细胞因子预测JAK抑制剂治疗COVID-19临床疗效的研究

A. A. Novikov, E. N. Aleksandrova, G. E. Bajmakanova, G. V. Lukina, N. A. Bodunova, V. I. Vechorko, O. V. Averkov, S. N. Shcherbo, M. I. Savina, T. I. Turkina, I. E. Khatkov
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引用次数: 0

摘要

Janus激酶抑制剂(JAKi)由于促炎细胞因子水平正常化而具有免疫抑制作用,被用于治疗COVID-19的细胞因子风暴。这一事实使得有必要寻找这种小分子药物功效的预测因子。研究的目的。评价细胞因子预测JAKi在COVID-19患者疗效的可能性。材料和方法。我们检查了86名COVID-19患者:50名男性和36名女性。年龄57,0岁;(50 0 - 65 0)年。PCR证实了SARS-CoV-2的存在。对照组由30名按性别和年龄匹配的健康捐赠者组成。JAKi疗效的标准是恢复、疗效(换用另一种药物)或死亡。ELISA检测血清IL-1β、-6、-8、-17、TNF-α和GM-CSF的浓度使用美国Invitrogen测试系统公司,根据制造商的说明进行估计。结果。在接受巴西替尼(BTC)治疗的COVID-19患者中,与健康个体相比,基础(JAKi开始前)血清IL-6、TNF-α浓度升高;tofacitinib (TFT) - IL-6, ruxilitinib (RLT) - IL-6和TNF-α。在TFT和RLT开始前,血清IL-1β和GM-CSF浓度下降。IL-6和TNF-α的基础浓度与COVID-19的诊断具有统计学上最强的相关性。BTC治疗5天后,与健康供者相比,IL-8水平升高,GM-CSF浓度降低,IL-6浓度略有升高(p <0.05)。IL-17的基础浓度(大于13.9 pg/ml)表明RLT治疗成功的可能性(roc曲线下面积= 0.99;Ap = 99%;Ds = 80%;Op + = 5.0;Op - = 0.2;置信区间:0.9—-1.0)。结论。基础血清细胞因子浓度可预测COVID-19患者JAKi疗效。
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Cytokines in predicting JAK inhibitors clinical efficacy for COVID-19
Janus kinases inhibitors (JAKi) have an immunosuppressive effect due to the normalization of levels of proinflammatory cytokines, are used in the treatment of cytokine storm in COVID-19. This fact makes it necessary to search a predictor of an efficacy of this small-molecules. The aim of the study. To evaluate the possibility of using cytokines in predicting the efficacy of JAKi in COVID-19. Materials and methods. We examined 86 patients with COVID-19: 50 men and 36 women. The age was 57,0; (50,0–65,0) years. The SARS-CoV-2 presence was confirmed by PCR. The control group consisted of 30 healthy donors matched by sex and age. The criterion for the efficacy of JAKi was recovery, in efficacy – switching to another drug, or death. The serum concentration of IL-1β, –6, –8, –17, TNF-α and GM–CSF by ELISA was estimates using Invitrogen test-systems (USA), according to the manufacturer’s instructions. Results. In COVID-19 patients who received baricitinib (BTC), compared with healthy individuals, basal (before JAKi starting) IL-6, TNF-α serum concentrations were increased; tofacitinib (TFT) – IL-6, ruxilitinib (RLT) – IL-6 and TNF-α. A decrease of IL-1β and GM–CSF serum concentration was noted before the start of TFT and RLT. Basal concentrations of IL-6 and TNF-α are most statistically strongly associated with the diagnosis COVID-19. After 5 days of treatment with BTC, there was an increase in IL-8 level compared to the basal, a decrease in the GM–CSF concentration and a slight increase IL-6 concentration relative to healthy donors (p < 0.05 in all cases). Basal concentration of IL-17 (more than 13.9 pg/ml) indicated the possibility of successful RLT treatment (area under the ROC-curve = 0.99; AP = 99 %; DS = 80 %; OP+ = 5.0; OP– = 0.2; CI: 0.9–1.0). Conclusions. Basal serum concentration of cytokines may predict JAKi efficacy in COVID-19 patients.
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