Peculiarities of the immune status of patients with multidrug­resistant pulmonary tuberculosis after application of treatment regimens with bedaquiline and linezolid

N. Lapovets, O. Tkach, I. Platonova, L. Lapovets, V. Akimova
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Abstract

Objective — to investigate immuno-metabolic homeostasis in patients with new and recurrent cases of destructive forms of multidrug-resistant pulmonary tuberculosis (MDR-PTB) after treatment with bedaquiline and linezolid. Materials and methods. A clinical and laboratory examination of 175 people with MDR-PTB (89 patients with new cases and 86 patients with recurrent cases of destructive forms of MDR-PTB). The study was performed before and after treatment with bedaquiline and linezolid. The total leukocytes count (L), the leukocyte differential count (leukocyte formula), was determined in all subjects, The content of populations and subpopulations of lymphocytes were calculated using monoclonal antibodies to CD3+, CD4+, CD8+, CD19+, CD23+, CD56+ lymphocytes antigen in the reaction of indirect immunofluorescence. Quantitative determination of serum immunoglobulins was performed by Manchini radial immunodif­fusion in a gel. The level of circulating immune complexes (CIC) was determined by the spectrophoto­metric method by precipitation in polyethylene glycol. Results and discussion. In patients with new cases of destructive forms of MDR-PTB to treatment revealed hypersensitivity reactions of the first and the fourth type. Expressed activation of humoral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB before treatment, there are pronounced hypersensitivity reactions of the fourth type and activation of the humoral and killer parts of the immune system.Patients with new cases of destructive forms of MDR-PTB after application of treatment regimens with bedaquiline and linezolid have hypersensitivity reactions of the first and fourth types. Activation of humo­ral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed a pronounced hypersensitivity reaction of the first type and activation of the killer and humoral parts of the immune system. Conclusions. In patients with new cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency, which is expressed by a decrease in the level of T-lymphocytes (1.7 times relative to normal) and T-helpers (twice below normal). In patients with recurrent cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency with a marked decrease in the level of T-lymphocytes (1.8 times normal) and T-helpers (1.8 times below normal). In patients with new cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed activation of the T-cell immune system due to increased levels of T-suppressors. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed T-cell immunodeficiency due to the reduced content of T-lymphocytes (1.5 times below normal), namely T-helpers (1.9 times lower than normal).
多药耐药肺结核患者应用贝达喹啉和利奈唑胺治疗方案后免疫状态的特点
目的:探讨破坏性多药耐药肺结核(MDR-PTB)新发和复发患者在贝达喹啉和利奈唑胺治疗后的免疫代谢稳态。材料和方法。对175名耐多药肺结核患者进行临床和实验室检查(89名新发病例和86名破坏性耐多药肺结核复发病例)。研究在贝达喹啉和利奈唑胺治疗前后进行。采用间接免疫荧光反应中CD3+、CD4+、CD8+、CD19+、CD23+、CD56+淋巴细胞抗原单克隆抗体计算淋巴细胞群和亚群的含量。采用曼氏放射免疫扩散凝胶法定量测定血清免疫球蛋白。采用聚乙二醇沉淀分光光度法测定循环免疫复合物(CIC)水平。结果和讨论。在耐多药肺结核破坏性新发病例中,治疗显示出第一种和第四种超敏反应。表达激活体液和杀伤部分的免疫检测。在治疗前破坏性耐多药肺结核复发病例中,有明显的第四种超敏反应和免疫系统的体液和杀伤部分的激活。在应用贝达喹啉和利奈唑胺治疗方案后,耐多药-肺结核破坏性新发病例出现第一和第四型超敏反应。检测到体液免疫和杀伤免疫的激活。在应用贝达喹啉和利奈唑胺治疗方案后,破坏性耐多药肺结核复发病例显示出明显的第一类超敏反应和免疫系统杀伤和体液部分的激活。在治疗前出现破坏性耐多药结核新病例的患者中,发现t细胞免疫缺陷,其表现为t淋巴细胞水平下降(相对于正常水平的1.7倍)和t辅助细胞水平下降(低于正常水平的2倍)。破坏性耐多药结核复发患者在治疗前发现t细胞免疫缺陷,t淋巴细胞水平显著下降(正常水平的1.8倍)和t辅助细胞水平显著下降(低于正常水平的1.8倍)。在应用贝达喹啉和利奈唑胺治疗方案后,耐多药-肺结核破坏性新病例显示,由于t抑制因子水平增加,t细胞免疫系统被激活。在使用贝达喹啉和利奈唑胺治疗方案后,破坏性耐多药结核复发病例显示t细胞免疫缺陷,这是由于t淋巴细胞含量降低(低于正常的1.5倍),即t辅助细胞含量降低(低于正常的1.9倍)。
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