Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis
Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis
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DOI：
10.1038/s41598-020-60450-3
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发表时间：
2020-02-25
影响因子：
4.6
通讯作者：
Naka, Tetsuji
中科院分区：
文献类型：
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作者：
Fujimoto, Minoru;Matsumoto, Tomoshige;Naka, Tetsuji
由结核分枝杆菌（Mtb）引起的结核病是一个全球性的健康问题。目前，可以通过基于血液的干扰素- γ释放试验（IGRA）来确定先前接触结核杆菌，但活动性结核并不总是通过诸如CRP和ESR之类的血液检测来检测。本研究旨在探讨富亮氨酸α -2糖蛋白（LRG）这一新的炎症生物标志物是否可用于评估结核病活动性疾病。用卡介苗（Bacille Calmette-Guerin， BCG）和未接种卡介苗（Bacille Calmette-Guerin， BCG）的食蟹猴接种Mtb诱导活动性结核。随着时间的推移，从这些动物身上收集血液，量化LRG、CRP和ESR的水平。在未接种卡介苗的猕猴中，Mtb接种引起广泛的结核病，并显著增加血浆CRP和LRG水平，但不增加ESR。在接种卡介苗的猕猴中，尽管结核分枝杆菌引起肺结核，但只有LRG水平显著升高。肺组织免疫组化分析显示，LRG在肉芽组织上皮样细胞和巨细胞中可见。在人类中，结核病患者的血清LRG水平显著高于健康对照者，并在抗结核治疗一个月后下降。这些发现表明，在IGRA之后进行LRG检测活动性结核病是一种很有前景的生物标志物。
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB.