T-SPOT.TB联合血清25-(OH)D3、LL-37诊断肺结核合并糖尿病的价值分析

Value of T-cell spot of tuberculosis combined with serum 25-dihydroxycholecalciferol D3 and antimicrobial peptide LL-37 in diagnosis of pulmonary tuberculosis with diabetes mellitus

目的分析结核杆菌T细胞斑点实验(T-SPOT.TB)联合血清25-羟基维生素D3[25-(OH)D3]、抗菌肽LL-37诊断肺结核(PTB)合并糖尿病(DM)的价值。方法回顾性分析2015年1月至2018年12月在本院行T-SPOT.TB实验及血清25-(OH)D3、LL-37检测的340例疑似PTB患者的临床资料,其中121例确诊PTB患者纳入PTB组,97例确诊PTB合并DM患者纳入PTB-DM组,另122例排除MTB感染及DM患者纳入对照组;比较各组特异性抗原培养滤液蛋白10(CFP10)、6000早期分泌性抗原靶(ESAT-6)孔内斑点形成细胞(SFCs)数量及血清25-(OH)D3、LL-37水平;绘制受试者操作特征曲线(ROC曲线)分析T-SPOT.TB联合血清25-(OH)D3、LL-37诊断PTB合并DM的价值。结果①T-SPOT.TB诊断PTB的总敏感度为76.6%、特异度为77.0%、准确率76.8%、阳性预测值85.6%、阴性预测值64.8%、kappa 0.515,一致性一般;②PTB-DM组抗原CFP10、抗原ESAT-6孔内SFCs>PTB组>对照组(P<0.05),抗原CFP10及抗原ESAT-6孔SFCs曲线下面积(AUC)分别为0.871、0.872;cut-off分别为16.13 SFCs/2.5×105 PBMC、14.80 SFCs/2.5×105 PBMC,联合诊断时AUC为0.931,敏感度83.5%,特异度87.2%;③PTB-DM组血清25-(OH)D3<PTB组<对照组,LL-37>PTB组>对照组(均P<0.05),AUC分别为0.630、0.653,cut-off为18.06 ng/ml、59.71 ng/ml,诊断PTB合并DM的敏感度为90.7%、45.4%,特异度为33.3%、91.4%;④T-SPOT.TB联合25-(OH)D3、LL37诊断时AUC值最大,为0.933,敏感度为79.4%、特异度92.2%。结论单一T-SPOT.TB诊断对PTB合并DM效能不佳,若联合血清25-(OH)D3、LL-37诊断或可提升诊断效能,为PTB合并DM患者的临床治疗提供更高价值的参考意见,值得临床重视。

Objective To analyze the value of T-cell spot of tuberculosis(T-SPOT.TB)combined with serum 25-dihydroxycholecalciferol D3[25-(OH)D3]and antimicrobial peptide LL-37 in the diagnosis of pulmonary tuberculosis(PTB)with diabetes mellitus(DM).Methods The clinical data of 340 patients with suspected PTB who underwent T-SPOT.TB and detection of serum 25-(OH)D3 and LL-37 in our hospital from January 2015 to December 2018 were retrospectively analyzed.A total of 121 patients with only PTB were enrolled in the PTB group,while 97 patients with PTB and DM were enrolled in the PTB-DM group.And the 122 patients without PTB infection or DM were included in the control group.The levels of specific antigen culture filtrate protein 10(CFP10),the number of spot forming cells(SFCs)in the 6000 early secretion antigen target(ESAT-6),and the levels of serum 25-(OH)D3 and LL-37 were compared among the three groups.The values of T-SPOT.TB combined with serum 25-(OH)D3 and LL-37 in the diagnosis of PTB with DM were analyzed through drawing the receiver operating characteristic curve(ROC curve).Results①The total sensitivity,specificity,accuracy,positive predictive value,negative predictive value and kappa value of T-SPOT.TB for the diagnosis of PTB were 76.6%,77.0%,76.8%,85.6%,64.8%and 0.515,respectively,indicating general consistency.②Antigen CFP10 and SFCs in the antigen ESAT-6 were the highest in the PTB-DM group,followed by the PTB group and the control group(P<0.05).The areas under the curves(AUCs)of antigen CFP10 and SFCs in the antigen ESAT-6 were 0.871 and 0.872,respectively.The cut-off values were 16.13 SFCs/2.5×105 PBMC and 14.80 SFCs/2.5×105 PBMC,respectively.The AUC,sensitivity and specificity of the combined diagnosis were 0.931,83.5%and 87.2%,respectively.③The level of serum 25-(OH)D3 was the lowest in the PTB-DM group,followed by the PTB group and the control group,while the level of LL-37 was the highest in the PTB-DM group,followed by the PTB group and the control group(all P<0.05).The AUCs were 0.630 and 0.653,respectively.The cut-off values were 18.06 ng/ml and 59.71 ng/ml,respectively.The sensitivity and specificity for the diagnosis of PTB with DM were(90.7%,45.4%)and(33.3%,91.4%),respectively.④The AUC of T-SPOT.TB combined with 25-(OH)D3 and LL37 was the largest(0.933),with the sensitivity and specificity of 79.4%and 92.2%,respectively.Conclusion Single T-SPOT.TB diagnosis is not effective for PTB with DM.T-SPOT.TB combining with serum 25-(OH)D3 and LL-37 can improve the diagnostic efficiency,which provides references for the clinical treatment of the patients with PTB and DM.