南非德班地区接受抗逆转录病毒治疗的人类免疫缺陷病毒感染者中预测结核病复发的血浆细胞因子。
Plasma Cytokine Predictors of Tuberculosis Recurrence in Antiretroviral-Treated Human Immunodeficiency Virus-infected Individuals from Durban, South Africa.
机构信息
Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban.
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
出版信息
Clin Infect Dis. 2017 Sep 1;65(5):819-826. doi: 10.1093/cid/cix357.
BACKGROUND
Immune correlates of tuberculosis (TB) risk in populations infected with human immunodeficiency virus (HIV) remain understudied, despite HIV being associated with a high burden of TB disease. Here we describe plasma cytokine correlates of TB recurrence in a well-characterized cohort of HIV-infected individuals on antiretroviral therapy (ART) with a history of prior TB cure.
METHODS
Study participants were drawn from a prospective cohort study initiated at the conclusion of a randomized clinical trial in which individuals presented with untreated HIV infection and active pulmonary TB. At baseline, ART was initiated, and TB successfully cured. Participants were screened for TB recurrence quarterly for up to 4 years. TB recurrent cases (n = 63) were matched to controls (n = 123) on sex, study arm assignment in the original trial, and month of enrollment with a subset of cases sampled longitudinally at several time-points.
RESULTS
Three cytokines were associated with increased rates of TB recurrence in univariate models: interleukin 6 (IL6) (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.34-5.28, P = .005), IP10 (OR 4.62, 95% CI 1.69-12.65, P = .003), monokine induced by IFN-γ (MIG) (OR 3.11, 95% CI 1.10-8.82, P = .034). Conversely, interferon β (IFNβ) was associated with decreased TB risk (OR 0.34, 95% CI 0.13-0.87, P = .025). Following multivariate analyses adjusting for covariates IL6, interleukin 1β (IL1β), and interleukin 1Rα (IL1Rα) were associated with increased risk and IFNβ with decreased TB risk. Longitudinal analysis showed that levels of many TB-associated markers, including IL6, IP10, sCD14, and interferon γ (IFNγ) are reduced following TB treatment.
CONCLUSION
These data show that TB recurrence, in HIV-infected individuals on ART is predicted by biomarkers of systemic inflammation, many of which are implicated in more rapid HIV disease progression.
CLINICAL TRIALS REGISTRATION
NCT 01539005.
背景
尽管 HIV 与结核病（TB）疾病负担高有关，但在感染 HIV 的人群中，仍缺乏对与结核病风险相关的免疫指标的研究。在此，我们描述了在接受抗逆转录病毒治疗（ART）且曾有结核病治愈史的 HIV 感染者中，与 TB 复发相关的血浆细胞因子标志物。
方法
本研究从一项前瞻性队列研究中选取参与者，该研究始于一项随机临床试验结束时，参与者表现为未经治疗的 HIV 感染和活动性肺结核。基线时开始进行 ART，成功治愈了 TB。在 4 年内每季度对参与者进行 TB 复发筛查。将 63 例 TB 复发病例（n=63）与 123 例对照（n=123）进行匹配，匹配因素包括性别、原始试验中研究臂的分配和入组月份，并且对部分病例进行了多次时间点的纵向采样。
结果
在单变量模型中，有三种细胞因子与 TB 复发率增加相关：白细胞介素 6（IL6）（比值比[OR]2.66，95%置信区间[CI]1.34-5.28，P=0.005）、干扰素诱导蛋白 10（IP10）（OR 4.62，95%CI1.69-12.65，P=0.003）和干扰素-γ诱导的单核细胞趋化因子（MIG）（OR 3.11，95%CI1.10-8.82，P=0.034）。相反，干扰素-β（IFNβ）与 TB 风险降低相关（OR 0.34，95%CI0.13-0.87，P=0.025）。在调整了协变量后，进行多变量分析，发现白细胞介素 6（IL6）、白细胞介素 1β（IL1β）和白细胞介素 1 受体α（IL1Rα）与增加的 TB 风险相关，而 IFNβ与降低的 TB 风险相关。纵向分析显示，许多与 TB 相关的标志物，包括 IL6、IP10、sCD14 和干扰素 γ（IFNγ），在 TB 治疗后水平降低。
结论
这些数据表明，在接受 ART 的 HIV 感染者中，TB 复发可以通过全身性炎症的生物标志物来预测，其中许多标志物与 HIV 疾病进展更快有关。
临床试验注册
NCT 01539005。
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