title: Quantitative defects in invariant NKT cells and TLR responses in patients with hyper-IgE syndrome.
abstract: BACKGROUND
  Autosomal dominant hyper-IgE syndrome (AD-HIES) is a primary immunodeficiency mainly caused by mutations in STAT3, a signalling molecule implicated in the development of appropriate immune responses. We aimed to characterise the innate immune response in AD-HIES.
  
  
  METHODS
  The frequency of innate immune cells in peripheral blood (PB) from seven AD-HIES patients and healthy controls were determined. CD80/CD86 surface expression and cytokine levels in supernatants from PBMC after stimulation with TLR-2, -4 and -9 agonists were also measured by flow cytometry. In addition, several SNPs within these TLR genes in genomic DNA samples from patients and controls were examined.
  
  
  RESULTS
  A significantly reduced number of PB iNKT cells was observed in the AD-HIES group. CpG-stimulated pDC and mDC from patients exhibited a lower increase in the expression of the costimulatory molecule CD80. We also observed an increase in the secretion of IL-12p70, TNF-alpha and IL-10 in PBMC from HIES patients after LTA or LPS stimuli. No association was found between the different SNPs detected and the HIES phenotype.
  
  
  CONCLUSIONS
  These findings demonstrate that important mediators of the innate immunity responses are affected in AD-HIES. More studies are necessary to investigate how the STAT3 function interferes with development of iNKT cells and TLR-mediated responses.
authors: Grupo de Inmunodeficiencias Primarias, Colombia.
authors: S
authors: S
authors: Gutierrez-Hincapié
authors: Programa de Estudio y Control de Enfermedades Tropicales - PECET, Colombia.
authors: C E
authors: CE
authors: Muskus-López
authors: Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
authors: C J
authors: CJ
authors: Montoya
authors: Grupo de Inmunodeficiencias Primarias, Colombia. Electronic address: cmtruji@gmail.com.
authors: C M
authors: CM
authors: Trujillo-Vargas
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004252:DNA Mutational Analysis; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D050796:STAT3 Transcription Factor / Q000235:genetics; D013682:Teichoic Acids / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000819:agonists* / Q000235:genetics; D055815:Young Adult
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D050796:STAT3 Transcription Factor; D013682:Teichoic Acids; D051193:Toll-Like Receptors; C009900:lipoteichoic acid
keywords: Autosomal dominant hyper-IgE syndrome; Cytokines; Innate immunity; Toll-like receptor; iNKT cells