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Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis.
J Allergy Clin Immunol 2013; 132(2):361-70JA

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 TH2) was detected in patients with intrinsic AD, particularly TH17 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 TH22 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.

Authors+Show Affiliations

Laboratory for Investigative Dermatology, Rockefeller University, New York, NY, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23777851

Citation

Suárez-Fariñas, Mayte, et al. "Intrinsic Atopic Dermatitis Shows Similar TH2 and Higher TH17 Immune Activation Compared With Extrinsic Atopic Dermatitis." The Journal of Allergy and Clinical Immunology, vol. 132, no. 2, 2013, pp. 361-70.
Suárez-Fariñas M, Dhingra N, Gittler J, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132(2):361-70.
Suárez-Fariñas, M., Dhingra, N., Gittler, J., Shemer, A., Cardinale, I., de Guzman Strong, C., ... Guttman-Yassky, E. (2013). Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. The Journal of Allergy and Clinical Immunology, 132(2), pp. 361-70. doi:10.1016/j.jaci.2013.04.046.
Suárez-Fariñas M, et al. Intrinsic Atopic Dermatitis Shows Similar TH2 and Higher TH17 Immune Activation Compared With Extrinsic Atopic Dermatitis. J Allergy Clin Immunol. 2013;132(2):361-70. PubMed PMID: 23777851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. 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, Y1 - 2013/06/15/ PY - 2013/02/17/received PY - 2013/04/10/revised PY - 2013/04/11/accepted PY - 2013/6/20/entrez PY - 2013/6/20/pubmed PY - 2013/10/19/medline KW - AD KW - Atopic dermatitis KW - DC KW - Dendritic cell KW - FLG KW - FOXP3 KW - Filaggrin KW - Forkhead box protein 3 KW - IHC KW - IgE KW - Immunohistochemistry KW - OX40 ligand KW - OX40L KW - RT-PCR KW - Real-time PCR KW - S100 proteins KW - TNF ligand superfamily 10 KW - TRAIL KW - T cell KW - eczema KW - extrinsic KW - human skin KW - intrinsic KW - keratinocytes SP - 361 EP - 70 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 132 IS - 2 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 TH2) was detected in patients with intrinsic AD, particularly TH17 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 TH22 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/23777851/Intrinsic_atopic_dermatitis_shows_similar_TH2_and_higher_TH17_immune_activation_compared_with_extrinsic_atopic_dermatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(13)00693-3 DB - PRIME DP - Unbound Medicine ER -