神经梅毒患者脑脊液中RARRES2、MACF1和DCN的表达及诊断价值

The expression and diagnostic value of RARRES2,MACF1,and DCN in cerebrospinal fluid of patients with neurosyphilis

目的探讨神经梅毒患者脑脊液(CSF)中的视黄酸受体应答基因2(RARRES2)、微管微丝交联因子1(MACF1)和核心蛋白多糖(DCN)的表达及其对神经梅毒的诊断价值。方法纳入2020年6月至2022年9月期间南京市第二医院收治的64例非神经梅毒的梅毒患者(梅毒组)和78例神经梅毒患者(神经梅毒组)。神经梅毒患者中包括48例早期神经梅毒患者(早期组)和30例晚期神经梅毒患者(晚期组)。神经梅毒患者均给予常规对症治疗及抗生素驱梅治疗。通过qRT-PCR检测各患者治疗前及神经梅毒患者治疗前后的CSF中RARRES2、MACF1和DCN mRNA水平。采用美国国立卫生研究院卒中量表(NIHSS)评估神经梅毒患者治疗前后的神经功能。采用受试者工作特征(ROC)曲线分析各指标对神经梅毒的诊断价值。结果神经梅毒组患者CSF中的RARRES2、MACF1和DCN mRNA水平均高于梅毒组(均P<0.001)。晚期神经梅毒组患者CSF中的RARRES2、MACF1和DCN mRNA水平均高于早期组(均P<0.001)。与治疗前相比,神经梅毒患者治疗后的NIHSS评分以及RARRES2、MACF1和DCN mRNA水平均降低(均P<0.001)。CSF中RARRES2、MACF1和DCN mRNA联合诊断神经梅毒的曲线下面积(AUC)、灵敏度和特异度分别为0.995、100.00%和93.75%,AUC和灵敏度高于单独诊断。结论神经梅毒患者CSF中RARRES2、MACF1和DCN表达升高,并且与疾病严重程度和治疗反应有关,这三种基因可能是诊断神经梅毒的候选生物标志物。

Objective To investigate the expression of retinoic acid receptor responsive gene 2(RARRES2),microtubule microfilament cross-linking factor 1(MACF1),and core protein polysaccharide(DCN)in cerebrospinal fluid(CSF)of patients with neurosyphilis,and their diagnostic value for neurosyphilis.Methods A total of 64 non neurosyphilis syphilis patients(syphilis group)and 78 neurosyphilis patients(neurosyphilis group)admitted to the Second Hospital of Nanjing between June 2020 and September 2022 were included.Among neurosyphilis patients,there were 48 early neurosyphilis patients(early group)and 30 late neurosyphilis patients(late group).Patients with neurosyphilis are treated with routine symptomatic therapy and antibiotic therapy to expel syphilis.The mRNA levels of RARRES2,MACF1,and DCN in CSF of patients with neurosyphilis before and after treatment were detected by quantitative real-time polymerase chain reaction(qRT-PCR).The National Institutes of Health Stroke Scale(NIHSS)was used to evaluate the neurological function of patients with neurosyphilis before and after treatment.The diagnostic value of various indicators for neurosyphilis was analyzed using receiver operating characteristic(ROC)curves.Results The mRNA levels of RARRES2,MACF1,and DCN in CSF of patients with neurosyphilis were higher than those in the syphilis group(all P<0.001).The mRNA levels of RARRES2,MACF1,and DCN in the CSF of patients with advanced neurosyphilis were higher than those in the early group(all P<0.001).Compared with before treatment,the NIHSS score and RARRES2,MACF1,and DCN mRNA levels of neurosyphilis patients decreased after treatment(all P<0.001).The area under the curve(AUC),sensitivity,and specificity of the combined diagnosis of RARRES2,MACF1,and DCN mRNA in CSF for neurosyphilis were 0.995%,100.00%,and 93.75%,respectively.The AUC and sensitivity were higher than those of individual diagnosis.Conclusions The expression of RARRES2,MACF1,and DCN is elevated in CSF of patients with neurosyphilis,and is associated with disease severity and treatment response.These three genes may be candidate biomarkers for diagnosing neurosyphilis.