrow as a niche for M tuberculosis in latently infected individuals. Detection of M tuberculosis complex DNA in PBMCs has potential applications in the diagnosis of latent tuberculosis infection, in monitoring response to preventive therapy, and as an outcome measure in clinical trials of interventions to prevent or treat latent tuberculosis infection. UK Medical Research Council.