Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.
Meditation, AIDS, Health, Addiction & Nutrition (MAHAN) Trust, C/O Mahatma Gandhi Tribal Hospital, Karmagram, Utavali, Tahsil Dharni, Amravati, Maharashtra, India.
J Infect Public Health. 2015 Jul-Aug;8(4):329-40. doi: 10.1016/j.jiph.2015.02.003. Epub 2015 Mar 29.
The tuberculin skin test (TST) and interferon-gamma release assays (IGRA), namely, the QuantiFERON-TB Gold test (QFT), remain the standard immunological diagnostic tools for latent tuberculosis (TB) infection (LTBI). However, the sub-optimal detection rates of both of these tests are major impediments in recognizing the population at risk. This study was aimed at evaluating additional cytokines besides interferon-gamma (IFN-γ) as biomarkers for improving LTBI diagnosis in the tribal population of Melghat, India. Seventy-four close TB contacts were stratified by QFT and TST results into: (i) QFT+/TST+ (n = 26), (ii) QFT+/TST- (n = 12), (iii) QFT-/TST- (n = 35) and (iv) QFT-/TST+ (n = 1) groups. A panel of cytokines (IL-6, IL-10, TNF-α and IL-2R) was then evaluated in antigen-stimulated QFT cell-free culture supernatants using IMMULITE-1000, an automated immunoassay analyzer. Cytokine estimation showed significantly higher levels of IL-6 in the QFT+/TST+ group, while significantly higher levels of IL-10 were found in the QFT-/TST- group. Correlation analysis identified a positive correlation between IL-6 and the QFT response (r = 0.6723, P < 0.0001), while a negative correlation was seen between QFT and IL-10 expression (r = -0.3271, P = 0.0044). Similarly, IL-6 was positively correlated with TST levels (r = 0.6631, P <0 .0001), and conversely, a negative correlation was found between TST and IL-10 expression (r = -0.5698, P < 0.0001). The positive and negative predictive values of IL-6 were found to be 92.59 and 93.33%, respectively, and the positive and negative predictive values of IL-10 were 96.55 and 91.18%, respectively. No significant impact of the demographic characteristics on cytokine positivity was observed. Our preliminary results suggest that the evaluation of additional cytokines in QFT cell-free culture supernatants may be valuable for the identification of LTBI. Combining IL-6 and IL-10 with QFT and/or TST could markedly improve the detection accuracy of LTBI. Our observations require investigation in larger well-characterized cohorts along with follow-up studies to further confirm the study outcome.
结核菌素皮肤试验（TST）和干扰素-γ释放测定（IGRA），即 QuantiFERON-TB Gold 试验（QFT），仍然是潜伏性结核感染（LTBI）的标准免疫学诊断工具。然而，这两种检测方法的检测率都不理想，这是识别高危人群的主要障碍。本研究旨在评估干扰素-γ（IFN-γ）以外的其他细胞因子作为生物标志物，以提高印度 Melghat 部落人群 LTBI 的诊断率。74 名密切接触结核病的患者按 QFT 和 TST 结果分为：（i）QFT+/TST+（n=26）、（ii）QFT+/TST-（n=12）、（iii）QFT-/TST-（n=35）和（iv）QFT-/TST+（n=1）组。然后，使用 IMMULITE-1000 自动免疫分析仪评估抗原刺激 QFT 无细胞培养上清液中的细胞因子（IL-6、IL-10、TNF-α和 IL-2R）。细胞因子测定显示，QFT+/TST+组的 IL-6 水平显著升高，而 QFT-/TST-组的 IL-10 水平显著升高。相关性分析发现 IL-6 与 QFT 反应呈正相关（r=0.6723，P<0.0001），而 QFT 与 IL-10 表达呈负相关（r=-0.3271，P=0.0044）。同样，IL-6 与 TST 水平呈正相关（r=0.6631，P<0.0001），而 TST 与 IL-10 表达呈负相关（r=-0.5698，P<0.0001）。IL-6 的阳性和阴性预测值分别为 92.59%和 93.33%，IL-10 的阳性和阴性预测值分别为 96.55%和 91.18%。细胞因子阳性与人口统计学特征无显著相关性。我们的初步结果表明，在 QFT 无细胞培养上清液中评估其他细胞因子可能有助于 LTBI 的鉴定。将 IL-6 和 IL-10 与 QFT 和/或 TST 相结合，可以显著提高 LTBI 的检测准确性。我们的观察结果需要在更大的、特征明确的队列中进行研究，并进行随访研究以进一步证实研究结果。
