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γ-干扰素释放试验结果的评价与定量界值的探索
Evaluation for Results of Interferon-gamma Release Assay and the Exploration of Cut-off Value
【作者】 陈诚;
【导师】 张秀伟;
【作者基本信息】 南京医科大学 , 内科学(呼吸系病)(专业学位), 2018, 硕士
【摘要】 结核病是由结核分枝杆菌感染人体后引起的慢性传染病,目前可分为结核潜伏感染、活动性结核、非活动性结核。当机体免疫降低,引起临床发病,及活动性结核,其中肺结核最为常见,肺结核在病原学上可分为菌阳肺结核、分子生物学阳性肺结核、菌阴肺结核。其中菌阴肺结核因病原学难以找到阳性结果,故诊断较为复杂,需结合症状、体征、影像学、外周血指标辅助诊断,必要时试验性抗炎及抗结核治疗。目前临床上可用于结核辅助诊断的指标为结核菌素皮肤试验、结核抗体及新近出现的 Y-干扰素释放试验(interferon-gamma release assay,IGRA)。γ-干扰素释放试验是利用人体感染结核后产生效应T细胞,当其再次接触相关特异性抗原时,可产生大量Y-干扰素,间接反映是否感染结核。目的通过对IGRA检测结果的评价从而评估其在结核病诊断中的应用价值,分析导致IGRA检测结果的假阳性的危险因素,并探索鉴别诊断活动性肺结核与其它呼吸系统疾病更保守的定量界值(cut-off值)。方法选取2016年09月至2017年09月我院呼吸内科及结核门诊所有进行IGRA检测的患者,并记录病例基本情况(年龄、性别)、诊断信息、IGRA定量值及结果判定。计算IGRA诊断的敏感度、特异度、阳性预测值、阴性预测值,并分析假阳性的可能原因。此外,选取IGRA检测阳性结果,探索预测一个鉴别活动性肺结核与假阳性结果的定量界值(cut-off值)。结果基于我院呼吸科及结核门诊2016年至2017年度符合纳排标准1234例IGRA检测样本得出IGRA检测的敏感度和特异度分别为:84.7%和78.6%,阳性预测值为28.1%,阴性预测值为98.1%。陈旧性肺结核是导致IGRA检测结果假阳性的重要危险因素。基于IGRA阳性样本定量检测结果计算的cut-off值为 80.2。结论IGRA对于诊断活动性肺结核有较高的敏感度与特异度,具有较高的诊断价值,但其阳性预测值较低,即存在较高的假阳性率。对于IGRA检测阳性样本,但其它辅助检查手段不提示结核的患者可结合IGRA定量结果进行辅助判断,并以80.2作为cut-off值提供鉴别诊断参考依据。
【Abstract】 Tuberculosis is a chronic infectious disease caused by the infection of mycobacterium tuberculosis.At present,it can be divided into latent tuberculosis infection,active tuberculosis and inactive tuberculosis.It can cause clinical active tuberculosis when organism immunity decreased.Pulmonary tuberculosis is commonest.Pulmonary tuberculosis can be divided into culture positive pulmonary tuberculosis,molecular biology positive pulmonary tuberculosis,culture negative pulmonary tuberculosis.The diagnosis of active pulmonary tuberculosis is complicated,because it is difficult to find etiological positive results.It needs to be assisted in diagnosis by combining symptoms,physical signs,imaging and peripheral blood test,and experimental anti-inflammatory and anti-tuberculosis treatment when necessary.At present,tests that can be used for the auxiliary diagnosis of tuberculosis on the market are tuberculin skin test,tuberculous antibody and interferon-gamma release assay.After being infected with mycobacterium tuberculosis,human body can produce effector T cells.When contacting with the relevant specific antigens again,the effector T cells can produce a lot of interferon-gamma,indirectly reflecting whether infected with mycobacterium tuberculosis.Objective To evaluate the application value of interferon-gamma release assay(IGRA)in tuberculosis diagnosis,and to explore the related cut-off value of the diagnosis of active tuberculosis.Methods Selecting patients who have taken IGRA test from department of respiratory medicine and tuberculosis clinic from September 2016 to September 2017。Basic information such as age,sex,clinical diagnosis,quantitative and qualitative result of IGRA be collected for analysis.Calculating IGRA diagnostic sensitivity,specificity,positive predictive value,negative predictive value,and analyzes the possible reason for false positive.In addition,the positive results of IGRA will be selected to explore a quantitative boundary value(cut-off value)for the identification of active tuberculosis and false positive results.Results Based on 1234IGRA test samples of respiratory department and tuberculosis outpatient department of our hospital that met the admission standard,the sensitivity and specificity of IGRA detection in IGRA were obtained from the IGRA test samples of department of respiratory medicine and TB clinic in 2017 are 84.7%and 78.6%,respectively from 2016 to 2017.The positive predictive value was 28.1%,and the negative predictive value was 98.1%.Old tuberculosis is an important risk factor that results in false positive results of IGRA.The diagnostic boundary value(cut-off value)of the quantitative test results based on IGRA positive sample was 80.2.Conclusion IGRA has high sensitivity and specificity for the diagnosis of active pulmonary tuberculosis,and it has higher diagnostic value,but its positive predictive value is lower,which means higher false positive rate.For IGRA test positive samples,the patients who did not indicate TB can be assisted by the IGRA quantitative results,and 80.2 as the cut-off value to provide the reference basis of differential diagnosis.