Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both

被引：144

作者：

Lanternier, Fanny ^{[1
,2
,3
]}

Mandaviani, Seyed Alireza ^{[4
]}

Barbati, Elisa ^{[1
,2
]}

Chaussade, Helene ^{[6
]}

Koumar, Yatrika ^{[7
]}

Levy, Romain ^{[1
,2
]}

Denis, Blandine ^{[2
,3
]}

Brunel, Anne-Sophie ^{[7
]}

Martin, Sophie ^{[8
]}

Loop, Michele ^{[11
]}

Peeters, Julie ^{[8
]}

de Selys, Ariel ^{[11
]}

Vanclaire, Jean ^{[11
]}

Vermylen, Christiane ^{[9
]}

Nassogne, Marie-Cecile ^{[10
]}

Chatzis, Olga ^{[8
]}

Liu, Luyan ^{[1
,2
]}

Migaud, Melanie ^{[1
,2
]}

Pedergnana, Vincent ^{[1
,2
]}

Desoubeaux, Guillaume ^{[12
]}

Jouvion, Gregory ^{[13
]}

Chretien, Fabrice ^{[13
,15
]}

Darazam, Ilad Alavi ^{[5
]}

Schaeffer, Alejandro A. ^{[16
]}

Netea, Mihai G. ^{[17
,18
]}

De Bruycker, Jean J. ^{[19
]}

Bernard, Louis ^{[6
]}

Reynes, Jacques ^{[7
]}

Amazrine, Noureddine ^{[20
]}

Abel, Laurent ^{[1
,2
,21
]}

Van der Linden, Dimitri ^{[8
]}

Harrison, Tom ^{[22
]}

Picard, Capucine ^{[1
,2
,23
,24
]}

Lortholary, Olivier ^{[2
,3
,14
]}

Mansouri, Davood ^{[5
]}

Casanova, Jean-Laurent ^{[1
,2
,21
,24
,25
]}

Puel, Anne ^{[1
,2
]}

机构：

[1] INSERM, UMR 1163, Lab Human Genet Infect Dis, Necker Branch, Paris, France

[2] Univ Paris 05, Imagine Inst, F-75015 Paris, France

[3] Hop Necker Enfants Malad, AP HP, Necker Pasteur Infect Dis Ctr, Imagine Inst, Paris, France

[4] NRITLD, Pediat Resp Dis Res Ctr, Tehran, Iran

[5] Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, Natl Res Inst TB & Lung Dis, Dept Clin Immunol & Allergy, Tehran, Iran

[6] Bretonneau Hosp, Infect Dis Unit, Tours, France

[7] Infect Dis Unit, Montpellier, France

[8] UCL, St Luc Univ Hosp, Pediat Infect Dis Unit, Brussels, Belgium

[9] UCL, St Luc Univ Hosp, Pediat Hematol Oncol Unit, Brussels, Belgium

[10] UCL, St Luc Univ Hosp, Pediat Neurol Unit, Brussels, Belgium

[11] St Jean Hosp, Pediat Neonatol Unit, Brussels, Belgium

[12] Bretonneau Hosp, Ctr Study Resp Dis, Parasitol Mycol Trop Med Unit, INSERM,U1100,Equipe 3,Sch Med, Tours, France

[13] Inst Pasteur, Human Histopathol & Anim Models, Infect & Epidemiol Dept, Paris, France

[14] Inst Pasteur, Mol Mycol Unit, Natl Reference Ctr Invas Mycoses & Antifungals, Paris, France

[15] Hop St Anne, Neuropathol Lab, F-75674 Paris, France

[16] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA

[17] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands

[18] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 ED Nijmegen, Netherlands

[19] Hop St Justine, Univ Ctr, Immunol & Rheumatol Unit, Montreal, PQ H3T 1C5, Canada

[20] Dept Neurosurg, Tangier, Morocco

[21] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10021 USA

[22] St Georges Univ London, Infect & Immun Res Inst, London, England

[23] Hop Necker Enfants Malad, AP HP, Study Ctr Immunodeficiency, Paris, France

[24] Hop Necker Enfants Malad, AP HP, Pediat Hematol Immunol Unit, Paris, France

[25] Howard Hughes Med Inst, New York, NY USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2015年 / 135卷 / 06期

关键词：

Inborn error of immunity; primary immunodeficiency; invasive fungal diseases; inherited CARD9 deficiency; central nervous system; colitis; Candida species; human; CHRONIC MUCOCUTANEOUS CANDIDIASIS; HYPER-IGE SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; CENTRAL-NERVOUS-SYSTEM; FUNGAL-INFECTIONS; CEREBRAL CANDIDIASIS; CEREBROSPINAL-FLUID; IL-17; IMMUNITY; INBORN-ERRORS; MASS LESION;

D O I：

10.1016/j.jaci.2014.12.1930

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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: R7OW 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 Calbicans, 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.

引用

页码：1558 / U269

页数：13

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