A novel inherited CARD9 deficiency in an otherwise healthy woman with CNS candidiasis

Clin Immunol. 2024 Aug:265:110293. doi: 10.1016/j.clim.2024.110293. Epub 2024 Jun 25.


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.

Keywords: CARD9; CNS; Candidiasis; Monocyte; Primary immunodeficiency.

Publication types

  • Case Reports

MeSH terms

  • CARD Signaling Adaptor Proteins* / deficiency
  • CARD Signaling Adaptor Proteins* / genetics
  • Candidiasis, Chronic Mucocutaneous / genetics
  • Candidiasis, Chronic Mucocutaneous / immunology
  • Cytokines
  • Female
  • Humans
  • Monocytes / immunology
  • Mutation
  • Neutrophils / immunology
  • Th17 Cells / immunology
  • Young Adult


  • CARD Signaling Adaptor Proteins
  • CARD9 protein, human
  • Cytokines

Supplementary concepts

  • Candidiasis familial chronic mucocutaneous, autosomal recessive