ABSTRACT
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.
Subject(s)
Aspergillus/physiology , CARD Signaling Adaptor Proteins/genetics , Candidiasis, Chronic Mucocutaneous/diagnosis , Exophiala/physiology , Mutation/genetics , Phaeohyphomycosis/diagnosis , Pulmonary Aspergillosis/diagnosis , Candidiasis, Chronic Mucocutaneous/genetics , Cells, Cultured , Female , Humans , Interleukin-6/metabolism , Middle Aged , Pedigree , Phaeohyphomycosis/genetics , Pneumonectomy , Pulmonary Aspergillosis/geneticsABSTRACT
Several species of the genus Exophiala are found as opportunistic pathogens on humans, while others cause infections in cold-blooded waterborne vertebrates. Opportunism of these fungi thus is likely to be multifactorial. Ecological traits [thermotolerance and pH tolerance, laccase activity, assimilation of mineral oil, and decolorization of Remazol Brilliant Blue R (RBBR)] were studied in a set of 40 strains of mesophilic Exophiala species focused on the salmonis-clade mainly containing waterborne species. Thermophilic species and waterborne species outside the salmonis-clade were included for comparison. Strains were able to tolerate a wide range of pHs, although optimal growth was observed between pH 4.0 and 5.5. All strains tested were laccase positive. Strains were able to grow in the presence of the compounds (mineral oil and RBBR) with some differences in assimilation patterns between strains tested and also were capable of degrading the main chromophore of RBBR. The study revealed that distantly related mesophilic species behave similarly, and no particular trend in evolutionary adaptation was observed.