Segal Brahm H, Romani Luigina R
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Med Mycol. 2009;47 Suppl 1:S282-90. doi: 10.1080/13693780902736620. Epub 2009 Mar 18.
Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase complex in which phagocytes are defective in generating superoxide anion and its metabolites. NADPH oxidase activation leads to activation of sequestered neutrophil proteases that mediate host defense. Invasive aspergillosis and other rarer mold diseases are the leading causes of mortality in CGD, reflecting the key role of the phagocyte NADPH oxidase in host defense against opportunistic fungi. Despite recombinant interferon-gamma prophylaxis, invasive filamentous fungal infections are a persistent problem in CGD. Key principles of management of fungal infections involve early recognition and aggressive treatment and appropriate surgical debridement of localized disease. Because CGD is a disorder of phagocyte stem cells in which the gene defects are well defined, it is a model disease to evaluate immune reconstitution through stem cell transplantation and gene therapy. Recent studies using CGD mice show that defects in tryptophan catabolism may underlie the impaired host defense and pathogenic inflammation in CGD and open the potential for novel therapeutic approaches; however, correlative studies in patients are required.
慢性肉芽肿病（CGD）是一种NADPH氧化酶复合物的遗传性疾病，其中吞噬细胞在产生超氧阴离子及其代谢产物方面存在缺陷。NADPH氧化酶激活导致隔离的中性粒细胞蛋白酶激活，从而介导宿主防御。侵袭性曲霉病和其他较罕见的霉菌病是CGD患者死亡的主要原因，这反映了吞噬细胞NADPH氧化酶在宿主抵御机会性真菌中的关键作用。尽管使用重组干扰素-γ进行预防，但侵袭性丝状真菌感染仍是CGD中持续存在的问题。真菌感染管理的关键原则包括早期识别、积极治疗以及对局部疾病进行适当的手术清创。由于CGD是一种吞噬细胞干细胞疾病，其基因缺陷已明确，因此它是通过干细胞移植和基因疗法评估免疫重建的模型疾病。最近使用CGD小鼠的研究表明，色氨酸分解代谢缺陷可能是CGD中宿主防御受损和致病性炎症的基础，并为新的治疗方法开辟了潜力；然而，需要在患者中进行相关性研究。
