Gaschignard J, Scurr E, Alcaïs A
Laboratoire de Génétique des Maladies Infectieuses, Institut national de la Santé et de la Recherche Médicale, U980, 156 rue de Vaugirard, 75015 Paris, France.
Pathol Biol (Paris). 2013 Jun;61(3):120-8. doi: 10.1016/j.patbio.2013.03.003. Epub 2013 May 24.
Despite a natural reservoir of Mycobacterium leprae limited to humans and free availability of an effective antibiotic treatment, more than 200,000 people develop leprosy each year. This disease remains a major cause of disability and social stigma worldwide. The cause of this constant incidence is currently unknown and indicates that important aspects of the complex relationship between the pathogen and its human host remain to be discovered. An important contribution of host genetics to susceptibility to leprosy has long been suggested to account for the considerable variability between individuals sustainably exposed to M. leprae. Given the inability to cultivate M. leprae in vitro and in the absence of relevant animal model, genetic epidemiology is the main strategy used to identify the genes and, consequently, the immunological pathways involved in protective immunity to M. leprae. Recent genome-wide studies have identified new pathophysiological pathways which importance is only beginning to be understood. In addition, the prism of human genetics placed leprosy at the crossroads of other common diseases such as Crohn's disease, asthma or myocardial infarction. Therefore, novel lights on the pathogenesis of many common diseases could eventually emerge from the detailed understanding of a disease of the shadows.
尽管麻风分枝杆菌的天然宿主仅限于人类，且有效抗生素治疗易于获取，但每年仍有超过20万人患上麻风病。在全球范围内，这种疾病仍然是导致残疾和社会耻辱的主要原因。目前尚不清楚这种持续发病率的原因，这表明病原体与其人类宿主之间复杂关系的重要方面仍有待发现。长期以来，人们一直认为宿主基因对麻风病易感性的重要贡献，可以解释持续接触麻风分枝杆菌的个体之间存在的显著差异。由于无法在体外培养麻风分枝杆菌，且缺乏相关动物模型，遗传流行病学是用于识别相关基因以及参与针对麻风分枝杆菌保护性免疫的免疫途径的主要策略。最近的全基因组研究已经确定了新的病理生理途径，其重要性才刚刚开始被理解。此外，人类遗传学视角将麻风病置于其他常见疾病（如克罗恩病、哮喘或心肌梗死）的交叉点上。因此，对许多常见疾病发病机制的新认识最终可能会从对这种“阴影疾病”的深入理解中浮现出来。
