Dept. of Infectious Diseases, LUMC, PO Box 9600, 2300 RC Leiden, The Netherlands.
Semin Immunol. 2018 Oct;39:111-118. doi: 10.1016/j.smim.2018.06.003. Epub 2018 Jun 24.
Leprosy is still a considerable health threat in pockets of several low and middle income countries worldwide where intense transmission is witnessed, and often results in irreversible disabilities and deformities due to delayed- or misdiagnosis. Early detection of leprosy represents a substantial hurdle in present-day leprosy health care. The dearth of timely diagnosis has, however, particularly severe consequences in the case of inflammatory episodes, designated leprosy reactions, which represent the major cause of leprosy-associated irreversible neuropathy. There is currently no accurate, routine diagnostic test to reliably detect leprosy reactions, or to predict which patients will develop these immunological exacerbations. Identification of host biomarkers for leprosy reactions, particularly if correlating with early onset prior to development of clinical symptoms, will allow timely interventions that contribute to decreased morbidity. Development of a point-of-care (POC) test based on such correlates would be a definite game changer in leprosy health care. In this review, proteomic-, transcriptomic and metabolomic research strategies aiming at identification of host biomarker-based correlates of leprosy reactions are discussed, next to external factors associated with occurrence of these episodes. The vast diversity in research strategies combined with the variability in patient- and control cohorts argues for harmonisation of biomarker discovery studies with geographically overarching study sites. This will improve identification of specific correlates associated with risk of these damaging inflammatory episodes in leprosy and subsequent application to rapid field tests.
麻风病在全球一些低收入和中等收入国家仍然是一个相当大的健康威胁,这些国家存在高强度的传播,并且由于诊断延迟或误诊,往往导致不可逆转的残疾和畸形。麻风病的早期发现是当今麻风病保健的一个重大障碍。然而,在炎症发作(称为麻风反应)的情况下,及时诊断的缺乏尤其具有严重后果,因为这些反应是导致与麻风病相关的不可逆转神经病变的主要原因。目前没有准确、常规的诊断测试可以可靠地检测麻风反应,也无法预测哪些患者会出现这些免疫性恶化。确定麻风反应的宿主生物标志物,特别是如果与临床症状出现之前的早期发病相关联,将有助于及时干预,降低发病率。基于这些关联物开发即时护理点(POC)测试将是麻风病保健方面的一个重大改变。在这篇综述中,讨论了基于蛋白质组学、转录组学和代谢组学的研究策略,旨在确定与麻风反应相关的宿主生物标志物关联物,以及与这些发作相关的外部因素。研究策略的多样性与患者和对照组的可变性相结合,呼吁对生物标志物发现研究进行地理上的协调,以涵盖更广泛的研究地点。这将有助于识别与麻风病中这些破坏性炎症发作风险相关的具体关联物,并随后应用于快速现场测试。