Immune deficiencies, infection, and systemic immune disordersInherited CARD9 deficiency in otherwise healthy children and adults with Candida species–induced meningoencephalitis, colitis, or both
Section snippets
Methods
Details of the materials and methods used in this study are provided in the Methods section in this article's Online Repository at www.jacionline.org.
Case reports
We describe 5 patients with proved Candida species infections of the CNS, the digestive tract, or both from 5 unrelated consanguineous families originating from Turkey (n = 2), Iran Morocco, and Pakistan (n = 1 each, Table I).
Kindred A
A 42-year-old woman (P1, A.II.2; Fig 1, A) living in France and born to consanguineous Turkish parents presented at 39 years of age with Candida albicans–induced meningitis and brain abscesses. She had recurrent vulvovaginal candidiasis, with episodes occurring about 5
Discussion
Four of the 5 patients described here displayed Candida species infections of the CNS, one of which was associated with Candida species–induced colitis, whereas the fifth patient had Candida species–induced colitis solely. Our findings demonstrate that CARD9 deficiency is a genetic cause of rare forms of invasive candidiasis and that CARD9 plays an essential role against Candida species infection in the brain and colon. This is concordant with the recently reported role of Card9 in mouse
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Cited by (0)
Supported in part by the Rockefeller University, INSERM, Paris Descartes University, the St. Giles Foundation and l'Agence Nationale de la Recherche (grant GENCMCD no 11-BSV3-005-01 to A.P.), and a Translational Research grant from the Jeffrey Modell Foundation (to A.P.). This study also received funding from the French Government as part of the Investissement d'Avenir program, Laboratoire d'Excellence “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID). F.L. was supported by a grant from the CMIT (French Faculties College of Infectious Diseases) and INSERM.
Disclosure of potential conflict of interest: F. Lanternier has received payment for lectures and travel support from Gilead Science, Novartis, and MSD. B. Denis has received payment for lectures from Gilead and has received travel support from Jansen. A.-S. Brunel is employed by the University of Montpellier and the Hospital of Montpellier. G. Desoubeaux has consultant arrangements with the Agence National de Sécurité du Médicament and has received travel support from MSD and Pfizer. A. A. Schäffer is employed by the National Institutes of Health. J. Reynes is a board member for and has received payment for development of educational presentations and travel support from Abbvie, Gilead, MSD, Pfizer, Tibotec-Janssen, and ViiV Healthcare; has consultant arrangements with Splicos Start Up; is employed by University of Montpellier and Hospital of Montpellier. L. Abel has received research support from l'Agence Nationale de la Recherche (GENCMCD 11-BSV3-005-01) and Laboratoire d'Excellence “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID). D. Van der Linden is a member of Conseil Supérieur de la Santé; is employed by Cliniques universitaires Saint-Luc, Brussels, and Université de Namur; has received research support from Abbvie; has received payment for lectures from Nutricia; and has received travel support from GlaxoSmithKline and Gilead. O. Lortholary has a board membership with Merck Sharp & Dohme; has consultant arrangements with Gilead; and has received payment for lectures from Astellas, Gilead, Merck/Schering, and Pfizer. J.-L. Casanova has received research support from the National Institutes of Health (grant no. 8UL1TR000043 from the National Center for Research Resources and the National Center for Advancing Translational Sciences [NCATS]) and has consultant arrangements with Merck, Regeneron, Bioaster, Pfizer, Biogen Idec, and Sanofi-Aventis. A. Puel has received research support from l'Agence Nationale de la Recherche (grant GENCMCD no. 11-BSV3-005-01) and the Jeffrey Modell Foundation. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.