Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523, United States.
Cellular Microbiology Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro 21040-360, Rio de Janeiro, Brazil.
ACS Infect Dis. 2023 Aug 11;9(8):1458-1469. doi: 10.1021/acsinfecdis.2c00585. Epub 2023 Jul 10.
Intra-household contacts (HCs) of leprosy patients are at increased risk of infection by and about ∼5-10% will develop active disease. A prognostic tool to identify HCs with the greatest risk of progressing to active disease would enhance early leprosy diagnosis and optimize prophylactic intervention. Previous metabolomics studies suggest that host lipid mediators derived from ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are potential biomarkers for leprosy. In this study, we investigated retrospective sera of leprosy HCs by liquid chromatography-mass spectrometry and enzyme-linked immunoassay to determine whether circulating levels of ω-3 and ω-6 PUFA metabolites were altered in HCs that developed leprosy (HCDL) in comparison to those that did not (HCNDL). Sera were collected from HCs at the time of index case diagnosis and before clinical signs/symptoms of leprosy. Our findings showed that HCDL sera exhibited a distinct metabolic profile in comparison to HCDNL. Specifically, arachidonic acid, leukotriene B, 11-hydroxyeicosatetraenoic acid, prostaglandin D, and lipoxin A were elevated in HCDL. In contrast, prostaglandin E levels were reduced in HCDL. The ω-3 PUFAs, docosahexaenoic acid, eicosapentaenoic acid, and the docosahexaenoic acid-derived resolvin D1 and maresin-1 were also elevated in HCDL individuals compared to HCNDL. Principal component analyses provided further evidence that lipid mediators could serve as an early biomarker for progression to active leprosy. A logistic model identified resolvin D1 and D2, and prostaglandin D as having the greatest potential for early detection of HCs that will manifest leprosy.
家庭内接触者（HCs）感染麻风病的风险增加，约 5-10%的 HCs 会发展为活动性疾病。一种预测工具，用于识别具有发展为活动性疾病最大风险的 HCs，将增强麻风病的早期诊断并优化预防性干预。先前的代谢组学研究表明，来源于 ω-3 和 ω-6 多不饱和脂肪酸（PUFA）的宿主脂质介质是麻风病的潜在生物标志物。在这项研究中，我们通过液相色谱-质谱和酶联免疫吸附法对麻风病 HCs 的回顾性血清进行了研究，以确定在发展为麻风病的 HCs（HCDL）与未发展为麻风病的 HCs（HCNDL）相比，循环 ω-3 和 ω-6 PUFA 代谢物水平是否发生改变。血清是在索引病例诊断时和麻风病临床症状/体征出现之前从 HCs 中收集的。我们的研究结果表明，与 HCNDL 相比，HCDL 血清表现出明显不同的代谢特征。具体而言，花生四烯酸、白三烯 B、11-羟基二十碳四烯酸、前列腺素 D 和脂氧素 A 在 HCDL 中升高。相比之下，HCDL 中的前列腺素 E 水平降低。与 HCNDL 相比，ω-3PUFA，二十二碳六烯酸、二十碳五烯酸以及二十二碳六烯酸衍生的分辨率 D1 和maresin-1 在 HCDL 个体中也升高。主成分分析提供了进一步的证据，表明脂质介质可以作为进展为活动性麻风病的早期生物标志物。逻辑回归模型确定分辨率 D1 和 D2 以及前列腺素 D 具有最大的潜力，可用于早期检测将表现出麻风病的 HCs。
