mRNA profiling of cytokines to understand paradoxical response in HIV-uninfected tuberculous meningitis

IF 2.8 3区医学 Q3 IMMUNOLOGY Tuberculosis Pub Date : 2023-12-09 DOI:10.1016/j.tube.2023.102463

Jayantee Kalita , Ruchi Shukla , Prakash C. Pandey , Vivek Singh , Rudrashish Haldar , Usha K. Misra

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Abstract

Paradoxical reaction (PR) in tuberculous meningitis (TBM) is a major management issue. We report mRNA profiling of cytokines to understand PR in HIV-uninfected TBM patients. 72 patients with TBM were included, and their clinical, MRI, and mRNA profiling of tumor necrosis factor (TNF) α, interleukin (IL) 6, IL10 and interferon (IFN) γ genes in the peripheral blood mononuclear cells were done at admission and 6 weeks of antitubercular treatment. Cytokine profiling was done using reverse transcriptase polymerase chain reaction. PR was defined if repeat MRI at 6 weeks revealed new or increase in exudates, tuberculoma, hydrocephalus or infarctions. Outcome was defined at 6 months using modified Rankin Scale (mRS), and categorized as death, poor and good. 44 (61.1 %) patients had PR, and 28 (38.9 %) had paradoxical tuberculoma (PT). The expression of IL6 and TNFα genes were higher in PR and PT groups. Stage of meningitis and hydrocephalus at admission predicted PR. Patients with PR and PT had more frequently poor outcome.

About three-fifth HIV-uninfected TBM patients have PR and two-fifth have PT. Paradoxical reaction is associated with higher expression of IL6 and TNFα. Patients with severe meningitis with hydrocephalus develop PR more frequently.

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通过细胞因子 mRNA 图谱了解未感染艾滋病毒的结核性脑膜炎患者的矛盾反应

结核性脑膜炎（TBM）中的变态反应（PR）是一个重要的管理问题。我们报告了细胞因子的 mRNA 图谱，以了解未感染 HIV 的 TBM 患者的 PR 情况。我们纳入了 72 名 TBM 患者，在入院时和抗结核治疗 6 周后对他们的临床、磁共振成像以及外周血单核细胞中肿瘤坏死因子 (TNF) α、白细胞介素 (IL) 6、IL10 和干扰素 (IFN) γ 基因的 mRNA 图谱进行了分析。细胞因子分析采用逆转录酶聚合酶链反应法进行。如果 6 周后重复磁共振成像发现渗出物、结核瘤、脑积水或梗死新的或增加，则定义为 PR。6 个月后的预后采用改良兰金量表（mRS）进行定义，分为死亡、不良和良好。44例（61.1%）患者患有PR，28例（38.9%）患者患有矛盾性结核瘤（PT）。PR 组和 PT 组的 IL6 和 TNFα 基因表达量较高。入院时脑膜炎和脑积水的分期预示着 PR 的发生。约五分之三的未感染艾滋病毒的 TBM 患者有 PR，五分之二的患者有 PT。副反应与 IL6 和 TNFα 的高表达有关。伴有脑积水的重症脑膜炎患者更常出现 PR。

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来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.