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Abstract：
BACKGROUND: Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobacterial survival. The plasma Kyn-to-Trp (K/T) ratio is a potential TB diagnostic and/or predictive biomarker in PWH on long-term antiretroviral therapy (ART).
METHODS: We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry.
RESULTS: The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069-0.123) compared to controls (0.055; IQR 0.045-0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB (p = 0.005), but there was no correlation in controls.
CONCLUSIONS: The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts.
BACKGROUND: ClinicalTrials.gov Identifier: NCT00411983.
METHODS: We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry.
RESULTS: The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069-0.123) compared to controls (0.055; IQR 0.045-0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB (p = 0.005), but there was no correlation in controls.
CONCLUSIONS: The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts.
BACKGROUND: ClinicalTrials.gov Identifier: NCT00411983.
摘要：
背景：需要非基于痰的测试来预测或诊断HIV感染者（PWH）的结核病（TB）疾病。吲哚胺2，3-双加氧酶-1（IDO1）在结核性肉芽肿中表达，并将色氨酸（Trp）分解代谢为犬尿氨酸（Kyn）。IDO1活性损害先天和适应性免疫反应，促进分枝杆菌生存。血浆Kyn与Trp（K/T）比率是长期抗逆转录病毒疗法（ART）的PWH中潜在的TB诊断和/或预测性生物标志物。
方法：我们比较了PWH样品中的血浆K/T比率，他们接受了前瞻性随访，并在ART开始后发展为结核病。对照的年龄和ART持续时间相匹配。在3个时间点测量Kyn和Trp；在结核病诊断时，结核病诊断前6个月和结核病诊断后6个月，采用超高效液相色谱与质谱联用。
结果：结核病患者在诊断时的K/T比值较高（中位数，0.086;IQR,0.069-0.123）与对照组（0.055；IQR0.045-0.064；p=0.006）相比，但不是在结核病诊断之前或之后。结核病治疗成功后K/T比值显著下降，但在治疗失败时增加。K/T比值与结核病参与者的CD4细胞计数呈抛物线相关性（p=0.005），但对照组没有相关性。
结论：血浆K/T比值有助于识别TB疾病，并可作为监测PWH中TB治疗的辅助生物标志物。应在精心设计的前瞻性队列中进行验证研究，以确定这些发现并评估PWH中结核病诊断的最佳截止值。
背景：ClinicalTrials.gov标识符：NCT00411983。
方法：我们比较了PWH样品中的血浆K/T比率，他们接受了前瞻性随访，并在ART开始后发展为结核病。对照的年龄和ART持续时间相匹配。在3个时间点测量Kyn和Trp；在结核病诊断时，结核病诊断前6个月和结核病诊断后6个月，采用超高效液相色谱与质谱联用。
结果：结核病患者在诊断时的K/T比值较高（中位数，0.086;IQR,0.069-0.123）与对照组（0.055；IQR0.045-0.064；p=0.006）相比，但不是在结核病诊断之前或之后。结核病治疗成功后K/T比值显著下降，但在治疗失败时增加。K/T比值与结核病参与者的CD4细胞计数呈抛物线相关性（p=0.005），但对照组没有相关性。
结论：血浆K/T比值有助于识别TB疾病，并可作为监测PWH中TB治疗的辅助生物标志物。应在精心设计的前瞻性队列中进行验证研究，以确定这些发现并评估PWH中结核病诊断的最佳截止值。
背景：ClinicalTrials.gov标识符：NCT00411983。
