Table_1_The changes and its significance of peripheral blood NK cells in patients with tuberculous meningitis.DOCX

ObjectiveTuberculous meningitis (TBM) is the most severe form of tuberculosis (TB). The purpose of this study was to explore the relationship between the number of natural killer (NK) cells and adaptive immune status, and disease severity in TBM patients.
MethodsWe conducted a retrospective study on 244 TB patients and 146 healthy control subjects in the 8th Medical Center of the PLA General Hospital from March 2018 and August 2023.
ResultsThe absolute count of NK cells in the peripheral blood of TBM patients was significantly lower than that in normal controls (NC), latent tuberculosis infection (LTBI), and non-severe TB (NSTB) patients (p < 0.05). The proportion of TBM patients (48.7%) with a lower absolute count of NK cells than the normal reference value was significantly higher than that in NC (5.2%) and LTBI groups (4.0%) (p < 0.05), and slightly higher than that in NSTB group (36.0%) (p > 0.05). The absolute counts of lymphocyte subsets in TBM combined with other active TB group, etiology (+) group, IGRA (−) group, and antibody (+) group were lower than that in simple TBM group, etiology (−) group, IGRA (+) group, and antibody (−) group, respectively. The CD3+ T, NK, and B cells in BMRC-stage III TBM patients were significantly lower than those in stage I and stage II patients (p < 0.05). The counts of CD3+ T, CD4+ T, and B cells in the etiology (+) group were significantly lower than those in the etiology (−) group (p < 0.05).
ConclusionThe absolute counts of lymphocyte subsets in the peripheral blood of TBM patients were significantly decreased, especially in NK cells. The reduction of these immune cells was closely related to the disease severity and had a certain correlation with cellular and humoral immune responses. This study helps to better understand the immune mechanism of TBM and provides reliable indicators for evaluating the immune status of TBM patients in clinical practice.

【研究目的】结核性脑膜炎（Tuberculous meningitis, TBM）是最为凶险的结核病（Tuberculosis, TB）临床类型。本研究旨在探讨结核性脑膜炎患者外周血自然杀伤（natural killer, NK）细胞数量与适应性免疫状态及疾病严重程度之间的关联。
【研究方法】本研究为回顾性研究，纳入2018年3月至2023年8月期间于中国人民解放军总医院第八医学中心就诊的244例结核病患者及146名健康对照者。
【研究结果】结核性脑膜炎患者外周血NK细胞绝对计数显著低于正常对照（normal control, NC）组、潜伏结核感染（latent tuberculosis infection, LTBI）组及非重症结核病（non-severe TB, NSTB）患者（P<0.05）。外周血NK细胞绝对计数低于正常参考值的结核性脑膜炎患者占比为48.7%，显著高于NC组（5.2%）与LTBI组（4.0%）（P<0.05），且略高于NSTB组（36.0%），但差异无统计学意义（P>0.05）。合并其他活动性结核的结核性脑膜炎患者组、病原学阳性组、干扰素γ释放试验（Interferon Gamma Release Assay, IGRA）阴性组及抗体阳性组的外周血淋巴细胞亚群绝对计数，分别低于单纯结核性脑膜炎组、病原学阴性组、IGRA阳性组及抗体阴性组。英国医学研究理事会（British Medical Research Council, BMRC）分期为Ⅲ期的结核性脑膜炎患者，其外周血CD3+T细胞、NK细胞及B细胞计数均显著低于Ⅰ期与Ⅱ期患者（P<0.05）。病原学阳性组的CD3+T细胞、CD4+T细胞及B细胞计数均显著低于病原学阴性组（P<0.05）。
【研究结论】结核性脑膜炎患者外周血淋巴细胞亚群绝对计数均显著降低，其中NK细胞减少尤为明显。上述免疫细胞的数量减少与疾病严重程度密切相关，且与细胞免疫及体液免疫应答存在一定关联。本研究有助于更深入地阐明结核性脑膜炎的免疫发病机制，同时可为临床评估结核性脑膜炎患者的免疫状态提供可靠的参考指标。