Disease extent and anti-tubercular treatment response correlates with Mycobacterium tuberculosis-specific CD4 T-cell phenotype regardless of HIV-1 status.
Disease extent and anti-tubercular treatment response correlates with Mycobacterium tuberculosis-specific CD4 T-cell phenotype regardless of HIV-1 status.
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DOI：
10.1002/cti2.1176
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发表时间：
2020
影响因子：
5.8
通讯作者：
Wilkinson RJ
中科院分区：
文献类型：
--
作者：
Riou C;Du Bruyn E;Ruzive S;Goliath RT;Lindestam Arlehamn CS;Sette A;Sher A;Barber DL;Wilkinson RJ
发展用于结核病诊断和治疗监测的非痰液检测是一个关键的优先事项。最近的数据表明，基于全血的评估结核分枝杆菌（Mtb）特异性CD4 T细胞表型的方法有望实现这一目的，但需要在特征明确的结核病队列中进一步研究。在这项研究中，我们研究了Mtb特异性CD4反应的表型特征、结核病程度和治疗反应之间的关系。使用流式细胞术，我们测量了161名不同TB和HIV状态的参与者全血中Mtb特异性CD4 T细胞表型和功能标志物（HLA‐DR、CD27、CD153、KLRG1、IL‐2、MIP‐1β、TNF‐α和IFN‐γ）的表达。使用xperct值、C反应蛋白、Timika x线评分和单核细胞/淋巴细胞比率对结核病程度进行连续分级。结核分枝杆菌特异性CD4 T细胞抗结核前治疗（ATT）的表型谱与疾病程度密切相关，与HIV状态无关。ATT与Mtb特异性CD4 T细胞表型的主要变化相关，HLA - DR表达降低，CD27和CD153表达增加。主成分分析显示潜伏性结核感染（LTBI）和活动性结核感染（aTB）在ATT前组之间几乎完全分离，而aTB在ATT后组的特征与LTBI组重叠。然而，在治疗失败或复发的患者中，在治疗前和治疗后，Mtb特异性CD4 T细胞表型没有明显变化。基于全血的结核分枝杆菌特异性CD4 T细胞活化和成熟标记物检测可作为结核病疾病程度和治疗监测的非痰基础生物标记物，无论HIV - 1状态如何。更好地了解宿主免疫反应、结核病严重程度和治疗结果之间的关系是开发新型结核病诊断和治疗监测工具的关键。在这项研究中，我们定义了结核患者中结核分枝杆菌特异性IFNγ+ CD4 T细胞反应的概况，分析了其在完成标准抗结核治疗方案后的演变，并评估了宿主CD4反应与临床结核程度和治疗反应的关系。
The development of non‐sputum‐based assays for tuberculosis (TB) diagnosis and treatment monitoring is a key priority. Recent data indicate that whole blood‐based assays to assess the phenotype of Mycobacterium tuberculosis (Mtb)‐specific CD4 T cells hold promise for this purpose and require further investigation in well‐characterised TB cohorts. In this study, we investigated the relationship between the phenotypic signature of Mtb‐specific CD4 responses, TB disease extent and treatment response. Using flow cytometry, we measured the expression of phenotypic and functional markers (HLA‐DR, CD27, CD153, KLRG1, IL‐2, MIP‐1β, TNF‐α and IFN‐γ) on Mtb‐specific CD4 T‐cells in whole blood from 161 participants of varying TB and HIV status. TB disease extent was graded as a continuum using the Xpertct value, C‐reactive protein, Timika radiographic score and monocyte/lymphocyte ratio. The phenotypic profile of Mtb‐specific CD4 T cells pre‐anti‐tubercular treatment (ATT) strongly correlated with disease extent, irrespective of HIV status. ATT associated with major changes in the phenotype of Mtb‐specific CD4 T cells, with decreased expression of HLA‐DR and increased CD27 and CD153 expression. Principal component analysis showed an almost complete separation between latent TB infection (LTBI) and active TB (aTB) pre‐ATT groups, whereas the profile of the aTB post‐ATT group overlapped with the LTBI group. However, in patients experiencing treatment failure or relapse, no significant changes were observed in Mtb‐specific CD4 T‐cell phenotype pre‐ and post‐ATT. Whole blood‐based assays of Mtb‐specific CD4 T‐cell activation and maturation markers can be used as non‐sputum‐based biomarkers of disease extent and treatment monitoring in TB, regardless of HIV‐1 status. A better understanding of the relationship between host immune responses, tuberculosis (TB) disease severity and treatment outcome is key to the development of novel TB diagnostic and treatment monitoring tools. In this study, we defined the profile of Mycobacterium tuberculosis‐specific IFNγ+ CD4 T‐cell response in TB patients, analysed its evolution after completion of a standard anti‐tubercular treatment regimen and evaluated how the host CD4 response associates with clinical TB extent and treatment response.
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影响因子：
3.1
作者：
Di Perri, Giovanni;Aguilar Marucco, Diego;Bonora, Stefano
通讯作者：
Bonora, Stefano
DOI：
10.4049/jimmunol.1101122
发表时间：
2011-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Day CL;Abrahams DA;Lerumo L;Janse van Rensburg E;Stone L;O'rie T;Pienaar B;de Kock M;Kaplan G;Mahomed H;Dheda K;Hanekom WA
通讯作者：
Hanekom WA
影响因子：
82.9
作者：
Malherbe, Stephanus T.;Shenai, Shubhada;Walzl, Gerhard
通讯作者：
Walzl, Gerhard
影响因子：
6.7
作者：
Lindestam Arlehamn CS;McKinney DM;Carpenter C;Paul S;Rozot V;Makgotlho E;Gregg Y;van Rooyen M;Ernst JD;Hatherill M;Hanekom WA;Peters B;Scriba TJ;Sette A
通讯作者：
Sette A
影响因子：
9.4
作者：
Denkinger, Claudia M.;Pai, Madhukar;Menzies, Dick
通讯作者：
Menzies, Dick