结核性脑膜炎患者血清神经细胞黏附分子1与转甲状腺素蛋白的表达及临床意义研究

Expression Levels and Clinical Significance of Serum NCAM1 and TTR in Tuberculous Meningitis

背景结核性脑膜炎(TBM)是结核病最严重的类型,通常会导致高死亡率。脑脊液病原学诊断是TBM实验诊断的金标准,但培养时间长(42 d)、培养成本高,容易导致患者病情被延误。目前非侵入性监测技术展现出较广的应用前景,探讨与其相关的指标有助于指导临床治疗。目的探讨TBM患者血清神经细胞黏附分子1(NCAM1)、转甲状腺素蛋白(TTR)的表达,分析其与TBM病情和预后的关系。方法选择2017年3月至2020年12月三亚市人民医院和三亚市中心医院收治的114例TBM患者为TBM组,根据英国医学研究理事会(MRC)分期标准分为Ⅰ期31例、Ⅱ期45例、Ⅲ期38例,TBM患者入组后均接受抗结核治疗,治疗结束后随访1年,根据改良Rankin量表将患者分为预后良好(0~2分,63例)和预后不良(≥3分,51例)。另选择同期46例健康志愿者为对照组。检测TBM组不同时间点血清NCAM1、TTR水平及对照组基线NCAM1、TTR水平,分析其与TBM预后的关系以及对TBM患者预后的预测价值。结果TBM组基线血清NCAM1、TTR水平均低于对照组(P<0.05),Ⅲ期TBM患者基线血清NCAM1、TTR水平低于Ⅱ期TBM患者和Ⅰ期TBM患者(P<0.05)。预后不良TBM患者基线、入院7 d、入院14 d、随访1个月、随访6个月、随访12个月血清NCAM1、TTR水平均低于预后良好TBM患者(P<0.05)。MRC分期Ⅲ期是TBM患者预后不良的危险因素(P<0.05),基线高水平NCAM1、TTR是TBM患者预后不良的保护因素(P<0.05)。基线NCAM1、TTR预测TBM患者预后不良的受试者工作特征(ROC)曲线下面积为0.665、0.689,联合指标(基线NCAM1+基线TTR)预测的ROC曲线下面积为0.879,高于单独基线NCAM1、TTR的ROC曲线下面积(Z=4.428、3.941,P<0.05)。结论TBM患者血清NCAM1、TTR水平均降低,且与TBM病情和预后不良有关,MRC分期Ⅲ期是TBM患者预后不良的危险因素。

Background Tuberculous meningitis(TBM)is the most serious type of tuberculosis,usually yielding a high mortality.Antigen detection test in cerebrospinal fluid is the gold standard for etiological diagnosis of TBM,but it may easily lead to delayed treatment due to long culture time(42 days)and high cost.Non-invasive monitoring technologies have demonstrated a wide application prospect,and exploring relevant indicators will help to guide clinical treatment.Objective To investigate the expression levels of serum neural cell adhesion molecule 1(NCAM1)and transthyretin(TTR),and their associations with the condition and prognosis of TBM patients.Methods A total of 114 TBM patients〔TBM group,including 31 stageⅠ,45 stageⅡ,and 38 stageⅢby the British Medical Research Council(BMRC)staging system〕were recruited from Sanya People's Hospital and Sanya Central Hospital from March 2017 to December 2020.All of them were treated with anti-tuberculosis therapy and followed up for 1 year after treatment,and their prognosis were classified as good(0-2 points,63 cases)and poor(≥3 points,51 cases)by the Modified Rankin Scale.TBM patients were compared to 46 healthy physical examines selected from the two hospitals during the same period in terms of baseline serum NCAM1 and TTR levels.NCAM1 and TTR levels measured at 6 time points(baseline,7,14 days after admission,and 1,6 and 12 months after follow-up)were analyzed,and their associations with as well as predictive values for prognosis in TBM patients were assessed.Results TBM patients had much lower baseline serum NCAM1 and TTR levels than the controls(P<0.05).SageⅢTBM patients had notably lower baseline serum NCAM1 and TTR levels than stageⅠandⅡTBM patients(P<0.05).TBM patients with poor prognosis had significantly lower serum NCAM1 and TTR levels(measured at each of the aforementioned six time points)than those with good prognosis(P<0.05).BMRC stageⅢwas associated with increased risk of poor prognosis(P<0.05),while higher baseline levels of serum NCAM1 and TTR were associated with decreased risk of poor prognosis in TBM patients(P<0.05).For predicting poor prognosis in TBM,the area under the ROC curve of the combination of baseline NCAM1 and TTR was greater than that of baseline NCAM1(0.879 vs 0.665)or baseline TTR(0.879 vs 0.689)alone(Z=4.428,3.941,P<0.05).Conclusion TBM patients were found with decreased serum NCAM1 and TTR levels,which may be associated with their condition and prognosis.BMRC stageⅢmay be a risk factor for poor prognosis in TBM.