Immunodeficiency 51 B37.-; D81.8

Autosomal recessively inherited immunodeficiency caused by an interleukin-17 receptor A gene (IL17RA, 605461.0001) and characterized by a particular susceptibility to mucocutaneous candidiasis but also to staphylococcal infections.

Patients with CMCD show autosomal recessive IL17RA deficiency associated with a lack of cellular responses to the three IL17 cytokine dimers, IL17A (603149), IL17F (606496), and IL17A-IL17F, in fibroblasts and leukocytes (see below).

Onset in the first months of life.

Clinically, this immunodeficiency is characterized by:

• susceptibility to chronic mucocutaneous Candida infections
• susceptibility to skin infections caused by staphylococci
• Susceptibility to other bacterial infections (in some patients)
• Impaired cellular response to stimulation with certain IL17 isoforms.

Puel et al. (2011) studied a child (of Moroccan descent) who developed Candida albicans infection of the skin dermatitis and pyoderma with Staphylococcus aureus already in the neonatal period. Evidence included an autosomal recessive homozygous nonsense mutation in the IL17RA gene (605461.0001). The IL17RA protein was not detected on the surface of fibroblasts, peripheral blood monocytes, or CD4+ T cells, CD8+ T cells, or monocytes from the patient.

Levy et al (2016) reported 20 patients from 11 families with IMD51. The families had diverse ethnic origins, including Turkey, Japan, Saudi Arabia, Algeria, and Argentina, and most were consanguineous. All patients had chronic mucocutaneous candidiasis involving the scalp, mucosa, or nails before 6 months of age. Fourteen patients also had recurrent follicular pyoderma (staphylococci) at the same age. Eight children had other recurrent infections such as otitis, sinusitis, bronchitis, and lobar pneumonia. Detected were 11 different homozygous mutations in the IL17RA gene. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. There was a loss of IL17RA surface expression on fibroblasts and monocytes. Cells showed no responses to stimulation with specific IL17 isoforms, including IL17A, IL17F, IL17A/F, and IL17E. The results support the importance of IL17RA in mucocutaneous immunity.

1. Kudva A et al. (2011) Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice J Immun 186: 1666-1674.
2. Levy R et al (2016) Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency. Proc Nat Acad Sci 113: E8277-E8285.
3. Puel A et al (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332: 65-68.
4. Tan W et al. (2006) IL-17 receptor knockout mice have enhanced myelotoxicity and impaired hemopoietic recovery following gamma irradiation. J Immun 176: 6186-6193.