Sousa A O, Salem J I, Lee F K, Verçosa M C, Cruaud P, Bloom B R, Lagrange P H, David H L
Unité de la Tuberculose et des Mycobactéries, Institut Pasteur, Paris, France.
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13227-32. doi: 10.1073/pnas.94.24.13227.
A survey of an emerging tuberculosis epidemic among the Yanomami Indians of the Amazonian rain forest provided a unique opportunity to study the impact of tuberculosis on a population isolated from contact with the tubercle bacillus for millennia until the mid-1960s. Within the Yanomami population, an extraordinary high prevalence of active tuberculosis (6.4% of 625 individuals clinically examined) was observed, indicating a high susceptibility to disease, even among bacille Calmette-Guérin-vaccinated individuals. Observational studies on cell-mediated and humoral immune responses of the Yanomami Indians compared with contemporary residents of the region suggest profound differences in immunological responsiveness to Mycobacterium tuberculosis infection. Among the Yanomami, a very high prevalence of tuberculin skin test anergy was found. Of patients with active tuberculosis, 46% had purified protein derivative of tuberculosis reactions <10 mm; similarly 58% of recent bacillus Calmette-Guérin vaccines exhibited skin test reactions <5 mm. The Yanomami also had higher titers of antibodies against M. tuberculosis glycolipid antigens (>70%) than the control subjects comprised of Brazilians of European descent (14%). The antibodies were mostly of the IgM isotype. Among the tuberculosis patients who also produced IgG antibodies, the titers of IgG4 were significantly higher among the Yanomami than in the control population. Although it was not possible to analyze T-cell responses or patterns of lymphokine production in vitro because of the remoteness of the villages from laboratory facilities, the results suggest that the first encounter of the Yanomami Indian population with tuberculosis engenders a diminished cell-mediated immune response and an increased production antibody responses, relative to other populations with extensive previous contact with the pathogen. These findings suggest that tuberculosis may represent a powerful selective pressure on human evolution that over centuries has shaped the nature of human immune responses to infection.
对亚马逊雨林雅诺马马印第安人中出现的结核病疫情进行的一项调查，提供了一个独特的机会，来研究结核病对一个数千年来一直与世隔绝、直到20世纪60年代中期才接触结核杆菌的人群的影响。在雅诺马马人群中，观察到活动性结核病的患病率极高（在625名接受临床检查的个体中占6.4%），这表明即使在接种卡介苗的个体中，对该病的易感性也很高。与该地区当代居民相比，对雅诺马马印第安人的细胞介导免疫反应和体液免疫反应进行的观察性研究表明，对结核分枝杆菌感染的免疫反应存在深刻差异。在雅诺马马人中，发现结核菌素皮肤试验无反应的患病率非常高。在活动性结核病患者中，46%的人结核菌素纯蛋白衍生物反应<10毫米；同样，58%的近期卡介苗接种者皮肤试验反应<5毫米。雅诺马马人针对结核分枝杆菌糖脂抗原的抗体滴度也高于由欧洲血统的巴西人组成的对照组（>70%对14%）。这些抗体大多是IgM同种型。在也产生IgG抗体的结核病患者中，雅诺马马人的IgG4滴度明显高于对照人群。尽管由于村庄距实验室设施较远，无法在体外分析T细胞反应或淋巴因子产生模式，但结果表明，与其他此前广泛接触该病原体的人群相比，雅诺马马印第安人群首次接触结核病时，细胞介导的免疫反应减弱，抗体反应增强。这些发现表明，结核病可能是人类进化过程中的一种强大选择压力，几个世纪以来塑造了人类对感染的免疫反应性质。
