New pathogenic and therapeutic paradigms in atopic dermatitis

被引:103
作者
Malajian, Dana [1 ,2 ,3 ]
Guttman-Yassky, Emma [1 ,2 ]
机构
[1] Mt Sinai Sch Med, Icahn Sch Med, Dept Dermatol, New York, NY USA
[2] Mt Sinai Sch Med, Icahn Sch Med, Inst Immunol, New York, NY USA
[3] Columbia Univ, Coll Phys & Surg, New York, NY USA
关键词
Atopic dermatitis; Translational medicine; T-cells; Immune antagonists; ANTIGEN-PRESENTING CELLS; PLACEBO-CONTROLLED TRIAL; INTERLEUKIN-12/23; MONOCLONAL-ANTIBODY; ALLERGY CLIN IMMUNOL; SKIN BARRIER; DOUBLE-BLIND; IFN-GAMMA; STAPHYLOCOCCUS-AUREUS; DENDRITIC CELLS; TH2; CYTOKINES;
D O I
10.1016/j.cyto.2014.11.023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Atopic Dermatitis (AD) is a common inflammatory skin disease with increasing prevalence in industrialized countries. Up to one-third of adults with AD have moderate-to-severe disease, leading to a large, unmet need for effective treatments. While current therapeutics focus mainly on symptom control, major advances have been made in translational research, with the goal of developing drugs to eradicate disease. A translational revolution is now occurring in AD, similar to the one that has occurred in psoriasis over the past decade. Research has focused on elucidating immune pathways responsible for AD, including Th2, Th22, and Th17 pathways, with testing of immune antagonists specific to these axes. An IL-4R antagonist, dupilumab, is the first drug that shows great promise in phase II trials. By studying clinical and molecular responses following treatment with specific immune antagonists, our understanding of and ability to treat AD will expand. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:311 / 318
页数:8
相关论文
共 181 条
[1]   Mechanisms of allergen-specific immunotherapy [J].
Akdis, Cezmi A. ;
Akdis, Muebeccel .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2011, 127 (01) :18-27
[2]   Increased activation-induced cell death of high IFN-γ-producing TH1 cells as a mechanism of TH2 predominance in atopic diseases [J].
Akkoc, Tunc ;
de Koning, Pieter J. A. ;
Ruckert, Beate ;
Barlan, Isil ;
Akdis, Mubeccel ;
Akdis, Cezmi A. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 121 (03) :652-658
[3]   Cutting edge:: CD1a+ antigen-presenting cells in human dermis respond rapidly to CCR7 Ligands [J].
Angel, Catherine E. ;
George, Elizabeth ;
Brooks, Anna E. S. ;
Ostrovsky, Lena L. ;
Brown, Tim La H. ;
Dunbar, P. Rod .
JOURNAL OF IMMUNOLOGY, 2006, 176 (10) :5730-5734
[4]   Tralokinumab for uncontrolled asthma [J].
Antohe, Ileana ;
Croitoru, Rodica ;
Antoniu, Sabina .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2013, 13 (02) :323-326
[5]   The relationship between serum levels of total IgE, IL-18, IL-12, IFN-γ and disease severity in children with atopic dermatitis [J].
Aral, Murat ;
Arican, Ozer ;
Gul, Mustafa ;
Sasmaz, Sezai ;
Kocturk, Sumeyra Alkis ;
Kastal, Ummugulsum ;
Ekerbicer, Hasan Cetin .
MEDIATORS OF INFLAMMATION, 2006, 2006
[6]   A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis [J].
Ash, Zoe ;
Gaujoux-Viala, Cecile ;
Gossec, Laure ;
Hensor, Elizabeth M. A. ;
FitzGerald, Oliver ;
Winthrop, Kevin ;
van der Heijde, Desiree ;
Emery, Paul ;
Smolen, Josef S. ;
Marzo-Ortega, Helena .
ANNALS OF THE RHEUMATIC DISEASES, 2012, 71 (03) :319-326
[7]   Anti-IgE - emerging opportunities for Omalizumab [J].
Babu, K. Suresh ;
Polosa, Riccardo ;
Morjaria, Jaymin B. .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2013, 13 (05) :765-777
[8]   Efficacy of allergen-specific immunotherapy for atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials [J].
Bae, Jung Min ;
Choi, Yoon Young ;
Park, Chang Ook ;
Chung, Kee Yang ;
Lee, Kwang Hoon .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2013, 132 (01) :110-117
[9]   Genomewide association studies in allergy and the influence of ethnicity [J].
Barnes, Kathleen C. .
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 10 (05) :427-433
[10]   Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis [J].
Beck, Lisa A. ;
Thaci, Diamant ;
Hamilton, Jennifer D. ;
Graham, Neil M. ;
Bieber, Thomas ;
Rocklin, Ross ;
Ming, Jeffrey E. ;
Ren, Haobo ;
Kao, Richard ;
Simpson, Eric ;
Ardeleanu, Marius ;
Weinstein, Steven P. ;
Pirozzi, Gianluca ;
Guttman-Yassky, Emma ;
Suarez-Farinas, Mayte ;
Hager, Melissa D. ;
Stahl, Neil ;
Yancopoulos, George D. ;
Radin, Allen R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (02) :130-139