■目前的免疫学方法无法区分结核分枝杆菌(Mtb)感染状态,特别是区分活动性结核病(ATB)和潜伏性结核病感染(LTBI)。这项研究探索了潜伏期相关抗原(Rv1733cSLP和Rv2028c)和多因素细胞因子检测以区分结核感染状态的潜力。
■ATB患者(20),LTBI医护人员(25),发烧患者(11),纳入健康对照(10)。细胞因子水平(IFN-γ,TNF-α,IL-2,IL-6,IP-10,IL-1Ra,CXCL-1和MCP-1)使用Luminex在有/没有MTB特异性毒力因子和潜伏期相关抗原刺激的情况下进行测量。
■没有抗原刺激,IL-6、IP-10、MCP-1和IL-1Ra在ATB组高于LTBI组(p<0.05),但ATB组与发热组之间无显著差异。用四种抗原刺激,分别,细胞因子,包括IP-10Esat-6,IP-10CFP-10,IFN-γRv1733cSLP,IFN-γRv2028c,IL-6Esat-6,IL-6Rv1733cSLP,IL-6Rv2028c,IL-2Rv1733cSLP,IL-2Rv2028c,IL-1RaEsat-6,IL-1RaCFP-10,IL-1RaRv2028c,CXCL-1Esat-6、CXCL-1CFP-10、CXCL-1Rv1733cSLP、CXCL-1Rv2028c,MCP-1Esat-6和MCP-1CFP-10证实了ATB和LTBI之间的准确区分(p<0.05)。添加剂浓度显示IFN-γ的显着分泌差异,IP-10和IL-2,主要通过ATB中的毒力因子和LTBI中的潜伏期相关抗原。潜伏相关抗原与毒力因子协同作用,增强TH1型细胞因子诊断效能,用于区分ATB和LTBI,TNF-α的AUC从0.696增加到0.820(p=0.038),IFN-γ从0.806增加到0.962(p=0.025),IL-2从0.565增加到0.868(p=0.007)。通过前向似然法选择的模型表明联合检测IFN-γCFP-10,IFN-γRv1733cSLP,IP-10Rv1733cSLP,CXCL-1Rv1733cSLP实现了ATB诊断(AUC=0.996)和ATB-LTBI分化(AUC=0.992)。联合检测IFN-γCFP-10和IFN-γRv1733cSLP可实现结核感染诊断(AUC=0.943)。
■潜伏相关抗原增强多种细胞因子的辨别能力,特别是TH1型细胞因子,用于区分Mtb感染状态。
UNASSIGNED: Current immunologic methods cannot distinguish Mycobacterium tuberculosis (Mtb) infection statuses, especially to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). This study explored the potential of latency-associated antigens (Rv1733cSLP and Rv2028c) and multifactorial cytokine detection to distinguish tuberculosis infection states.
UNASSIGNED: ATB patients (20), LTBI healthcare workers (25), fever patients (11), and healthy controls (10) were enrolled. Cytokine levels (IFN-γ, TNF-α, IL-2, IL-6, IP-10, IL-1Ra, CXCL-1, and MCP-1) were measured using Luminex with/without MTB-specific virulence factor and latency-associated antigens stimulation.
UNASSIGNED: Without antigen stimulation, IL-6, IP-10, MCP-1, and IL-1Ra were higher in the ATB group than in the LTBI group (p<0.05), but no significant differences between the ATB group and the fever group. Stimulated with the four antigens, respectively, the cytokines, including IP-10Esat-6, IP-10CFP-10, IFN-γRv1733cSLP, IFN-γRv2028c, IL-6Esat-6, IL-6Rv1733cSLP, IL-6Rv2028c, IL-2Rv1733cSLP, IL-2 Rv2028c, IL-1RaEsat-6, IL-1RaCFP-10, IL-1RaRv2028c, CXCL-1Esat-6, CXCL-1CFP-10, CXCL-1Rv1733cSLP, CXCL-1Rv2028c, MCP-1Esat-6 and MCP-1CFP-10, demonstrated accurate discrimination between ATB and LTBI (p<0.05). Additive concentrations demonstrated significant secretion differences of IFN-γ, IP-10 and IL-2, primarily by virulence factors in ATB and latency-associated antigens in LTBI. Latency-associated antigens synergized with virulence factors, enhancing TH1-type cytokine diagnostic efficacy for discriminating ATB from LTBI, the AUC for TNF-α increased from 0.696 to 0.820 (p=0.038), IFN-γ increased from 0.806 to 0.962 (p=0.025), and IL-2 increased from 0.565 to 0.868 (p=0.007). Model selected by forward likelihood method indicated combined detection of IFN-γCFP-10, IFN-γRv1733cSLP, IP-10Rv1733cSLP, and CXCL-1Rv1733cSLP achieved ATB diagnosis (AUC=0.996) and ATB-LTBI differentiation (AUC=0.992). Combined detection of IFN-γCFP-10 and IFN-γRv1733cSLP achieved tuberculosis infection diagnosis (AUC=0.943).
UNASSIGNED: Latency-associated antigens enhance multiple cytokine discriminatory ability, particularly TH1-type cytokines, for differentiating Mtb infection statuses.