CARD9 deficiency and spontaneous central nervous system candidiasis: complete clinical remission with GM-CSF therapy.
We demonstrate autosomal-recessive Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in a patient with relapsing C. albicans meningoencephalitis. We identified a novel, hypomorphic mutation with intact Th17 responses, but impaired GM-CSF responses. We report complete clinical remission with adjunctive GM-CSF therapy, suggesting that a CARD9/GM-CSF axis contributes to susceptibility to candidiasis.
Infectious Disease Susceptibility Program.
Christina
C
Gavino
Infectious Disease Susceptibility Program.
Anthony
A
Cotter
Infectious Disease Susceptibility Program.
Daniel
D
Lichtenstein
Department of Pediatrics, McGill University Health Centre, Montreal, Canada.
Duncan
D
Lejtenyi
Département de Microbiologie et Infectiologie, Centre Hospitalier de l'Université de Montréal, Canada.
Claude
C
Fortin
Department of Neurology and Neurosurgery, McGill University Health Centre, Montreal, Canada.
Catherine
C
Legault
Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal, Canada.
Najmeh
N
Alirezaie
Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, Montreal, Canada.
Jacek
J
Majewski
Department of Microbiology and Immunology, McGill University, Montreal, Canada.
Donald C
DC
Sheppard
Department of Medicine, Research Institute of the McGill University Health Centre, Montreal, Canada.
Marcel A
MA
Behr
Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Canada.
William D
WD
Foulkes
Infectious Disease Susceptibility Program.
Donald C
DC
Vinh
D000328:Adult; D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency*; D058365:Candidiasis, Invasive / Q000235:genetics*; D020314:Central Nervous System Fungal Infections / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D056747:Immunomodulation; D008297:Male; D016896:Treatment Outcome
D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D007155:Immunologic Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
CARD9; Candida; GM-CSF; Th17; spontaneous central nervous system candidiasis