title: Atopic dermatitis, STAT3- and DOCK8-hyper-IgE syndromes differ in IgE-based sensitization pattern.
abstract: BACKGROUND
  Increased serum IgE levels are characteristic but not specific for allergic diseases. Particularly, severe atopic dermatitis (AD) overlaps with hyper-IgE syndromes (HIES) regarding eczema, eosinophilia, and increased serum IgE levels. HIES are primary immunodeficiencies due to monogenetic defects such as in the genes DOCK8 and STAT3. As it is not known to date why allergic manifestations are not present in all HIES entities, we assessed the specificity of serum IgE of AD and HIES patients in the context of clinical and immunological findings.
  
  
  METHODS
  Clinical data, skin prick tests, specific IgE to aero- and food allergens, and T helper (Th) subpopulations were compared in AD and molecularly defined HIES patients.
  
  
  RESULTS
  Total serum IgE levels were similarly increased in STAT3-HIES, DOCK8-HIES, and AD patients. The ratio of aeroallergen-specific IgE to total IgE was highest in AD, whereas DOCK8-HIES patients showed the highest specific serum IgE against food allergens. Overall, clinical allergy and skin prick test results complied with the specific IgE results. Th2-cell numbers were significantly increased in DOCK8-HIES and AD patients compared to STAT3-HIES patients and controls. AD patients showed significantly higher nTreg-cell counts compared to STAT3-HIES and control individuals. High Th17-cell counts were associated with asthma. Specific IgE values, skin prick test, and T-cell subsets of STAT3-HIES patients were comparable with those of healthy individuals except decreased Th17-cell counts.
  
  
  CONCLUSIONS
  Hyper-IgE syndromes and atopic dermatitis patients showed different sensitization pattern of serum IgE corresponding to the allergic disease manifestations and Th-cell subset data, suggesting a key role of DOCK8 in the development of food allergy.
authors.affiliation: University Children's Hospital at Dr. von Haunersches Kinderspital, Ludwig Maximilian University, Munich, Germany; Dermatology and Allergy, Ludwig Maximilian University, Munich, Germany.
authors.forename: A C
authors.initials: AC
authors.lastname: Boos
authors.forename: B
authors.initials: B
authors.lastname: Hagl
authors.forename: A
authors.initials: A
authors.lastname: Schlesinger
authors.forename: B E
authors.initials: BE
authors.lastname: Halm
authors.forename: N
authors.initials: N
authors.lastname: Ballenberger
authors.forename: M
authors.initials: M
authors.lastname: Pinarci
authors.forename: V
authors.initials: V
authors.lastname: Heinz
authors.forename: D
authors.initials: D
authors.lastname: Kreilinger
authors.forename: B D
authors.initials: BD
authors.lastname: Spielberger
authors.forename: L F
authors.initials: LF
authors.lastname: Schimke-Marques
authors.forename: J
authors.initials: J
authors.lastname: Sawalle-Belohradsky
authors.forename: B H
authors.initials: BH
authors.lastname: Belohradsky
authors.forename: B
authors.initials: B
authors.lastname: Przybilla
authors.forename: B
authors.initials: B
authors.lastname: Schaub
authors.forename: A
authors.initials: A
authors.lastname: Wollenberg
authors.forename: E D
authors.initials: ED
authors.lastname: Renner
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D003876:Dermatitis, Atopic / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007589:Job Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology*; D012882:Skin Tests; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D055815:Young Adult
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007073:Immunoglobulin E
keywords: DOCK8 deficiency; IgE-based sensitization pattern; STAT3-hyper-IgE syndrome; atopic dermatitis; hyper-IgE syndromes