aLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980 Necker Medical School, Imagine Institute and Paris Descartes University, Sorbonne Paris Cité bInfectious Diseases and Tropical Medicine Unit, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University cPasteur Institute, National Reference Center of Invasive Mycoses and Antifungals, Paris, France dSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA eStudy Center for Immunodeficiency fPediatric Hematology-Immunology Unit, Necker Enfants-Malades Hospital, AP-HP, and Paris Descartes University, Sorbonne Paris Cité, Paris, France.
Curr Opin Pediatr. 2013 Dec;25(6):736-47. doi: 10.1097/MOP.0000000000000031.
We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors.
An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-γ immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis.
CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases.
我们综述了导致各种浅部和深部真菌感染的原发性免疫缺陷病（PID）。我们还强调，此类真菌感染的发生应促使医生寻找相应的单一基因遗传性免疫缺陷。最后，我们认为，其他真菌感染也可能是由目前尚不清楚的遗传性免疫缺陷引起的，至少在一些无已知危险因素的患者中是如此。
越来越多的 PID 被证实与儿童和青年成人的真菌感染性疾病有关。吞噬细胞 NADPH 氧化酶复合物（慢性肉芽肿病）、严重先天性中性粒细胞减少症（SCN）和白细胞黏附缺陷 I 型的遗传性缺陷易导致侵袭性曲霉病和念珠菌病。较少见的是，干扰素-γ免疫遗传性缺陷导致地方性真菌病。最近发现白细胞介素-17 免疫遗传性缺陷可导致慢性黏膜皮肤念珠菌病（CMC），而半胱天冬酶募集域蛋白 9（CARD9）免疫遗传性缺陷可导致深部皮肤癣菌病和侵袭性念珠菌病。
CMC、侵袭性念珠菌病、侵袭性曲霉病、深部皮肤癣菌病、肺孢子菌病和地方性真菌病均可由 PID 引起。每种类型的感染都高度提示存在特定类型的 PID。在无明显危险因素的情况下，儿童和青年成人发生这些和其他真菌感染时，应寻找单一基因遗传性免疫缺陷。
