Th2 and Th9 responses in patients with chronic mucocutaneous candidiasis and hyper-IgE syndrome.
Clin Exp Allergy
; 46(12): 1564-1574, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27474157
ABSTRACT
BACKGROUND:
STAT1 mutations cause chronic mucocutaneous candidiasis (CMC), while STAT3 mutations cause hyper-IgE syndrome (HIES). CMC and HIES patients have T helper (Th) 17 defects suffering from mucosal Candida infections, but only patients with HIES show an allergic phenotype with eczema, eosinophilia and high IgE levels.OBJECTIVE:
We investigated whether differential Th2 and Th9 responses may explain the clinical differences.METHODS:
Peripheral blood mononuclear cells of patients with CMC (n = 4), patients with HIES (n = 4), patients with atopic dermatitis (n = 4) and healthy volunteers (n = 13) were stimulated with Candida and Staphylococcus aureus, with and without IL-4. The cytokines IL-5, IL-13, IL-9, IL-17 and TGFß and regulatory T cells were measured in cell culture supernatants by ELISA or flow cytometry, respectively.RESULTS:
Peripheral blood mononuclear cells of patients with CMC showed a significantly impaired production of the Th2 cytokines IL-5 and IL-13, especially in the presence of IL-4. Moreover, IL-9 production was significantly lower in patients with CMC compared to healthy controls. In contrast, patients with HIES and patients with AD showed normal IL-5 and IL-13 production, while IL-9 production was significantly lower in patients with HIES compared to healthy controls. Although TGFß was involved in the IL-4-induced IL-9 production, TGFß levels and the frequency of regulatory T cells did not differ between patients with HIES and controls. Flow cytometry analysis demonstrated an IL-9+ IL-17+ CD4+ subset in healthy controls after stimulation with Candida which was less present in patients with HIES.CONCLUSION:
Patients with CMC have a general Th defect including Th2 and Th9, while patients with HIES have normal Th2 cytokines. These differences are in line with their clinical presentation. Surprisingly, the allergic cytokine IL-9 was deficient in both HIES and CMC, suggesting a Th-17-derived origin.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Candidíase Mucocutânea Crônica
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Linfócitos T Auxiliares-Indutores
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Síndrome de Job
Tipo de estudo:
Observational_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Exp Allergy
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Holanda