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中华肺部疾病杂志(电子版) ›› 2020, Vol. 13 ›› Issue (03) : 334 -339. doi: 10.3877/cma.j.issn.1674-6902.2020.03.009

论著

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
宋韬1, 付洪义2, 李莉娟3,(), 耿书军1, 侯莉莉1, 康冠楠1   
  1. 1. 050041 石家庄,河北省胸科医院结核内科
    2. 050041 石家庄,河北省胸科医院医务处
    3. 050004 石家庄,白求恩国际和平医院干部一科
  • 收稿日期:2020-02-15 出版日期:2020-06-25
  • 通信作者: 李莉娟
  • 基金资助:
    河北省青年科技课题(1020140373)

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

Tao Song1, Hongyi Fu2, Lijuan Li3,(), Shujun Geng1, Lili Hou1, Guannan Kang1   

  1. 1. Department of TB Medicine, Hebei Chest Hospital, Shijiazhuang 050041, China
    2. Medical Office, Hebei Chest Hospital, Shijiazhuang 050041, China
    3. First Department of Cadre′s Ward, Bethune International Peace Hospital of Chinese PLA, Shijiazhuang 050004, China
  • Received:2020-02-15 Published:2020-06-25
  • Corresponding author: Lijuan Li
引用本文:

宋韬, 付洪义, 李莉娟, 耿书军, 侯莉莉, 康冠楠. 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[J/OL]. 中华肺部疾病杂志(电子版), 2020, 13(03): 334-339.

Tao Song, Hongyi Fu, Lijuan Li, Shujun Geng, Lili Hou, Guannan Kang. 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[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(03): 334-339.

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).

Results

①The 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.

表1 T-SPOT.TB检测对PTB的诊断价值分析
图1 抗原CFP10、抗原ESAT-6诊断PTB合并DM的ROC曲线分析
表2 各组抗原CFP10、抗原ESAT-6原值比较(±s,SFCs/2.5×105PBMC)
表3 各组血清25-(OH)D3及LL-37水平比较(±s,ng/ml)
图2 25-(OH)D3 ROC曲线分析
图3 LL-37 ROC曲线分析
表4 T-SPOT.TB联合血清25-(OH)D3、LL-37诊断PTB合并DM的价值
1
方源扬,刘国强,黄显聪,等. 景东县2004-2013年肺结核防治的卫生经济学分析[J/CD]. 中华肺部疾病杂志(电子版), 2016, 9(1): 36-40.
2
任成山,林 辉,杨仕明. 结核病的流行特征与耐多药的窘迫及其策略[J/CD]. 中华肺部疾病杂志(电子版), 2019, 12(3): 269-274.
3
Magee MJ, Foote M, Maggio DM, et al. Diabetes mellitus and risk of all-cause mortality among patients with tuberculosis in the state of Georgia, 2009-2012[J]. Ann Epidemiol, 2014, 24(5): 369-375.
4
Shen TC, Lin CL, Wei CC, et al. Increased risk of tuberculosis in patients with type 1 diabetes mellitus[J]. Medicine, 2014, 93(16): 96-101.
5
Mi F, Jiang G, Du J, et al. Is resistance to anti-tuberculosis drugs associated with type 2 diabetes mellitus? A register review in Beijing, China[J]. Global Health Action, 2014, 7(1): 24022-24029.
6
Kumar AK, Chandrasekaran V, Kannan T, et al. Anti-tuberculosis drug concentrations in tuberculosis patients with and without diabetes mellitus.[J]. Eur J Clin Pharmacol, 2016, 73(1): 1-6.
7
孔忠顺,黄麦玲,刘荣梅,等. 糖尿病合并初治肺结核患者临床特点[J]. 中国糖尿病杂志,2014, 6(5): 329-331.
8
米佳丽,尹怀文,张 兴. 2型糖尿病患者肺结核的临床特点分析[J]. 中华医院感染学杂志,2014, 24(8): 1940-1942.
9
Lacourse SM, Chester FM, Preidis G, et al. Use of Xpert for The diagnosis of pulmonary tuberculosis in severely malnourished hospitalized malawian children[J]. Pediatr Infect Dis J, 2014, 33(11): 1200-1202.
10
Di L, Li Y. The risk factor of false-negative and false-positive for T-SPOT.TB in active tuberculosis[J]. J Clin Lab Anal, 2017, 31(2): e22273-e22273.
11
Seo KW, Ahn JJ, Ra SW, et al. Persistently Retained Interferon-Gamma Responsiveness in Individuals with a History of Pulmonary Tuberculosis[J]. Tohoku J Exp Med, 2014, 233(2): 123-128.
12
中华医学会结核病学分会. 肺结核诊断和治疗指南[J]. 中华结核和呼吸杂志,2001, 20(2): 70-74.
13
美国糖尿病协会. 美国糖尿病协会糖尿病完全指南[M]. 北京:北京科学技术出版社,2014: 29-33.
14
Kumar NP, Babu S. Influence of diabetes mellitus on the immunity to human tuberculosis[J]. Immunology, 2017, 152(1): 13-24.
15
Da Costa JC, Oliveira O, Baa L, et al. Prevalence and factors associated with diabetes mellitus among tuberculosis patients: A nationwide cohort[J]. Eur Respir J, 2016, 48(1): ERJ-00254-2016.
16
Denkinger CM, Schumacher SG, Boehme CC, et al. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis[J]. Eur Respir J, 2014, 44(2): 435-446.
17
Bojang AL, Mendy FS, Tientcheu LD, et al. Comparison of TB-LAMP, GeneXpert MTB/RIF and culture for diagnosis of pulmonary tuberculosis in The Gambia[J]. J Infect Chemother, 2015, 72(3): 332-337.
18
Cai R, Chen J, Guan L, et al. Relationship between T-SPOT.TB responses and numbers of circulating CD4+ T-cells in HIV infected patients with active tuberculosis[J]. Biosci Trends, 2014, 8(3): 163-168.
19
Arenas M, Hidalgo-Tenorio C, Jimenez-Gamiz P, et al. Diagnosis of Latent Tuberculosis in Patients with Systemic Lupus Erythematosus: T.SPOT.TB versus Tuberculin Skin Test[J]. Biomed Res Int, 2014, 2: 1-8.
20
管立学,朱 芸,盖林林,等. 免疫性疾病患者T-SPOT.TB筛查结果及影响因素[J]. 山东大学学报(医学版), 2016, 54(6): 82-86.
21
刘佳庆,张丽霞,秦中华,等. Xpert MTB/RIF和T-SPOT.TB对涂阴肺结核诊断价值的评估[J]. 临床检验杂志,2016, 34(10): 755-757.
22
石学萍,王 晶,王 鑫,等. 结核分枝杆菌感染T细胞斑点试验在疑诊肺结核患者中的临床应用[J]. 解放军医学杂志,2017, 42(11): 70-74.
23
蔺景双,蔺 晨,郝兴亮,等. 结核感染T细胞斑点试验诊断肺结核的临床应用[J]. 山东医药,2016, 56(48): 99-101.
24
Akhirunnesa M, Sultana RR, Mostafa KSM, et al. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial[J]. PLOS One, 2015, 10(9): 1-25.
25
范乐平,郭慕新,张 玥,等. 血清25羟维生素D3与糖尿病视网膜病变的相关性研究[J]. 营养学报,2017, 39(2): 139-143.
26
李文和,张丽娟,胡译方,等. 2型糖尿病患者血清25羟基维生素D与糖尿病肾脏疾病的相关性研究[J]. 中国糖尿病杂志,2018, 26(5): 402-406.
27
石 洁,朱岩昆,郑丹薇,等. 维生素D受体基因多态性与环境因素交互作用对河南省结核病发病影响[J]. 现代预防医学,2017, 17(11): 174-178.
28
Sinha S, Gupta K, Mandal D, et al. Serum and Bronchoalveolar Lavage Fluid 25(OH)Vitamin D3 Levels in HIV-1 and Tuberculosis: A Cross-Sectional Study from a Tertiary Care Center in North India.[J]. Curr Hiv Res, 2018, 16(2): 167-173.
29
罗光燕,杨小琼,张 芸,等. 25羟维生素D3与抗菌肽在反复上呼吸道感染中的作用研究及相关性分析[J]. 重庆医学,2016, 45(29): 4053-4055.
30
喻 文,罗红敏. 维生素D3对脓毒症患者维生素D和抗菌肽水平的影响:一项随机安慰剂对照试验[J]. 中华危重病急救医学,2016, 28(2): 98-98.
31
Afsal K, Harishankar M, Banurekha VV, et al. Effect of 1,25-dihydroxy vitamin D3 on cathelicidin expression in patients with and without cavitary tuberculosis[J]. Tuberculosis, 2014, 94(6): 599-605.
32
战云飞. 维生素D、LL-37和细胞因子在糖尿病合并肺结核患者的水平研究[D]. 山东大学,2014: 12-23.
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