%0 Case Reports
%T A novel inherited CARD9 deficiency in an otherwise healthy woman with CNS candidiasis.
%A Zhou LH
%A Qiu WJ
%A Que CX
%A Cheng JH
%A Zhu RS
%A Huang JT
%A Jiang YK
%A Zhao HZ
%A Wang X
%A Cheng XJ
%A Zhu LP
%J Clin Immunol
%V 265
%N 0
%D 2024 Aug 25
%M 38936523
%F 10.19
%R 10.1016/j.clim.2024.110293
%X Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.