血清纤维连接蛋白联合梅毒非特异性抗体检测在梅毒血清固定患者中排除无症状神经梅毒的初步探讨

Application of serum fibronectin in combination with non-treponemal antibody testing in the exclusion of asymptomatic neurosyphilis among serofast syphilis patients:a preliminary study

目的探讨外周血血清纤维连接蛋白和梅毒非特异性抗体预测无症状神经梅毒的应用价值。方法回顾分析2019年2月至2022年10月苏州大学院附属传染病医院因梅毒血清固定收治入院患者74例,依据2020版梅毒感染诊疗指南,将上述患者分成无症状神经梅毒组(17例)和非神经梅毒组(57例)。分析血清纤维连接蛋白水平和梅毒甲苯胺红不加热血清试验(TRUST)非特异性抗体滴度在两组中的差异。偏态分布资料以M(Q1,Q3)表示,绘制受试者操作特征曲线(ROC曲线),建立二元logistic回归模型。结果非神经梅毒组男25例,女32例,年龄22~76岁;无症状神经梅毒组男10例,女7例,年龄26~66岁。两组患者性别及年龄结构差异均无统计学意义(P>0.05)。无症状神经梅毒组血清纤维连接蛋白水平[486.0(387.5,605.0)mg/L]及血清非特异性抗体滴度水平[以2为底数进行对数转换(-log2滴度),5(4,6)]均高于非神经梅毒组[410.0(347.5,474.5)mg/L、3(1,4)],差异有统计学意义(Z=2.36、4.43,均P<0.05)。血清纤维连接蛋白、梅毒非特异性抗体滴度及二者联合诊断无症状神经梅毒患者的ROC曲线下面积分别为0.689(95%CI:0.540~0.838)、0.850(95%CI:0.757~0.942)、0.878(95%CI:0.787~0.970)。二元Logistic回归分析显示,血清纤维连接蛋白和梅毒非特异性抗体检测结果与血清固定患者中发生无症状神经梅毒具有关联性(P<0.05)。基于二元Logistic回归获得模型方程:Logit(P)=0.008×血清纤维连接蛋白水平+0.090×血清梅毒非特异性抗体滴度倒数-6.483,Logit(P)≥-0.703时提示无症状神经梅毒的可能性大。选取敏感度为100%、特异性最高的点,得出Logit(P)≤-2.863时患者为无症状神经梅毒的可能性为0,按新模型重新分组,19例(25.68%)血清固定患者预测排除无症状神经梅毒。结论血清纤维连接蛋白联合梅毒非特异性抗体检测在梅毒血清固定患者中具有一定的诊断价值,可预测排除部分血清固定的无症状神经梅毒患者。

Objective To evaluate the application value of peripheral blood serum fibronectin in combination with non-treponemal antibody testing in predicting asymptomatic neurosyphilis.Methods A retrospective analysis was conducted on 74 syphilis inpatients in the serofast state at the Affiliated Infectious Diseases Hospital of Soochow University from February 2019 to October 2022.According to the guidelines for the diagnosis and treatment of syphilis(2020 version),the patients were divided into an asymptomatic neurosyphilis group(17 cases)and a non-neurosyphilis group(57 cases).The differences in serum fibronectin levels and non-specific antibody titers detected by the toluidine red unheated serum test(TRUST)were analyzed between the two groups.Skewed data were presented as M(Q1,Q3),and receiver operating characteristic(ROC)curves were plotted to establish a binary logistic regression model.Results In the non-neurosyphilis group,there were 25 males and 32 females,aged 22 to 76 years;in the asymptomatic neurosyphilis group,there were 10 males and 7 females,aged 26 to 66 years.There were no significant differences in the gender and age distribution between the two groups(both P>0.05).The serum fibronectin levels(486.0[387.5,605.0]mg/L)and serum non-specific antibody titers(base-2 logarithmic transformation[-log2 titer]:5[4,6])in the asymptomatic neurosyphilis group were both significantly higher than those in the non-neurosyphilis group(410.0[347.5,474.5]mg/L,3[1,4],Z=2.36,4.43,respectively,both P<0.05).The areas under the ROC curves of serum fibronectin alone,non-treponemal antibody titers alone,and the two indicators in combination for the diagnosis of asymptomatic neurosyphilis were 0.689(95%CI:0.540-0.838),0.850(95%CI:0.757-0.942),and 0.878(95%CI:0.787-0.970)respectively.Binary logistic regression analysis showed that serum fibronectin levels and non-treponemal antibody titers were associated with the occurrence of asymptomatic neurosyphilis in serofast syphilis patients(both P<0.05).Based on the binary logistic regression analysis,a model equation was obtained as follows:Logit(P)=0.008×serum fibronectin levels+0.090×reciprocal titers of serum non-treponemal antibodies-6.483,when the Logit(P)≥-0.703,it suggested a high probability of asymptomatic neurosyphilis.The cut-off value with 100%sensitivity and the highest specificity was selected,and the probability of patients having asymptomatic neurosyphilis was 0 when the Logit(P)≤-2.863.According to the above new prediction model,asymptomatic neurosyphilis could be excluded in 19(25.68%)patients with serofast syphilis.Conclusion The combination of serum fibronectin with non-treponemal antibody titers showed certain diagnostic value among patients with serofast syphilis,which could help predict and exclude some patients with serofast asymptomatic neurosyphilis.