title: Th2 and Th9 responses in patients with chronic mucocutaneous candidiasis and hyper-IgE syndrome.
abstract: 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.
  
  
  
  We investigated whether differential Th2 and Th9 responses may explain the clinical differences.
  
  
  
  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 TGFβ and regulatory T cells were measured in cell culture supernatants by ELISA or flow cytometry, respectively.
  
  
  
  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 TGFβ was involved in the IL-4-induced IL-9 production, TGFβ 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.
  
  
  
  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.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: K L
authors.initials: KL
authors.lastname: Becker
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Rösler
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.|Department of Dermatology, Peking University First Hospital, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Lachmandas
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Kamsteeg
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: C W
authors.initials: CW
authors.lastname: Jacobs
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: L A
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Radboud Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.
authors.forename: F L
authors.initials: FL
authors.lastname: van de Veerdonk
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002178:Candidiasis, Chronic Mucocutaneous / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007589:Job Syndrome / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007073:Immunoglobulin E
keywords: 
  Aspergillus fumigatus
  ; 
  Candida albicans
  ; 
  Staphylococcus aureus
  ; Th2 response; chronic mucocutaneous candidiasis; fungal allergy; hyper-IgE syndrome; interleukin-13; interleukin-5; interleukin-9