细胞毒T淋巴细胞相关抗原-4对活动与潜伏结核感染的鉴别诊断价值评估

摘要

目的 分析细胞毒T淋巴细胞相关抗原-4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)在活动性结核(active tuberculosis,ATB)与潜伏性结核感染(latent tuberculosis infection,LTBI)患者外周血中的表达情况,评价其在ATB与LTBI中的鉴别诊断价值.方法 收集2011年1月至2013年3月无锡市第五人民医院和复旦大学附属华山医院连续入选的48例患者,其中LTBI患者18例和ATB患者30例.应用流式细胞术对48例患者CD4+CD25+FoxP3+T淋巴细胞CTLA-4的表达情况进性检测,采用非参数Mann-Whitney U检验对CTLA-4表达水平进行比较.结果 ATB患者表达CTLA-4的CD4+CD25+FoxP3+Treg占CD4+CD25+FoxP3+Treg的百分比中位数为18.95％(13.86％,27.73％);而LTBI患者CTLA-4表达的中位数为6.67％(5.74％,9.59％),两组比较差异有统计学意义(U=18.0,P<0.01).根据CTLA-4表达量进行受试者工作特征曲线分析,其曲线下面积为0.96,最佳阈值为13.25％.诊断活动性结核的敏感度为86.7％,特异度为94.4％.结论 CTLA-4用于鉴别诊断γ干扰素释放试验阳性患者ATB与LTBI具有较高的敏感度和特异度,为进一步研究ATB的发病机制提供有意义的线索.%Objective To analyze the expressions of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the peripheral blood of patients with active tuberculosis (ATB ) or latent tuberculosis infection (LTBI) ,and to evaluate its diagnostic value in differentiation of ATB and LTBI .Methods Forty-eight patients including 18 ATB cases and 30 LTBI cases were continuously enrolled from Wuxi No . 5 People′s Hospital and Huashan Hospital affiliated to Fudan University from January 2011 to March 2013 .Flow cytometry was applied to detect the CTLA-4 expression in CD4+CD25+ FoxP3+ T cells in the peripheral blood of the 48 subjects .CTLA-4 levels were compared using non-parametric Mann-Whitney U test .Results The median percentage of CTLA-4+ Treg in CD4+ CD25+ Foxp3+ Treg cells of ATB patients was 18 .95％ (quantile range :13 .86％ ,27 .73％ ) ,and that in LTBI patients was 6 .67％(quantile range :5 .74％ ,9 .59％ ) ,which was statistically significant (U=18 .0 , P< 0 .01) .Receiver operating curve (ROC) based on the CTLA-4 expression indicated that the area under the curve was 0 .96 , with the optimum cut-off value of 13 .25％ .Thus ,the sensitivity and specificity for the diagnosis of ATB were 86 .7％ and 94 .4％ ,respectively .Conclusion CTLA-4 has highly sensitivity and specificity for the differential diagnosis of ATB and LTBI whose interferon-gamma releasing assays are all positive ,which may also provide meaningful clue for the study of pathogenesis of ATB .