Chronic and Invasive Fungal Infections in a Family with CARD9 Deficiency

J Clin Immunol. 2016 Apr;36(3):204-9. doi: 10.1007/s10875-016-0255-8.

Ana Karina Alves de Medeiros ¹, Evelyn Lodewick ², Delfien J A Bogaert ³ ⁴, Filomeen Haerynck ³ ⁴, Sabine Van Daele ³, Bart Lambrecht ⁴ ⁵ ⁶, Sara Bosma ², Laure Vanderdonckt ², Olivier Lortholary ⁷ ⁸, Mélanie Migaud ⁷ ⁹, Jean-Laurent Casanova ⁷ ⁹ ¹⁰ ¹¹ ¹², Anne Puel ⁷ ⁹, Fanny Lanternier ⁷ ⁸ ⁹, Jo Lambert ², Lieve Brochez ², Melissa Dullaers ⁴ ⁵

Affiliations

1 Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium. ana.alvesdemedeiros@uzgent.be.
2 Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium.
3 Department of Pediatric Pulmonology and Immunology, Centre for Primary Immune deficiencies, Ghent University Hospital, Ghent, Belgium.
4 Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
5 Laboratory for Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium.
6 Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
7 Paris Descartes University, Imagine Institute, Paris, France.
8 Infectious Diseases Unit, Necker-Enfants Malades Hospital, AP-HP Paris, Paris, France.
9 Laboratory of Human Genetics of Infectious Diseases, Necker Branch; INSERM UMR1163, Necker Medical School, Paris, France.
10 St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
11 Pediatric Hematology-Immunology-Rheumatology Unit, AP-HP, Necker Enfants-Malades Hospital, Paris, France.
12 Howard Hughes Medical Institute, New York, NY, USA.

PMID: 26961233 DOI: 10.1007/s10875-016-0255-8

Abstract

Chronic mucocutaneous or invasive Fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive Fungal infections with Candida spp., dermatophytes (e.g., Trichophyton spp.) and phaeohyphomycetes (Exophiala spp., Phialophora verrucosa). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive Fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient. Two patients consented to genetic testing and were found to have a previously reported homozygous R70W CARD9 mutation. Circulating IL-17 and IL-22 producing T cells were decreased as was IL-6 and granulocyte/macrophage colony-stimulating factor (GM-CSF) secretion upon stimulation with Candida albicans. Patients with recurrent Fungal infections in the absence of known immunodeficiencies should be analyzed for CARD9 gene mutations as the cause of fungal Infection predisposition.

Keywords

Autosomal recessive CARD9 deficiency; Chronic mucocutaneous candidiasis; Cutaneous and deep dermatophytosis.

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