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Proc Natl Acad Sci U S A. 2016 Dec 20;113(51):E8277-E8285. doi: 10.1073/pnas.1618300114. Epub 2016 Dec 7.

Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency.

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Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, 75015 Paris, France.
Imagine Institute, Paris Descartes University, 75015 Paris, France.
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065.
Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, 734-8551, Japan.
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195.
Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, 80337 Munich, Germany.
Institute for Research and Medical Consultation, University of Dammam, Dammam 31441, Saudi Arabia.
Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Erciyes University, 38030 Kayseri, Turkey.
Department of Dermatology, Necker Hospital for Sick Children, 75015 Paris, France.
Center of Bone Marrow Transplantation, Faculty of Medicine, University of the Ryukyus, Okinawa 903-0213, Japan.
Division of Infectious Diseases, Clinical Immunology and Allergy, Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University, 34452 Istanbul, Turkey.
Department of Immunology and Rheumatology, Juan P. Garrahan National Pediatric Hospital, C1245AAM Buenos Aires, Argentina.
Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, 06100 Ankara, Turkey.
Department of Technology Development, Kazusa DNA Research Institute, Chiba 292-0818, Japan.
Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, 75015 Paris, France.
Department of Immunology, Hospital Del Niño Jesus, 4000 San Miguel de Tucumán, Tucumán, Argentina.
Department of Pediatric Immunology, Dr. Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, 06080 Ankara, Turkey.
Department of Dermatology, Algiers Faculty of Medicine, University of Algiers, Algiers 16030, Algeria.
Prince Naif Center for Immunology Research, King Saud University, Riyadh 12372, Saudi Arabia.
Department of General Pediatrics and Pediatric Infectious Diseases, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, 75015 Paris, France.
Department of Pediatric Immunology and Allergy, Antalya Education and Research Hospital, 07070 Antalya, Turkey.
Department of Pediatrics, College of Medicine, King Fahad Hospital of the University, University of Dammam, Al-Khobar 31952, Saudi Arabia.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR 1163, 75015 Paris, France;
Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France.
Howard Hughes Medical Institute, New York, NY 10065.


Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.


candidiasis; genetics; immunodeficiency

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