A HomozygousCARD9Mutation in a Family with Susceptibility to Fungal Infections

Abstract

BACKGROUND-Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant inheritance and autosomal recessive inheritance have been described.

Severe infectious diseases of childhood as monogenic inborn errors of immunity

“…All patients tested carried biallelic mutations of the gene encoding caspase recruitment domain family member 9 (CARD9) (80). Deficiency of this intracellular molecule had previously been identified in a large kindred with invasive and peripheral candidiasis (81). These studies led to the determination of the genetic basis of other invasive fungal infections.…”

The role of pattern recognition receptors in the innate recognition ofCandida albicans

“…Patients with deficiency in Th17-mediated adaptive immunity frequently suffer from chronic mucocutaneous candidiasis. [167][168][169][170][171] …”

“…More specifically, gal3-/-mice died significantly faster and exhibited a trend toward increased fungal burden and increased abscess formation in infected brains compared to WT mice. 186 [198,170] NLRP3 has been found critical for the control of C. albicans infections. 35 Mice deficient in NLRP3 displayed diminished serum IL-1b, reduced survival and higher fungal burdens in kidney, spleen, liver, and lung upon C. albicans infection.…”

“…198 After performing genetic studies on a family with susceptibility to fungal infections, a homozygous Q295X mutation in CARD9 is associated with susceptibility to chronic mucocutaneous candidiasis. 170 These studies indicate that PRRs are actively involved in antifungal response in humans, and the roles of PRRs in humans and mice are different. There is no doubt that TLR2 is essential in defense against C. albicans in mice.…”

The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous Candidiasis in Humans

“…We believe that multiple cell-fungal interactions may be required to initiate and mount predominantly Th17 differentiation and the relative role of various PRRs in this complex immunopathological process should be the focus of further research. For example, primary deficiency of caspase recruitment domain (CARD) 9 involved in signaling by different lectin receptors was described in a large Iranian family and was proposed to predispose patients to CMC [55]. However, two of the eight patients reported in this family also had invasive candidiasis and two of the patients had no proven candidal disease.…”