Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
J Clin Invest. 2012 May;122(5):1596-7. doi: 10.1172/jci62990.
Pediatricians first described the clinical features of chronic granulomatous disease (CGD) in 1959. Almost a decade later, in a collaborative effort that crossed disciplines, we participated in the discoveries that defined the cellular deficiencies of CGD, specifically finding that improper degranulation of leukocytes did not explain their failure to fight pathogens, rather that the fundamental defect was due to problems in the unique NADPH oxidase system of phagocytizing leukocytes. In the years that followed, the subunit components and structure of NADPH oxidase and their translocation during leukocyte phagocytosis to form the active enzyme were well described, leading to the identification of the component genes, the mapping of their chromosomal locations, and their subsequent cloning. This remarkable progress has led to effective therapies, including bone marrow transplants and gene therapy, that would have been unimaginable when we began.
儿科医生于 1959 年首次描述了慢性肉芽肿病（CGD）的临床特征。几乎十年后，我们在跨学科的合作中参与了定义 CGD 细胞缺陷的发现，特别是发现白细胞的不当脱颗粒并不能解释它们无法对抗病原体，而是由于吞噬白细胞的独特 NADPH 氧化酶系统存在问题导致了基本缺陷。在随后的几年中，NADPH 氧化酶的亚基成分和结构及其在白细胞吞噬作用过程中的转位以形成活性酶的过程得到了很好的描述，从而导致了对组成基因的鉴定、染色体位置的定位以及随后的克隆。这一显著进展带来了有效的治疗方法，包括骨髓移植和基因治疗，这在我们开始时是难以想象的。
