Milder clinical hyperimmunoglobulin E syndrome phenotype is associated with partial interleukin-17 deficiency

• Published in: Clinical and experimental immunology 2010-01, Vol.159 (1), p.57-64
• Main Authors: van de Veerdonk, F.L, Marijnissen, R, Joosten, L.A.B, Kullberg, B.J, Drenth, J.P.H, Netea, M.G, van der Meer, J.W.M
• Format: Article
• Language: English
• Subjects: Adult; Analytical, structural and metabolic biochemistry; Biological and medical sciences; C. albicans; Candida albicans - immunology; Candidia; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cytokines; Female; Fundamental and applied biological sciences. Psychology; Genotype & phenotype; HIES; Humans; IL-17; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-10 - pharmacology; Interleukin-17 - deficiency; Interleukin-17 - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - pharmacology; Job Syndrome - diagnosis; Job Syndrome - immunology; Job Syndrome - metabolism; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Male; Medical research; Middle Aged; Mutation; Pedigree; S. aureus; Signal Transduction - immunology; Staphylococcus aureus; Staphylococcus aureus - immunology; STAT3; STAT3 Transcription Factor - genetics; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Translational Studies
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.04043.x

Mutations in the signal transducer and activator of transcription 3 (STAT3) were reported to cause hyperimmunoglobulin E syndrome (HIES). The present study investigates T helper type 17 (Th17) responses triggered by the relevant stimuli Staphylococcus aureus and Candidia albicans in five 'classical' HIES patients, and a family with three patients who all had a milder HIES phenotype. We demonstrate that patients with various forms of HIES have different defects in their Th17 response to S. aureus and C. albicans, and this is in line with the clinical features of the disease. Interestingly, a partial deficiency of interleukin (IL)-17 production, even when associated with STAT3 mutations, leads to a milder clinical phenotype. We also observed defective Th17 responses in patients with the 'classical' presentation of the disease but without STAT3 mutations. These data demonstrate that defective IL-17 production in response to specific pathogens can differ between patients with HIES and that the extent of the defective Th17 response determines their clinical phenotype.