title: A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type.
abstract: BACKGROUND
  Atopic dermatitis (AD) can be classified into the major extrinsic type with high serum IgE levels and impaired barrier, and the minor intrinsic type with normal IgE levels and unimpaired barrier.
  
  
  OBJECTIVE
  To characterize the intrinsic type of Japanese AD patients in the T helper cell polarization in relation to the barrier condition.
  
  
  METHODS
  Enrolled in this study were 21 AD patients with IgE<200kU/L (IgE-low group; 82.5±59.6kU/L) having unimpaired barrier, and 48 AD patients with IgE>500kU/L (IgE-high group; 8.050±10.400kU/L). We investigated filaggrin gene (FLG) mutations evaluated in the eight loci common to Japanese patients, circulating Th1, Th2 and Th17 cells by intracellular cytokine staining and flow cytometry, and blood levels of CCL17/TARC, IL-18, and substance P by ELISA.
  
  
  RESULTS
  The incidence of FLG mutations was significantly lower in the IgE-low group (10.5%) than the IgE-high group (44.4%) (normal individuals, 3.7%). The percentage of IFN-γ-producing Th1, but not Th2 or Th17, was significantly higher in the IgE-low than IgE-high group. Accordingly, Th2-attracting chemokine CCL17/TARC, was significantly lower in the IgE-low than the IgE-high group. There were no differences between them in serum IL-18 levels, or the plasma substance P levels or its correlation with pruritus.
  
  
  CONCLUSIONS
  The IgE-low group differed from the IgE-high group in that it had much less FLG mutations, increased frequency of Th1 cells, and lower levels of CCL17. In the intrinsic type, non-protein antigens capable of penetrating the unimpaired barrier may induce a Th1 eczematous response.
authors.affiliation: Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Kabashima-Kubo
authors.forename: Motonobu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sakabe
authors.forename: Kazunari
authors.initials: K
authors.lastname: Sugita
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hino
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mori
authors.forename: Miwa
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Bito
authors.forename: Kenji
authors.initials: K
authors.lastname: Kabashima
authors.forename: Koetsu
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nomura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nomura
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D054414:Chemokine CCL17 / Q000097:blood; D002648:Child; D004252:DNA Mutational Analysis; D003876:Dermatitis, Atopic / Q000097:blood / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000091344:Filaggrin Proteins; D005434:Flow Cytometry; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000097:blood; D007381:Intermediate Filament Proteins / Q000235:genetics; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012684:Sensory Thresholds; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013373:Substance P / Q000097:blood; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation; D014870:Water Loss, Insensible; D055815:Young Adult
chemical_list: D015415:Biomarkers; C106230:CCL17 protein, human; D054414:Chemokine CCL17; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D020382:Interleukin-18; D007381:Intermediate Filament Proteins; D013373:Substance P; D007073:Immunoglobulin E; D007371:Interferon-gamma