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Chronic and Invasive Fungal Infections in a Family with CARD9 Deficiency

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An Erratum to this article was published on 26 April 2016

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.

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Acknowledgments

We thank Veronique Debacker for performing the immunofunctional assays.

Author information

Authors and Affiliations

  1. Department of Dermatology, Ghent University Hospital, Medical Research Building ground floor, De Pintelaan 185, 9000, Ghent, Belgium

    Ana Karina Alves de Medeiros, Evelyn Lodewick, Sara Bosma, Laure Vanderdonckt, Jo Lambert & Lieve Brochez

  2. Department of Pediatric Pulmonology and Immunology, Centre for Primary Immune deficiencies, Ghent University Hospital, Ghent, Belgium

    Delfien J. A. Bogaert, Filomeen Haerynck & Sabine Van daele

  3. Clinical Immunology Research Laboratory, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

    Delfien J. A. Bogaert, Filomeen Haerynck, Bart Lambrecht & Melissa Dullaers

  4. Laboratory for Mucosal Immunology, VIB Inflammation Research Center, Ghent, Belgium

    Bart Lambrecht & Melissa Dullaers

  5. Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium

    Bart Lambrecht

  6. Paris Descartes University, Imagine Institute, Paris, France

    Olivier Lortholary, Mélanie Migaud, Jean-Laurent Casanova, Anne Puel & Fanny Lanternier

  7. Infectious Diseases Unit, Necker-Enfants Malades Hospital, AP-HP Paris, Paris, France

    Olivier Lortholary & Fanny Lanternier

  8. Laboratory of Human Genetics of Infectious Diseases, Necker Branch; INSERM UMR1163, Necker Medical School, Paris, France

    Mélanie Migaud, Jean-Laurent Casanova, Anne Puel & Fanny Lanternier

  9. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA

    Jean-Laurent Casanova

  10. Pediatric Hematology-Immunology-Rheumatology Unit, AP-HP, Necker Enfants-Malades Hospital, Paris, France

    Jean-Laurent Casanova

  11. Howard Hughes Medical Institute, New York, NY, USA

    Jean-Laurent Casanova

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

Correspondence to Ana Karina Alves de Medeiros.

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Ana Karina Alves de Medeiros and Evelyn Lodewick authors contributed equally.

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Alves de Medeiros, A.K., Lodewick, E., Bogaert, D.J.A. et al. Chronic and Invasive Fungal Infections in a Family with CARD9 Deficiency. J Clin Immunol 36, 204–209 (2016). https://doi.org/10.1007/s10875-016-0255-8

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  • DOI: https://doi.org/10.1007/s10875-016-0255-8

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