León-Lara Ximena, Rodríguez-D'Cid Roberto, Rioja-Valencia Ricardo, Ayala-Alvirde Alexandra, Aliaga-Taipe Ida Lizbeth, Espinosa-Padilla Sara, Blancas-Galicia Lizbeth
Secretaría de Salud, Instituto Nacional de Pediatría, Unidad de Investigación en Inmunodeficiencias, Ciudad de México, México.
Rev Alerg Mex. 2020 Oct-Dec;67(4):370-380. doi: 10.29262/ram.v67i4.784.
Chronic granulomatous disease (CGD) is an inborn error of immunity. CGD is characterized by a deficiency in the function of the NADPH oxidase complex. CGD has been an opportunity to study the function of reactive oxygen species (ROS) in the innate immune system. The absence of ROS produced by NADPH oxidase in neutrophils and macrophages leads to an increased susceptibility to bacterial and fungal infections since ROS participate in the elimination of microorganisms. Inflammatory and autoimmune manifestations are also present in CGD; however, the causal connection between the lack of ROS and inflammatory symptoms is not entirely clear. Different in vitro assays have been conducted in humans and clinical trials have been conducted in mice in order to try to understand this relationship. Studies show that ROS react with different molecules of the immune system, either by inhibiting or by stimulating their function, which explains why various inflammation pathways that are not related to each other are affected in CGD; therefore, the described mechanisms of affectation have been diverse, such as a greater production of proinflammatory cytokines, an increase in TH17 lymphocytes, and an alteration in processes like spherocytosis, apoptosis, autophagy, and inflammosome. Understanding the mechanisms that lead to inflammation in the deficiency of the NADPH oxidase complex has led to the proposal of new treatments that act on processes like autophagy, inflammosome, or blocking proinflammatory cytokines. In this review, we describe the different inflammatory manifestations in CGD and the molecular mechanisms through which the lack of ROS leads to hyperinflammation.
慢性肉芽肿病（CGD）是一种先天性免疫缺陷病。CGD的特征是NADPH氧化酶复合物功能缺陷。CGD为研究活性氧（ROS）在先天免疫系统中的功能提供了契机。中性粒细胞和巨噬细胞中NADPH氧化酶产生的ROS缺失导致对细菌和真菌感染的易感性增加，因为ROS参与微生物的清除。CGD中也存在炎症和自身免疫表现；然而，ROS缺乏与炎症症状之间的因果关系尚不完全清楚。为了试图理解这种关系，已在人体中进行了不同的体外试验，并在小鼠中进行了临床试验。研究表明，ROS与免疫系统的不同分子相互作用，通过抑制或刺激其功能来实现，这解释了为什么在CGD中互不相关的各种炎症途径会受到影响；因此，所描述的影响机制多种多样，如促炎细胞因子产生增加、TH17淋巴细胞增多以及红细胞异形症、凋亡、自噬和炎性小体等过程发生改变。了解导致NADPH氧化酶复合物缺乏时炎症发生的机制，促使人们提出了作用于自噬、炎性小体或阻断促炎细胞因子等过程的新治疗方法。在本综述中，我们描述了CGD中的不同炎症表现以及ROS缺乏导致炎症反应过度的分子机制。
