Intrinsic atopic dermatitis shows similar TH2 and higher T H17 immune activation compared with extrinsic atopic dermatitis

Mayte Suárez-Fariñas, Nikhil Dhingra, Julia Gittler, Avner Shemer, Irma Cardinale, Cristina De Guzman Strong, James G. Krueger, Emma Guttman-Yassky

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Background: Atopic dermatitis (AD) is classified as extrinsic and intrinsic, representing approximately 80% and 20% of patients with the disease, respectively. Although sharing a similar clinical phenotype, only extrinsic AD is characterized by high serum IgE levels. Because most patients with AD exhibit high IgE levels, an "allergic"/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly TH2/TH22 polarization, and epidermal barrier defects. Objective: We sought to define whether both variants share a common pathogenesis. Methods: We stratified 51 patients with severe AD into extrinsic AD (n = 42) and intrinsic AD (n = 9) groups (with similar mean disease activity/SCORAD scores) and analyzed the molecular and cellular skin pathology of lesional and nonlesional intrinsic AD and extrinsic AD by using gene expression (real-time PCR) and immunohistochemistry. Results: A significant correlation between IgE levels and SCORAD scores (r = 0.76, P < 10 -5) was found only in patients with extrinsic AD. Marked infiltrates of T cells and dendritic cells and corresponding epidermal alterations (keratin 16, Mki67, and S100A7/A8/A9) defined lesional skin of patients with both variants. However, higher activation of all inflammatory axes (including T H2) was detected in patients with intrinsic AD, particularly T H17 and TH22 cytokines. Positive correlations between TH17-related molecules and SCORAD scores were only found in patients with intrinsic AD, whereas only patients with extrinsic AD showed positive correlations between SCORAD scores and TH2 cytokine (IL-4 and IL-5) levels and negative correlations with differentiation products (loricrin and periplakin). Conclusions: Although differences in TH17 and T H22 activation exist between patients with intrinsic AD and those with extrinsic AD, we identified common disease-defining features of T-cell activation, production of polarized cytokines, and keratinocyte responses to immune products. Our data indicate that a TH2 bias is not the sole cause of high IgE levels in patients with extrinsic AD, with important implications for similar therapeutic interventions.

Original languageEnglish (US)
Pages (from-to)361-370
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume132
Issue number2
DOIs
StatePublished - Aug 1 2013

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Atopic Dermatitis
Immunoglobulin E
Cytokines
T-Lymphocytes
Keratin-16
Skin
Langerhans Cells
Interleukin-5
Keratinocytes
Interleukin-4
Real-Time Polymerase Chain Reaction

Keywords

  • Atopic dermatitis
  • eczema
  • extrinsic
  • human skin
  • IgE
  • intrinsic
  • keratinocytes
  • S100 proteins
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Intrinsic atopic dermatitis shows similar TH2 and higher T H17 immune activation compared with extrinsic atopic dermatitis. / Suárez-Fariñas, Mayte; Dhingra, Nikhil; Gittler, Julia; Shemer, Avner; Cardinale, Irma; De Guzman Strong, Cristina; Krueger, James G.; Guttman-Yassky, Emma.

In: Journal of Allergy and Clinical Immunology, Vol. 132, No. 2, 01.08.2013, p. 361-370.

Research output: Contribution to journalArticle

Suárez-Fariñas, M, Dhingra, N, Gittler, J, Shemer, A, Cardinale, I, De Guzman Strong, C, Krueger, JG & Guttman-Yassky, E 2013, 'Intrinsic atopic dermatitis shows similar TH2 and higher T H17 immune activation compared with extrinsic atopic dermatitis', Journal of Allergy and Clinical Immunology, vol. 132, no. 2, pp. 361-370. https://doi.org/10.1016/j.jaci.2013.04.046
Suárez-Fariñas, Mayte ; Dhingra, Nikhil ; Gittler, Julia ; Shemer, Avner ; Cardinale, Irma ; De Guzman Strong, Cristina ; Krueger, James G. ; Guttman-Yassky, Emma. / Intrinsic atopic dermatitis shows similar TH2 and higher T H17 immune activation compared with extrinsic atopic dermatitis. In: Journal of Allergy and Clinical Immunology. 2013 ; Vol. 132, No. 2. pp. 361-370.
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AU - Suárez-Fariñas, Mayte

AU - Dhingra, Nikhil

AU - Gittler, Julia

AU - Shemer, Avner

AU - Cardinale, Irma

AU - De Guzman Strong, Cristina

AU - Krueger, James G.

AU - Guttman-Yassky, Emma

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N2 - Background: Atopic dermatitis (AD) is classified as extrinsic and intrinsic, representing approximately 80% and 20% of patients with the disease, respectively. Although sharing a similar clinical phenotype, only extrinsic AD is characterized by high serum IgE levels. Because most patients with AD exhibit high IgE levels, an "allergic"/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly TH2/TH22 polarization, and epidermal barrier defects. Objective: We sought to define whether both variants share a common pathogenesis. Methods: We stratified 51 patients with severe AD into extrinsic AD (n = 42) and intrinsic AD (n = 9) groups (with similar mean disease activity/SCORAD scores) and analyzed the molecular and cellular skin pathology of lesional and nonlesional intrinsic AD and extrinsic AD by using gene expression (real-time PCR) and immunohistochemistry. Results: A significant correlation between IgE levels and SCORAD scores (r = 0.76, P < 10 -5) was found only in patients with extrinsic AD. Marked infiltrates of T cells and dendritic cells and corresponding epidermal alterations (keratin 16, Mki67, and S100A7/A8/A9) defined lesional skin of patients with both variants. However, higher activation of all inflammatory axes (including T H2) was detected in patients with intrinsic AD, particularly T H17 and TH22 cytokines. Positive correlations between TH17-related molecules and SCORAD scores were only found in patients with intrinsic AD, whereas only patients with extrinsic AD showed positive correlations between SCORAD scores and TH2 cytokine (IL-4 and IL-5) levels and negative correlations with differentiation products (loricrin and periplakin). Conclusions: Although differences in TH17 and T H22 activation exist between patients with intrinsic AD and those with extrinsic AD, we identified common disease-defining features of T-cell activation, production of polarized cytokines, and keratinocyte responses to immune products. Our data indicate that a TH2 bias is not the sole cause of high IgE levels in patients with extrinsic AD, with important implications for similar therapeutic interventions.

AB - Background: Atopic dermatitis (AD) is classified as extrinsic and intrinsic, representing approximately 80% and 20% of patients with the disease, respectively. Although sharing a similar clinical phenotype, only extrinsic AD is characterized by high serum IgE levels. Because most patients with AD exhibit high IgE levels, an "allergic"/IgE-mediated disease pathogenesis was hypothesized. However, current models associate AD with T-cell activation, particularly TH2/TH22 polarization, and epidermal barrier defects. Objective: We sought to define whether both variants share a common pathogenesis. Methods: We stratified 51 patients with severe AD into extrinsic AD (n = 42) and intrinsic AD (n = 9) groups (with similar mean disease activity/SCORAD scores) and analyzed the molecular and cellular skin pathology of lesional and nonlesional intrinsic AD and extrinsic AD by using gene expression (real-time PCR) and immunohistochemistry. Results: A significant correlation between IgE levels and SCORAD scores (r = 0.76, P < 10 -5) was found only in patients with extrinsic AD. Marked infiltrates of T cells and dendritic cells and corresponding epidermal alterations (keratin 16, Mki67, and S100A7/A8/A9) defined lesional skin of patients with both variants. However, higher activation of all inflammatory axes (including T H2) was detected in patients with intrinsic AD, particularly T H17 and TH22 cytokines. Positive correlations between TH17-related molecules and SCORAD scores were only found in patients with intrinsic AD, whereas only patients with extrinsic AD showed positive correlations between SCORAD scores and TH2 cytokine (IL-4 and IL-5) levels and negative correlations with differentiation products (loricrin and periplakin). Conclusions: Although differences in TH17 and T H22 activation exist between patients with intrinsic AD and those with extrinsic AD, we identified common disease-defining features of T-cell activation, production of polarized cytokines, and keratinocyte responses to immune products. Our data indicate that a TH2 bias is not the sole cause of high IgE levels in patients with extrinsic AD, with important implications for similar therapeutic interventions.

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