PURPOSE Caspase-associated recruitment domain-9 (CARD9) deficiency is an inborn error of immunity that typically predisposes otherwise healthy patients to single fungal infections and the occurrence of multiple invasive fungal infections is rare. It has been described as the first known condition that predisposes to extrapulmonary Aspergillus infection with preserved lungs. We present a patient that expands the clinical variability of CARD9 deficiency. MATERIALS AND METHODS Genetic analysis was performed by Sanger sequencing. Neutrophils and mononuclear phagocyte response to fungal stimulation were evaluated through luminol-enhanced chemiluminescence and whole blood production of the proinflammatory mediator interleukin (IL)-6, respectively. RESULTS We report a 56-year-old Argentinean woman, whose invasive Exophiala spinifera infection at the age of 32 years was unexplained and reported in year 2004. At the age of 49 years, she presented with chronic pulmonary disease due to Aspergillus nomius. After partial improvement following treatment with caspofungin and posaconazole, right pulmonary bilobectomy was performed. Despite administration of multiple courses of antifungals, sustained clinical remission could not be achieved. We recently found that the patient's blood showed an impaired production of IL-6 when stimulated with zymosan. We also found that she is homozygous for a previously reported CARD9 loss-of-function mutation (Q289*). CONCLUSIONS This is the first report of a patient with inherited CARD9 deficiency and chronic invasive pulmonary aspergillosis (IPA) due to A. nomius. Inherited CARD9 deficiency should be considered in otherwise healthy children and adults with one or more invasive fungal diseases.

中文翻译：

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患有 Exophiala spinifera 和 Aspergillus nomius 严重感染的患者的遗传性 CARD9 缺陷。

目的 Caspase 相关募集域 9 (CARD9) 缺陷是一种先天性免疫错误，通常会使原本健康的患者易患单一真菌感染，并且很少发生多种侵袭性真菌感染。它已被描述为第一个已知的易患肺外曲霉菌感染且保留的肺的疾病。我们介绍了一名患者，该患者扩大了 CARD9 缺乏症的临床变异性。材料与方法通过Sanger测序进行遗传分析。中性粒细胞和单核吞噬细胞对真菌刺激的反应分别通过鲁米诺增强的化学发光和全血产生的促炎介质白细胞介素 (IL)-6 进行评估。结果 我们报告了一名 56 岁的阿根廷妇女，2004 年，她在 32 岁的时候感染了 Exophiala spinifera 感染，原因不明。她在 49 岁的时候出现了由白曲霉引起的慢性肺部疾病。在用卡泊芬净和泊沙康唑治疗后部分改善后，进行了右肺双叶切除术。尽管施用了多个疗程的抗真菌药，但仍无法实现持续的临床缓解。我们最近发现，当用酵母聚糖刺激时，患者的血液显示出 IL-6 的产生受损。我们还发现她是先前报道的 CARD9 功能丧失突变 (Q289*) 的纯合子。结论 这是第一份关于遗传性 CARD9 缺陷和慢性侵袭性肺曲霉病 (IPA) 患者的报告。