CARD9 Deficiency and Other Syndromes of Susceptibility to Candidiasis

CARD9 deficiency is a genetic immune disorder characterized by susceptibility to fungal infections like candidiasis, which is caused by the yeast fungus Candida. Typically, Candida does not cause severe problems in healthy people, but it can take advantage of those with a weakened immune system.

NIAID researchers are exploring how mutations that cause Candida susceptibility impact the function of immune cells by studying people with genetic disorders such as CARD9 deficiency; SCID; and deficiencies in STAT1, STAT3 and DOCK8. NIAID researchers also are studying chronic mucocutaneous candidiasis (CMC) and systemic candidiasis—two types of Candida infection—in mouse models of these genetic disorders. By identifying the genetic defects responsible for a person’s immunodeficiency, researchers may be able to develop targeted therapies to prevent these opportunistic infections.

CARD9 deficiency, an autosomal recessive disorder, differs from many other genetic immune disorders that cause fungal infections. Most genetic immune disorders cause either CMC or systemic candidiasis, but people with CARD9 deficiency experience both CMC and systemic candidiasis. CMC is a localized Candida infection that causes lesions and scaling on the skin and nails. The infection also occurs in areas where the skin transitions to other tissues, such as the genital area, eyelids and mouth, and may progress along the throat. Normally, cells of the adaptive immune system, like T cells, stop this infection from taking hold. Systemic candidiasis is an invasive infection that involves the bloodstream and deep-seated organs such as the kidneys, brain, liver and/or spleen, and requires innate immune cells to prevent. CARD9 is required for anti-fungal responses in both innate and adaptive immune cells, explaining why people with this deficiency experience both conditions.

Systemic candidiasis may lead to life-threatening sepsis or meningitis, an infection of the brain and its linings. Many people with CARD9 deficiency develop systemic candidiasis that targets the central nervous system, or CNS. NIAID researchers have described the crucial role of CARD9 in recruiting infection-fighting neutrophils to the CNS during fungal infection, helping explain why people with CARD9 deficiency are highly susceptible to fungal CNS infections. 

Fungal infections are diagnosed by physical examination of the infected sites and by using laboratory tests to confirm the presence of Candida or other fungi. If warranted, genetic testing can confirm the presence of mutations associated with these infections, like CARD9 deficiency.

Patients with fungal infections may be prescribed antifungal medications.

To learn more about CARD9 deficiency and other syndromes of susceptibility to candidiasis, visit the National Library of Medicine, Genetics Home Reference familial candidiasis site.

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