Primary immunodeficiencies underlying fungal infections.
OBJECTIVE
We review the primary immunodeficiencies (PIDs) underlying an increasing variety of superficial and invasive fungal infections. We also stress that the occurrence of such fungal infections should lead physicians to search for the corresponding single-gene inborn errors of immunity. Finally, we suggest that other fungal infections may also result from hitherto unknown inborn errors of immunity, at least in some patients with no known risk factors.


RESULTS
An increasing number of PIDs are being shown to underlie fungal infectious diseases in children and young adults. Inborn errors of the phagocyte NADPH oxidase complex (chronic granulomatous disease), severe congenital neutropenia (SCN) and leukocyte adhesion deficiency type I confer a predisposition to invasive aspergillosis and candidiasis. More rarely, inborn errors of interferon-γ immunity underlie endemic mycoses. Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis.


CONCLUSIONS
CMC, invasive candidiasis, invasive aspergillosis, deep dermatophytosis, pneumocystosis, and endemic mycoses can all be caused by PIDs. Each type of infection is highly suggestive of a specific type of PID. In the absence of overt risk factors, single-gene inborn errors of immunity should be sought in children and young adults with these and other fungal diseases.
aLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980 Necker Medical School, Imagine Institute and Paris Descartes University, Sorbonne Paris Cité bInfectious Diseases and Tropical Medicine Unit, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University cPasteur Institute, National Reference Center of Invasive Mycoses and Antifungals, Paris, France dSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA eStudy Center for Immunodeficiency fPediatric Hematology-Immunology Unit, Necker Enfants-Malades Hospital, AP-HP, and Paris Descartes University, Sorbonne Paris Cité, Paris, France.
Fanny
F
Lanternier
Sophie
S
Cypowyj
Capucine
C
Picard
Jacinta
J
Bustamante
Olivier
O
Lortholary
Jean-Laurent
JL
Casanova
Anne
A
Puel
D000293:Adolescent; D000328:Adult; D001228:Aspergillosis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D020381:Interleukin-17 / Q000276:immunology; D008297:Male; D009181:Mycoses / Q000235:genetics* / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001323:Autoantibodies; D020381:Interleukin-17