Byramjee-Jeejeebhoy Government Medical College-Johns Hopkins University Clinical Research Site, Pune, India.
Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College, Pune, India.
Front Immunol. 2021 Jan 27;11:587617. doi: 10.3389/fimmu.2020.587617. eCollection 2020.
Recent studies in adults have characterized differences in systemic inflammation between adults with and without latent tuberculosis infection (LTBI+ . LTBI-). Potential differences in systemic inflammation by LTBI status has not been assess in pregnant women.
We conducted a cohort study of 155 LTBI+ and 65 LTBI- pregnant women, stratified by HIV status, attending an antenatal clinic in Pune, India. LTBI status was assessed by interferon gamma release assay. Plasma was used to measure systemic inflammation markers using immunoassays: IFN, CRP, AGP, I-FABP, IFN, IL-1, soluble CD14 (sCD14), sCD163, TNF, IL-6, IL-17a and IL-13. Linear regression models were fit to test the association of LTBI status with each inflammation marker. We also conducted an exploratory analysis using logistic regression to test the association of inflammatory markers with TB progression.
Study population was a median age of 23 (Interquartile range: 21-27), 28% undernourished (mid-upper arm circumference (MUAC) <23 cm), 12% were vegetarian, 10% with gestational diabetes and 32% with HIV. In multivariable models, LTBI+ women had significantly lower levels of third trimester AGP, IL1β, sCD163, IL-6 and IL-17a. Interestingly, in exploratory analysis, LTBI+ TB progressors had significantly higher levels of IL1, IL-6 and IL-13 in multivariable models compared to LTBI+ non-progressors.
Our data shows a distinct systemic immune profile in LTBI+ pregnant women compared to LTBI- women. Data from our exploratory analysis suggest that LTBI+ TB progressors do not have this immune profile, suggesting negative association of this profile with TB progression. If other studies confirm these differences by LTBI status and show a causal relationship with TB progression, this immune profile could identify subsets of LTBI+ pregnant women at high risk for TB progression and who can be targeted for preventative therapy.
最近的成人研究表明，潜伏性结核感染（LTBI+）和非潜伏性结核感染（LTBI-）成人之间的系统性炎症存在差异。尚未评估 LTBI 状态对孕妇系统性炎症的潜在影响。
我们对 155 名 LTBI+和 65 名 LTBI-的孕妇进行了队列研究，这些孕妇根据 HIV 状况在印度浦那的产前诊所进行分层。LTBI 状态通过干扰素 γ释放试验评估。使用免疫测定法测量血浆中的系统性炎症标志物：IFN、CRP、AGP、I-FABP、IFN、IL-1、可溶性 CD14（sCD14）、sCD163、TNF、IL-6、IL-17a 和 IL-13。线性回归模型用于检验 LTBI 状态与每个炎症标志物的相关性。我们还使用逻辑回归进行了探索性分析，以检验炎症标志物与 TB 进展的相关性。
研究人群的中位年龄为 23 岁（四分位间距：21-27 岁），28%的人营养不良（上臂中部周长（MUAC）<23 cm），12%的人是素食主义者，10%的人患有妊娠糖尿病，32%的人感染了 HIV。在多变量模型中，LTBI+ 孕妇在孕晚期的 AGP、IL1β、sCD163、IL-6 和 IL-17a 水平显著较低。有趣的是，在探索性分析中，与 LTBI+非进展者相比，LTBI+TB 进展者的 IL1、IL-6 和 IL-13 水平在多变量模型中显著更高。
与 LTBI-孕妇相比，我们的数据显示 LTBI+ 孕妇具有明显不同的系统性免疫特征。我们的探索性分析数据表明，LTBI+TB 进展者没有这种免疫特征，表明这种特征与 TB 进展呈负相关。如果其他研究通过 LTBI 状态证实这些差异，并表明与 TB 进展存在因果关系，那么这种免疫特征可以识别出 LTBI+孕妇中具有 TB 进展高风险的亚组，并可以对其进行预防性治疗。
