Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America.
PLoS Negl Trop Dis. 2011 Sep;5(9):e1303. doi: 10.1371/journal.pntd.0001303. Epub 2011 Sep 6.
Leprosy is a disease of the skin and peripheral nervous system caused by the obligate intracellular bacterium Mycobacterium leprae. The clinical presentations of leprosy are spectral, with the severity of disease determined by the balance between the cellular and humoral immune response of the host. The exact mechanisms that facilitate disease susceptibility, onset and progression to certain clinical phenotypes are presently unclear. Various studies have examined lipid metabolism in leprosy, but there has been limited work using whole metabolite profiles to distinguish the clinical forms of leprosy.
In this study we adopted a metabolomics approach using high mass accuracy ultrahigh pressure liquid chromatography mass spectrometry (UPLC-MS) to investigate the circulatory biomarkers in newly diagnosed untreated leprosy patients. Sera from patients having bacterial indices (BI) below 1 or above 4 were selected, subjected to UPLC-MS, and then analyzed for biomarkers which distinguish the polar presentations of leprosy. We found significant increases in the abundance of certain polyunsaturated fatty acids (PUFAs) and phospholipids in the high-BI patients, when contrasted with the levels in the low-BI patients. In particular, the median values of arachidonic acid (2-fold increase), eicosapentaenoic acid (2.6-fold increase) and docosahexaenoic acid (1.6-fold increase) were found to be greater in the high-BI patients.
Eicosapentaenoic acid and docosahexaenoic acid are known to exert anti-inflammatory properties, while arachidonic acid has been reported to have both pro- and anti-inflammatory activities. The observed increase in the levels of several lipids in high-BI patients may provide novel clues regarding the biological pathways involved in the immunomodulation of leprosy. Furthermore, these results may lead to the discovery of biomarkers that can be used to investigate susceptibility to infection, facilitate early diagnosis and monitor the progression of disease.
麻风病是一种由麻风分枝杆菌引起的皮肤和周围神经系统疾病。麻风病的临床表现呈光谱性，疾病的严重程度取决于宿主的细胞和体液免疫反应的平衡。目前尚不清楚哪些确切的机制促进了疾病的易感性、发病和向特定临床表型的进展。各种研究已经检查了麻风病中的脂质代谢，但使用全代谢物谱来区分麻风病的临床形式的工作有限。
在这项研究中，我们采用代谢组学方法，使用高质量精度的超高压液相色谱质谱（UPLC-MS）来研究新诊断的未经治疗的麻风病患者的循环生物标志物。选择 BI 低于 1 或高于 4 的患者的血清，进行 UPLC-MS 处理，然后分析可区分麻风病极性表现的生物标志物。我们发现，与低 BI 患者相比，高 BI 患者中某些多不饱和脂肪酸（PUFA）和磷脂的丰度显著增加。特别是，在高 BI 患者中，花生四烯酸（增加 2 倍）、二十碳五烯酸（增加 2.6 倍）和二十二碳六烯酸（增加 1.6 倍）的中位数值较高。
二十碳五烯酸和二十二碳六烯酸具有抗炎特性，而花生四烯酸已被报道具有促炎和抗炎活性。在高 BI 患者中几种脂质水平的观察增加可能为涉及麻风病免疫调节的生物学途径提供新的线索。此外，这些结果可能导致发现可用于研究感染易感性、促进早期诊断和监测疾病进展的生物标志物。
