Ling Y, Puel A
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM 1163, Paris, France; Imagine Institute, University Paris Descartes, Paris, France.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM 1163, Paris, France; Imagine Institute, University Paris Descartes, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New York, NY, USA.
Actas Dermosifiliogr. 2014 Oct;105 Suppl 1:34-40. doi: 10.1016/S0001-7310(14)70016-X.
IL-17 immunity has been shown to be essential for mucocutaneous protection against Candida albicans in mice and humans. However, mice with defective IL-17 immunity display broader susceptibility, as they are also prone to infections with diverse infectious agents at various sites. Humans with genetic defects affecting their IL-17 immunity usually suffer from chronic mucocutaneous candidiasis (CMC): recurrent or persistent infections of the skin, nails, and mucosae with C. albicans, with or without other clinical signs. Most patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) due to STAT3 deficiency or AD STAT1 gain-of-function display impaired IL-17-producing T-cell development, and CMC is one of their principal clinical manifestations. Similarly, patients with autosomal recessive (AR) autoimmune polyendocrine syndrome type 1 (APS-1) caused by AIRE deficiency have high levels of neutralizing autoantibodies against IL-17A, IL-17F and/or IL-22 and present CMC as their only infectious disease. Finally, CMC is the main clinical phenotype observed in patients with inborn errors specifically affecting IL-17 immunity. Indeed, patients with AD IL-17F deficiency or AR IL-17RA or ACT1 deficiency display CMC and, to a lesser extent, superficial staphylococcal diseases. Candida infection was recently reported in psoriasis patients treated with anti-IL-17A antibodies. Careful monitoring for CMC is thus important during anti-IL-17 treatment.
白细胞介素-17免疫已被证明对小鼠和人类黏膜皮肤抵抗白色念珠菌的保护至关重要。然而，白细胞介素-17免疫缺陷的小鼠易感性更高，因为它们在各个部位也容易感染多种病原体。影响白细胞介素-17免疫的基因缺陷的人类通常患有慢性黏膜皮肤念珠菌病（CMC）：皮肤、指甲和黏膜反复或持续感染白色念珠菌，伴有或不伴有其他临床症状。大多数因信号转导子和转录激活子3（STAT3）缺陷或常染色体显性（AD）STAT1功能获得导致的常染色体显性（AD）高免疫球蛋白E综合征（HIES）患者，其产生白细胞介素-17的T细胞发育受损，CMC是其主要临床表现之一。同样，由自身免疫调节因子（AIRE）缺陷引起的常染色体隐性（AR）自身免疫性多内分泌综合征1型（APS-1）患者，针对白细胞介素-17A、白细胞介素-17F和/或白细胞介素-22的中和自身抗体水平较高，且CMC是其唯一的传染病。最后，CMC是在先天性错误中特别影响白细胞介素-17免疫的患者中观察到的主要临床表型。事实上，常染色体显性白细胞介素-17F缺陷或常染色体隐性白细胞介素-17受体A（IL-17RA）或激活子1（ACT1）缺陷的患者表现出CMC，程度较轻的还有浅表葡萄球菌疾病。最近有报道称，接受抗白细胞介素-17A抗体治疗的银屑病患者出现念珠菌感染。因此，在抗白细胞介素-17治疗期间，仔细监测CMC很重要。
