Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
PLoS One. 2020 Dec 31;15(12):e0244800. doi: 10.1371/journal.pone.0244800. eCollection 2020.
Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV-TB co-infected patients receiving antiretroviral therapy (ART) has been linked to neutrophil activation. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also associated with neutrophil activation. Since ANCAs are reportedly skewed in TB and HIV infections, we investigated plasma levels of 7 ANCAs in TB-IRIS patients.
We retrospectively compared 17 HIV-TB patients who developed TB-IRIS with controls of similar CD4 count, age and gender who did not (HIV+TB+ n = 17), HIV-infected patients without TB (HIV+TB-, n = 17) and 10 HIV-negative (HIV-TB-) controls. Frozen plasma was collected before ART, at 3 and 9 months of ART, and examined by ELISA for levels of 7 ANCAs directed against; Proteinase 3 (PR3), Myeloperoxidase (MPO), Permeability-increasing protein (BPI), Elastase, Cathepsin, Lysozyme, and Lactoferrin.
Compared to HIV+TB+ controls, pre-ART anti-elastase levels were lower in TB-IRIS patients (p = 0.026) and HIV-TB- controls (p = 0.044), whereas other ANCAs did not show significant differences between groups at any time point. A significant decrease over time could be observed in TB-IRIS patients during ART for anti -PR3 (p = 0.027), -lysozyme (p = 0.011), and -lactoferrin (p = 0.019). Conversely, HIV+TB+ controls showed a significant decrease over time for anti -MPO (p = 0.002), -lyzosyme (p = 0.002) and -elastase (p < 0.001).
The lack of elevated anti-elastase levels in TB-IRIS patients as opposed to HIV+TB+ controls correspond to previous findings of lowered immune capacity in patients that will develop TB-IRIS. This may suggest a specific role for anti-elastase, elastase or even matrix-metalloproteinases in TB-IRIS. The precise dynamics of neutrophil activation in HIV-TB merits further investigation and could provide more insight in the early mechanisms leading up to TB-IRIS.
接受抗逆转录病毒疗法 (ART) 的 HIV-TB 合并感染患者中，与结核病相关的免疫重建炎症综合征 (TB-IRIS) 与中性粒细胞活化有关。抗中性粒细胞胞质抗体 (ANCAs) 也与中性粒细胞活化有关。由于 ANCAs 在结核病和 HIV 感染中存在偏倚，我们研究了 TB-IRIS 患者中 7 种 ANCAs 的血浆水平。
我们回顾性比较了 17 例发生 TB-IRIS 的 HIV-TB 患者和具有相似 CD4 计数、年龄和性别的未发生 TB-IRIS 的 HIV-TB 患者（HIV+TB+，n=17）、未发生结核病的 HIV 感染者（HIV+TB-，n=17）和 10 例 HIV 阴性（HIV-TB-）对照。在 ART 前、ART 后 3 个月和 9 个月采集冷冻血浆，通过 ELISA 检测针对 7 种 ANCAs（蛋白酶 3 [PR3]、髓过氧化物酶 [MPO]、通透性增加蛋白 [BPI]、弹性蛋白酶、组织蛋白酶、溶菌酶和乳铁蛋白）的水平。
与 HIV+TB+ 对照组相比，TB-IRIS 患者在 ART 前的抗弹性蛋白酶水平较低（p=0.026），在 HIV-TB-对照组中也较低（p=0.044），而在任何时间点，其他 ANCAs 在组间均无显著差异。在 ART 期间，TB-IRIS 患者的抗-PR3（p=0.027）、抗-溶菌酶（p=0.011）和抗-乳铁蛋白（p=0.019）水平呈显著下降趋势。相反，HIV+TB+ 对照组在 ART 期间，抗-MPO（p=0.002）、抗-溶菌酶（p=0.002）和抗-弹性蛋白酶（p<0.001）水平呈显著下降趋势。
与 HIV+TB+ 对照组相比，TB-IRIS 患者缺乏升高的抗弹性蛋白酶水平，这与之前发现的在将发生 TB-IRIS 的患者中免疫能力降低的结果相对应。这可能表明抗弹性蛋白酶、弹性蛋白酶甚至基质金属蛋白酶在 TB-IRIS 中具有特定作用。HIV-TB 中中性粒细胞活化的精确动力学值得进一步研究，并可能为导致 TB-IRIS 的早期机制提供更多的见解。
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