Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species–induced meningoencephalitis, colitis, or both
- Type de publi. : Article dans une revue
- Date de publi. : 01/06/2015
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Auteurs :
Fanny LanternierSeyed Alireza MahdavianiElisa BarbatiHélène ChaussadeYatrika KoumarRomain LevyBlandine DenisAnne-Sophie BrunelSophie MartinMichele LoopJulie PeetersAriel de SelysJean VanclaireChristiane VermylenMarie-Cécile NassogneOlga ChatzisLuyan LiuMelanie MigaudVincent PedergnanaGuillaume DesoubeauxGrégory JouvionFabrice ChretienIlad Alavi DarazamAlejandro SchäfferMihai G. NeteaJean de BruyckerLouis BernardJacques ReynesNoureddine AmazrineLaurent AbelDimitri van Der LindenTom HarrisonCapucine PicardOlivier LortholaryNico MarrJean‐laurent CasanovaAnne Puel
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Organismes :
Imagine - Institut des maladies génétiques
Centre d'infectiologie Necker-Pasteur [CHU Necker]
Université Paris Descartes - Paris 5
Shahid Beheshti University
Imagine - Institut des maladies génétiques
Université Paris Descartes - Paris 5
Centre Hospitalier Régional Universitaire de Tours
Hôpital Bretonneau
Centre Hospitalier Universitaire de Nîmes
Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France
Université de Montpellier
Imagine - Institut des maladies génétiques
Université Paris Descartes - Paris 5
Imagine - Institut des maladies génétiques
Centre d'infectiologie Necker-Pasteur [CHU Necker]
Université Paris Descartes - Paris 5
Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France
Cliniques Universitaires Saint-Luc [Bruxelles]
Clinique Saint-Jean [Bruxelles]
Université Catholique de Louvain = Catholic University of Louvain
Clinique Saint-Jean [Bruxelles]
Clinique Saint-Jean [Bruxelles]
Cliniques Universitaires Saint-Luc [Bruxelles]
Cliniques Universitaires Saint-Luc [Bruxelles]
Cliniques Universitaires Saint-Luc [Bruxelles]
Imagine - Institut des maladies génétiques
Université Paris Descartes - Paris 5
Imagine - Institut des maladies génétiques
Université Paris Descartes - Paris 5
Imagine - Institut des maladies génétiques
Université Paris Descartes - Paris 5
Centre Hospitalier Régional Universitaire de Tours
Pathologies Respiratoires : Protéolyse et Aérosolthérapie
Histopathologie humaine et Modèles animaux
Histopathologie humaine et Modèles animaux
Centre Hospitalier Sainte Anne [Paris]
Shahid Beheshti University
National Institutes of Health [Bethesda, MD, USA]
Radboud University Medical Center [Nijmegen]
Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada]
Centre Hospitalier Régional Universitaire de Tours
Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France
Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes
Imagine - Institut des maladies génétiques
Université Paris Descartes - Paris 5
Cliniques Universitaires Saint-Luc [Bruxelles]
St George's, University of London
Imagine - Institut des maladies génétiques
Service d'immuno-hématologie pédiatrique [CHU Necker]
Université Paris Descartes - Paris 5
Imagine - Institut des maladies génétiques
Centre d'infectiologie Necker-Pasteur [CHU Necker]
Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals
Shahid Beheshti University
Imagine - Institut des maladies génétiques
Service d'immuno-hématologie pédiatrique [CHU Necker]
Université Paris Descartes - Paris 5
Imagine - Institut des maladies génétiques
Université Paris Descartes - Paris 5
- Publié dans Journal of Allergy and Clinical Immunology le 31/10/2020
Résumé : BACKGROUND: Invasive infections of the central nervous system (CNS) or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningoencephalitis, colitis, or both caused by Candida species remain unexplained. OBJECTIVE: We studied 5 previously healthy children and adults with unexplained invasive disease of the CNS, digestive tract, or both caused by Candida species. The patients were aged 39, 7, 17, 37, and 26 years at the time of infection and were unrelated, but each was born to consanguineous parents of Turkish (2 patients), Iranian, Moroccan, or Pakistani origin. Meningoencephalitis was reported in 3 patients, meningoencephalitis associated with colitis was reported in a fourth patient, and the fifth patient had colitis only. METHODS: Inherited caspase recruitment domain family, member 9 (CARD9) deficiency was recently reported in otherwise healthy patients with other forms of severe disease caused by Candida, Trichophyton, Phialophora, and Exophiala species, including meningoencephalitis but not colitis caused by Candida and Exophiala species. Therefore we sequenced CARD9 in the 5 patients. RESULTS: All patients were found to be homozygous for rare and deleterious mutant CARD9 alleles: R70W and Q289* for the 3 patients with Candida albicans-induced meningoencephalitis, R35Q for the patient with meningoencephalitis and colitis caused by Candida glabrata, and Q295* for the patient with Candida albicans-induced colitis. Regardless of their levels of mutant CARD9 protein, the patients' monocyte-derived dendritic cells responded poorly to CARD9-dependent fungal agonists (curdlan, heat-killed C albicans, Saccharomyces cerevisiae, and Exophiala dermatitidis). CONCLUSION: Invasive infections of the CNS or digestive tract caused by Candida species in previously healthy children and even adults might be caused by inherited CARD9 deficiency.
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