Bacterial Diseases Programme, Medical Research Council (United Kingdom) Laboratories, Fajara, The Gambia.
PLoS One. 2010 Sep 1;5(9):e12502. doi: 10.1371/journal.pone.0012502.
Qualitative and quantitative changes in IGRA response offer promise as biomarkers to monitor Tuberculosis (TB) drug therapy, and for the comparison of new interventions. We studied the decay kinetics of TB-specific antigen T-cell responses measured with an in-house ELISPOT assay during the course of therapy.
Newly diagnosed sputum smear positive TB cases with typical TB chest radiographs were recruited. All patients were given standard anti-TB treatment. Each subject was followed up for 6 months and treatment outcomes were documented. Blood samples were obtained for the ESAT-6 and CFP-10 (EC) ELISPOT at diagnosis, 1-, 2-, 4- and 6-months. Qualitative and quantitative reversion of the ELISPOT results were assessed with McNemar test, conditional logistic regression and mixed-effects hierarchical Poisson models.
A total of 116 cases were recruited and EC ELISPOT was positive for 87% (95 of 109) at recruitment. There was a significant decrease in the proportion of EC ELISPOT positive cases over the treatment period (p<0.001). Most of the reversion occurred between the start and first month of treatment and at completion at 6 months. ESAT-6 had higher median counts compared to CFP-10 at all time points. Counts for each antigen declined significantly with therapy (p<0.001). Reverters had lower median SFUs at the start of treatment compared to non-Reverters for both antigens. Apart from the higher median counts for non-Reverters, no other risk factors for non-reversion were found.
TB treatment induces qualitative and quantitative reversion of a positive in-house IGRA in newly diagnosed cases of active TB disease. As this does not occur reliably in the majority of cured individuals, qualitative and quantitative reversion of an IGRA ELISPOT has limited clinical utility as a surrogate marker of treatment efficacy.
IGRA 反应的定性和定量变化有望成为监测结核病（TB）药物治疗的生物标志物，并可用于比较新的干预措施。我们研究了在治疗过程中使用内部 ELISPOT 测定法测量的 TB 特异性抗原 T 细胞反应的衰减动力学。
招募了新诊断的痰涂片阳性、具有典型 TB 胸片的肺结核病例。所有患者均给予标准抗 TB 治疗。对每位患者进行 6 个月的随访，并记录治疗结果。在诊断时、1 个月、2 个月、4 个月和 6 个月时采集 ESAT-6 和 CFP-10（EC）ELISPOT 的血液样本。采用 McNemar 检验、条件逻辑回归和混合效应分层泊松模型评估 ELISPOT 结果的定性和定量逆转。
共招募了 116 例患者，在招募时，EC ELISPOT 阳性率为 87%（109 例中的 95 例）。在治疗期间，EC ELISPOT 阳性病例的比例显著下降（p<0.001）。大多数逆转发生在治疗开始和第一个月之间，在 6 个月时完成。在所有时间点，ESAT-6 的中位数计数均高于 CFP-10。随着治疗的进行，两种抗原的计数均显著下降（p<0.001）。与非逆转者相比，逆转者在开始治疗时的中位数 SFU 较低。除了非逆转者的中位数计数较高外，未发现其他非逆转的危险因素。
TB 治疗可诱导新诊断的活动性 TB 疾病患者中阳性内部 IGRA 的定性和定量逆转。由于在大多数治愈的个体中这不能可靠地发生，因此，IGRA ELISPOT 的定性和定量逆转作为治疗效果的替代标志物具有有限的临床实用性。
