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与HIV感染孕妇潜伏性结核检测不一致相关的定量IFN-γ和IL-2反应

Quantitative IFN-γ and IL-2 Response Associated with Latent Tuberculosis Test Discordance in HIV-infected Pregnant Women.

作者信息

Mathad Jyoti S, Bhosale Ramesh, Balasubramanian Usha, Kanade Savita, Mave Vidya, Suryavanshi Nishi, Gupte Nikhil, Joshi Samir, Chandanwale Ajay, Dupnik Kathryn M, Kulkarni Vandana, Deshpande Prasad, Fitzgerald Daniel W, Gupta Amita

机构信息

1 Center for Global Health, Division of Infectious Diseases, Weill Cornell Medical College, New York, New York.

2 Department of Obstetrics and Gynaecology, Byramjee Jeejeebhoy Government Medical College/Sassoon General Hospital, Pune, India.

出版信息

Am J Respir Crit Care Med. 2016 Jun 15;193(12):1421-8. doi: 10.1164/rccm.201508-1595OC.

DOI:10.1164/rccm.201508-1595OC
PMID:26765255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4910889/
Abstract

RATIONALE

Pregnant women with latent tuberculosis infection (LTBI) are at high risk for development of TB, especially if infected with HIV.

OBJECTIVES

To assess the performance of LTBI tests in pregnant and postpartum women infected with HIV, investigate the immunology behind discordance in pregnancy, and explore the implications for the development of postpartum TB.

METHODS

We screened pregnant women in their second/third trimester and at delivery for LTBI using the tuberculin skin test (TST) and IFN-γ release assay (IGRA) (QuantiFERON Gold). A subset of antepartum women had longitudinal testing, with repeat testing at delivery and postpartum and additional cytokines measured from the IGRA supernatant. The kappa statistic and Wilcoxon rank sum test were used to determine agreement and comparison of cytokine concentrations, respectively.

MEASUREMENTS AND MAIN RESULTS

Of 252 enrolled, 71 (28%) women had a positive IGRA but only 27 (10%) had a positive TST (P < 0.005). There was 75% agreement (kappa, 0.25). When stratified by pregnancy versus delivery, 20% had IGRA(+)/TST(-) discordance at each time point. A positive IGRA was associated with known TB contact (odds ratio, 3.6; confidence interval, 1.2-11.1; P = 0.02). Compared with IGRA(+)/TST(+), women with IGRA(+)/TST(-) discordance had significantly less IFN-γ (1.85 vs. 3.48 IU/ml; P = 0.02) and IL-2 (46.17 vs. 84.03 pg/ml; P = 0.01). Five developed postpartum TB, of which three had IGRA(+)/TST(-) discordance during pregnancy.

CONCLUSIONS

Choice of LTBI test in pregnant women infected with HIV affects results. Pregnant women with IGRA(+)/TST(-) discordance had less IFN-γ and IL-2 than those with concordant-positive results and may represent an especially high-risk subset for the development of active TB postpartum.

摘要

原理

潜伏性结核感染(LTBI)的孕妇发生结核病的风险很高,尤其是感染HIV的孕妇。

目的

评估LTBI检测在感染HIV的孕妇和产后妇女中的表现,研究孕期不一致结果背后的免疫学机制,并探讨其对产后结核病发生的影响。

方法

我们使用结核菌素皮肤试验(TST)和干扰素-γ释放试验(IGRA)(QuantiFERON Gold)对妊娠中晚期和分娩时的孕妇进行LTBI筛查。一部分产前妇女进行了纵向检测,在分娩时和产后重复检测,并从IGRA上清液中检测其他细胞因子。分别使用kappa统计量和Wilcoxon秩和检验来确定一致性和比较细胞因子浓度。

测量指标和主要结果

在252名入组者中,71名(28%)妇女IGRA检测呈阳性,但只有27名(10%)TST检测呈阳性(P < 0.005)。一致性为75%(kappa值为0.25)。按孕期与分娩分层时,每个时间点有20%的妇女存在IGRA(+)/TST(-)不一致情况。IGRA检测呈阳性与已知的结核病接触史相关(比值比,3.6;置信区间,1.2 - 11.1;P = 0.02)。与IGRA(+)/TST(+)的妇女相比,IGRA(+)/TST(-)不一致的妇女的干扰素-γ(1.85对3.48 IU/ml;P = 0.02)和白细胞介素-2(46.17对84.03 pg/ml;P = 0.01)显著减少。5名妇女发生了产后结核病,其中3名在孕期存在IGRA(+)/TST(-)不一致情况。

结论

感染HIV的孕妇中LTBI检测方法的选择会影响结果。IGRA(+)/TST(-)不一致的孕妇比结果一致为阳性的孕妇的干扰素-γ和白细胞介素-2更少,可能是产后发生活动性结核病的特别高危亚组。

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