HIV/Hepatitis Unit, Pasteur Institute in Cambodia, Phnom Penh, Cambodia; Université Paris Diderot-Paris 7, Sorbonne Paris-Cité, Paris, France.
Immunology Platform, Pasteur Institute in Cambodia, Phnom Penh, Cambodia.
J Infect. 2017 May;74(5):456-465. doi: 10.1016/j.jinf.2017.01.016. Epub 2017 Feb 9.
Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment.
Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time.
At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)).
None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients.
尽管人类免疫缺陷病毒（HIV）/结核分枝杆菌（TB）合并感染患者中结核相关免疫重建炎症综合征（TB-IRIS）的发生率很高，但目前尚无诊断检测方法。本研究旨在探讨单核/巨噬细胞活化标志物是否可预测 TB-IRIS 的发生，以及其是否受抗结核（TB）治疗的调节。
我们从 127 例初治抗逆转录病毒治疗的 HIV/TB 合并感染成年人的冷冻血浆中获取样本，这些患者均参与了 CAMELIA 试验，其中 36 例发生了 TB-IRIS。在抗 TB 治疗开始（基线）、治疗 8 周后以及 TB-IRIS 时，检测白细胞介素-1 受体拮抗剂（IL-1Ra）、可溶性 CD14（sCD14）和可溶性 CD163 的浓度。
在基线时，TB-IRIS 和非 IRIS 患者的 IL-1Ra 和 sCD14 浓度相似。虽然 TB-IRIS 患者的 sCD163 浓度显著升高，但在多变量分析中，sCD163 浓度与 TB-IRIS 的发生无关。在 TB-IRIS 时，患者表现出更高的 IL-1Ra 浓度（p=0.002）和 sCD14 浓度（p<0.001）。最显著的结果是抗 TB 治疗 8 周后 IL-1Ra 显著降低（中位数降低：-63%（p<0.0001））。
本研究未发现任何测试的生物标志物与 TB-IRIS 的发生有关。然而，重复测量 IL-1Ra 可能有助于 TB-IRIS 的诊断。治疗过程中 IL-1Ra 显著减少表明，IL-1Ra 可能是 HIV 感染患者抗 TB 治疗反应的替代生物标志物。
