Advances and highlights in mechanisms of allergic disease in 2015
2016; Elsevier BV; Volume: 137; Issue: 6 Linguagem: Inglês
10.1016/j.jaci.2016.02.010
ISSN1097-6825
AutoresPaulina Wawrzyniak, Cezmi A. Akdiş, Fred D. Finkelman, Marc E. Rothenberg,
Tópico(s)Dermatology and Skin Diseases
ResumoThis review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. This review highlights some of the advances in mechanisms of allergic disease, particularly anaphylaxis, including food allergy, drug hypersensitivity, atopic dermatitis (AD), allergic conjunctivitis, and airway diseases. During the last year, a mechanistic advance in food allergy was achieved by focusing on mechanisms of allergen sensitization. Novel biomarkers and treatment for mastocytosis were presented in several studies. Novel therapeutic approaches in the treatment of atopic dermatitis and psoriasis showed that promising supplementation of the infant's diet in the first year of life with immunoactive prebiotics might have a preventive role against early development of AD and that therapeutic approaches to treat AD in children might be best directed to the correction of a TH2/TH1 imbalance. Several studies were published emphasizing the role of the epithelial barrier in patients with allergic diseases. An impaired skin barrier as a cause for sensitization to food allergens in children and its relationship to filaggrin mutations has been an important development. Numerous studies presented new approaches for improvement of epithelial barrier function and novel biologicals used in the treatment of inflammatory skin and eosinophilic diseases. In addition, novel transcription factors and signaling molecules that can develop as new possible therapeutic targets have been reported. This review highlights key advances in mechanisms of anaphylaxis, systemic mastocytosis, drug hypersensitivity, and epithelial barrier dysfunction in patients with atopic dermatitis (AD) and asthma, particularly those reported in 2015. Some of the key advances are summarized in Table I.1Altman A.M. Camargo Jr., C.A. Simons F.E. Lieberman P. Sampson H.A. Schwartz L.B. et al.Anaphylaxis in America: a national physician survey.J Allergy Clin Immunol. 2015; 135: 830-833Abstract Full Text Full Text PDF PubMed Google Scholar, 2Turner P.J. Gowland M.H. Sharma V. Ierodiakonou D. Harper N. Garcez T. et al.Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012.J Allergy Clin Immunol. 2015; 135: 956-963.e1Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 3Mullins R.J. Dear K.B. Tang M.L. Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012.J Allergy Clin Immunol. 2015; 136: 367-375Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar, 4Nocerino R. Leone L. Cosenza L. Berni Canani R. Increasing rate of hospitalizations for food-induced anaphylaxis in Italian children: an analysis of the Italian Ministry of Health database.J Allergy Clin Immunol. 2015; 135: 833-835.e3Abstract Full Text Full Text PDF PubMed Google Scholar, 5Martino D. Dang T. Sexton-Oates A. Prescott S. Tang M.L. Dharmage S. et al.Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.J Allergy Clin Immunol. 2015; 135 (e1-12): 1319-1328Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar, 6Zanotti R. Lombardo C. Passalacqua G. Caimmi C. Bonifacio M. De Matteis G. et al.Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels.J Allergy Clin Immunol. 2015; 136: 135-139Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 7Nassiri M. Eckermann O. Babina M. Edenharter G. Worm M. Serum levels of 9alpha,11beta-PGF and cysteinyl leukotrienes are useful biomarkers of anaphylaxis.J Allergy Clin Immunol. 2016; 137: 312-314.e7Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 8Weng Z. Patel A.B. Panagiotidou S. Theoharides T.C. The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells.J Allergy Clin Immunol. 2015; 135: 1044-1052.e5Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 9Broesby-Olsen S. Oropeza A.R. Bindslev-Jensen C. Vestergaard H. Moller M.B. Siebenhaar F. et al.Recognizing mastocytosis in patients with anaphylaxis: value of KIT D816V mutation analysis of peripheral blood.J Allergy Clin Immunol. 2015; 135: 262-264Abstract Full Text Full Text PDF PubMed Google Scholar, 10Vos B.J. van der Veer E. van Voorst Vader P.C. Mulder A.B. van der Heide S. Arends S. et al.Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects.J Allergy Clin Immunol. 2015; 135: 792-798Abstract Full Text Full Text PDF PubMed Google Scholar, 11Yip K.H. Kolesnikoff N. Yu C. Hauschild N. Taing H. Biggs L. et al.Mechanisms of vitamin D(3) metabolite repression of IgE-dependent mast cell activation.J Allergy Clin Immunol. 2014; 133 (e1-14): 1356-1364Abstract Full Text Full Text PDF PubMed Google Scholar, 12Noda S. Krueger J.G. Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases.J Allergy Clin Immunol. 2015; 135: 324-336Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 13Czarnowicki T. Esaki H. Gonzalez J. Malajian D. Shemer A. Noda S. et al.Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.J Allergy Clin Immunol. 2015; 136: 941-951.e3Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 14Suarez-Farinas M. Ungar B. Noda S. Shroff A. Mansouri Y. Fuentes-Duculan J. et al.Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing.J Allergy Clin Immunol. 2015; 136: 1277-1287Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar, 15Brough H.A. Liu A.H. Sicherer S. Makinson K. Douiri A. Brown S.J. et al.Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy.J Allergy Clin Immunol. 2015; 135: 164-170Abstract Full Text Full Text PDF PubMed Google Scholar, 16Pellerin L. Paul C. Schmitt A.M. Serre G. Simon M. Bleomycin hydrolase downregulation in lesional skin of adult atopic dermatitis patients is independent of FLG gene mutations.J Allergy Clin Immunol. 2014; 134: 1459-1461.e7Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 17Kim J.H. Bae H.C. Ko N.Y. Lee S.H. Jeong S.H. Lee H. et al.Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) phosphorylation in keratinocytes.J Allergy Clin Immunol. 2015; 136: 205-208.e9Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar, 18Amano W. Nakajima S. Kunugi H. Numata Y. Kitoh A. Egawa G. et al.The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling.J Allergy Clin Immunol. 2015; 136: 667-677.e7Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 19Czarnowicki T. Malajian D. Khattri S. da Rosa J.C. Dutt R. Finney R. et al.Petrolatum: Barrier repair and antimicrobial responses underlying this "inert" moisturizer.J Allergy Clin Immunol. 2016; 137: 1091-1102.e7Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 20Krueger J.G. Ferris L.K. Menter A. Wagner F. White A. Visvanathan S. et al.Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2015; 136: 116-124.e7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar, 21Lin C.H. Chen J.K. Ko T.M. Wei C.Y. Wu J.Y. Chung W.H. et al.Immunologic basis for allopurinol-induced severe cutaneous adverse reactions: HLA-B*58:01-restricted activation of drug-specific T cells and molecular interaction.J Allergy Clin Immunol. 2015; 135: 1063-1065.e5Abstract Full Text Full Text PDF PubMed Google Scholar, 22Li H. Li C. Zhang H. Zhang L. Cheng R. Li M. et al.Effects of lidocaine on regulatory T cells in atopic dermatitis.J Allergy Clin Immunol. 2016; 137: 613-617.e5Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 23MacDonald K.G. Dawson N.A. Huang Q. Dunne J.V. Levings M.K. Broady R. Regulatory T cells produce profibrotic cytokines in the skin of patients with systemic sclerosis.J Allergy Clin Immunol. 2015; 135: 946.e9Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar, 24Akhabir L. Berube J.C. Bosse Y. Laviolette M. Hao K. Nickle D.C. et al.Lung expression quantitative trait loci data set identifies important functional polymorphisms in the asthma-associated IL1RL1 region.J Allergy Clin Immunol. 2014; 134: 729-731Abstract Full Text Full Text PDF PubMed Google Scholar, 25Ubel C. Sopel N. Graser A. Hildner K. Reinhardt C. Zimmermann T. et al.The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell-driven immune responses in the setting of allergic asthma.J Allergy Clin Immunol. 2014; 133 (e1-9): 198-206Abstract Full Text Full Text PDF PubMed Google Scholar, 26Madritsch C. Eckl-Dorna J. Blatt K. Ellinger I. Kundi M. Niederberger V. et al.Antibody conjugates bispecific for intercellular adhesion molecule 1 and allergen prevent migration of allergens through respiratory epithelial cell layers.J Allergy Clin Immunol. 2015; 136: 490-493.e11Abstract Full Text Full Text PDF PubMed Google Scholar, 27Kubo T. Wawrzyniak P. Morita H. Sugita K. Wanke K. Kast J.I. et al.CpG-DNA enhances the tight junction integrity of the bronchial epithelial cell barrier.J Allergy Clin Immunol. 2015; 136 (e1-8): 1413-1416Abstract Full Text Full Text PDF PubMed Google Scholar, 28Li J.J. Tay H.L. Maltby S. Xiang Y. Eyers F. Hatchwell L. et al.MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by reducing protein phosphatase 2A activity.J Allergy Clin Immunol. 2015; 136: 462-473Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 29Wen T. Stucke E.M. Grotjan T.M. Kemme K.A. Abonia J.P. Putnam P.E. et al.Molecular diagnosis of eosinophilic esophagitis by gene expression profiling.Gastroenterology. 2013; 145: 1289-1299Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar, 30Rothenberg M.E. Wen T. Greenberg A. Alpan O. Enav B. Hirano I. et al.Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis.J Allergy Clin Immunol. 2015; 135: 500-507Abstract Full Text Full Text PDF PubMed Google Scholar, 31Ilmarinen P. Moilanen E. Erjefalt J.S. Kankaanranta H. The polyamine spermine promotes survival and activation of human eosinophils.J Allergy Clin Immunol. 2015; 136: 482-484.e11Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 32Jutel M. Agache I. Bonini S. Burks A.W. Calderon M. Canonica W. et al.International consensus on allergy immunotherapy.J Allergy Clin Immunol. 2015; 136: 556-568Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar, 33Akdis M. Akdis C.A. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens.J Allergy Clin Immunol. 2014; 133: 621-631Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar, 34Tsai Y.G. Lai J.C. Yang K.D. Hung C.H. Yeh Y.J. Lin C.Y. Enhanced CD46-induced regulatory T cells suppress allergic inflammation after Dermatophagoides pteronyssinus-specific immunotherapy.J Allergy Clin Immunol. 2014; 134: 1206-1209.e1Abstract Full Text Full Text PDF PubMed Google Scholar, 35Stanic B. van de Veen W. Wirz O.F. Ruckert B. Morita H. Sollner S. et al.IL-10-overexpressing B cells regulate innate and adaptive immune responses.J Allergy Clin Immunol. 2015; 135: 771-780.e8Abstract Full Text Full Text PDF PubMed Google Scholar, 36Ferstl R. Frei R. Schiavi E. Konieczna P. Barcik W. Ziegler M. et al.Histamine receptor 2 is a key influence in immune responses to intestinal histamine-secreting microbes.J Allergy Clin Immunol. 2014; 134: 744-746.e3Abstract Full Text Full Text PDF PubMed Google Scholar, 37Shamji M.H. Layhadi J.A. Scadding G.W. Cheung D.K. Calderon M.A. Turka L.A. et al.Basophil expression of diamine oxidase: a novel biomarker of allergen immunotherapy response.J Allergy Clin Immunol. 2015; 135: 913-921.e9Abstract Full Text Full Text PDF PubMed Scopus (17) Google ScholarTable IKey advancesAdvanceReferencesAnaphylaxis Increased prevalence of anaphylaxisAltman et al,1Altman A.M. Camargo Jr., C.A. Simons F.E. Lieberman P. Sampson H.A. Schwartz L.B. et al.Anaphylaxis in America: a national physician survey.J Allergy Clin Immunol. 2015; 135: 830-833Abstract Full Text Full Text PDF PubMed Google Scholar Turner et al,2Turner P.J. Gowland M.H. Sharma V. Ierodiakonou D. Harper N. Garcez T. et al.Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012.J Allergy Clin Immunol. 2015; 135: 956-963.e1Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Mullins et al,3Mullins R.J. Dear K.B. Tang M.L. Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012.J Allergy Clin Immunol. 2015; 136: 367-375Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Nocerino et al,4Nocerino R. Leone L. Cosenza L. Berni Canani R. Increasing rate of hospitalizations for food-induced anaphylaxis in Italian children: an analysis of the Italian Ministry of Health database.J Allergy Clin Immunol. 2015; 135: 833-835.e3Abstract Full Text Full Text PDF PubMed Google Scholar Martino et al,5Martino D. Dang T. Sexton-Oates A. Prescott S. Tang M.L. Dharmage S. et al.Blood DNA methylation biomarkers predict clinical reactivity in food-sensitized infants.J Allergy Clin Immunol. 2015; 135 (e1-12): 1319-1328Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar Sicherer et al38Sicherer S.H. Leung D.Y. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.J Allergy Clin Immunol. 2015; 135: 357-367Abstract Full Text Full Text PDF PubMed Google Scholar Novel biomarkers and treatment for patients with mastocytosisZanotti et al,6Zanotti R. Lombardo C. Passalacqua G. Caimmi C. Bonifacio M. De Matteis G. et al.Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels.J Allergy Clin Immunol. 2015; 136: 135-139Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Nassiri et al,7Nassiri M. Eckermann O. Babina M. Edenharter G. Worm M. Serum levels of 9alpha,11beta-PGF and cysteinyl leukotrienes are useful biomarkers of anaphylaxis.J Allergy Clin Immunol. 2016; 137: 312-314.e7Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Weng et al,8Weng Z. Patel A.B. Panagiotidou S. Theoharides T.C. The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells.J Allergy Clin Immunol. 2015; 135: 1044-1052.e5Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar Broesby-Olsen et al,9Broesby-Olsen S. Oropeza A.R. Bindslev-Jensen C. Vestergaard H. Moller M.B. Siebenhaar F. et al.Recognizing mastocytosis in patients with anaphylaxis: value of KIT D816V mutation analysis of peripheral blood.J Allergy Clin Immunol. 2015; 135: 262-264Abstract Full Text Full Text PDF PubMed Google Scholar Vos et al,10Vos B.J. van der Veer E. van Voorst Vader P.C. Mulder A.B. van der Heide S. Arends S. et al.Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects.J Allergy Clin Immunol. 2015; 135: 792-798Abstract Full Text Full Text PDF PubMed Google Scholar Yip et al11Yip K.H. Kolesnikoff N. Yu C. Hauschild N. Taing H. Biggs L. et al.Mechanisms of vitamin D(3) metabolite repression of IgE-dependent mast cell activation.J Allergy Clin Immunol. 2014; 133 (e1-14): 1356-1364Abstract Full Text Full Text PDF PubMed Google ScholarAD Therapeutic approaches in patients with AD and psoriasisNoda et al,12Noda S. Krueger J.G. Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases.J Allergy Clin Immunol. 2015; 135: 324-336Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Czarnowicki et al,13Czarnowicki T. Esaki H. Gonzalez J. Malajian D. Shemer A. Noda S. et al.Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)(+) TH2/TH1 cell imbalance, whereas adults acquire CLA(+) TH22/TC22 cell subsets.J Allergy Clin Immunol. 2015; 136: 941-951.e3Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Suarez-Farinas et al14Suarez-Farinas M. Ungar B. Noda S. Shroff A. Mansouri Y. Fuentes-Duculan J. et al.Alopecia areata profiling shows TH1, TH2, and IL-23 cytokine activation without parallel TH17/TH22 skewing.J Allergy Clin Immunol. 2015; 136: 1277-1287Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Impaired skin barrier causes sensitization to food allergens in childrenBrough et al15Brough H.A. Liu A.H. Sicherer S. Makinson K. Douiri A. Brown S.J. et al.Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy.J Allergy Clin Immunol. 2015; 135: 164-170Abstract Full Text Full Text PDF PubMed Google Scholar Novel biologicals used in treatment of inflammatory skin diseasesKrueger et al,20Krueger J.G. Ferris L.K. Menter A. Wagner F. White A. Visvanathan S. et al.Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial.J Allergy Clin Immunol. 2015; 136: 116-124.e7Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Lin et al,21Lin C.H. Chen J.K. Ko T.M. Wei C.Y. Wu J.Y. Chung W.H. et al.Immunologic basis for allopurinol-induced severe cutaneous adverse reactions: HLA-B*58:01-restricted activation of drug-specific T cells and molecular interaction.J Allergy Clin Immunol. 2015; 135: 1063-1065.e5Abstract Full Text Full Text PDF PubMed Google Scholar Li et al,22Li H. Li C. Zhang H. Zhang L. Cheng R. Li M. et al.Effects of lidocaine on regulatory T cells in atopic dermatitis.J Allergy Clin Immunol. 2016; 137: 613-617.e5Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar MacDonald et al23MacDonald K.G. Dawson N.A. Huang Q. Dunne J.V. Levings M.K. Broady R. Regulatory T cells produce profibrotic cytokines in the skin of patients with systemic sclerosis.J Allergy Clin Immunol. 2015; 135: 946.e9Abstract Full Text Full Text PDF PubMed Scopus (13) Google ScholarAsthma Bronchial epithelial barrier functionPellerin et al,16Pellerin L. Paul C. Schmitt A.M. Serre G. Simon M. Bleomycin hydrolase downregulation in lesional skin of adult atopic dermatitis patients is independent of FLG gene mutations.J Allergy Clin Immunol. 2014; 134: 1459-1461.e7Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Kim et al,17Kim J.H. Bae H.C. Ko N.Y. Lee S.H. Jeong S.H. Lee H. et al.Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) phosphorylation in keratinocytes.J Allergy Clin Immunol. 2015; 136: 205-208.e9Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Amano et al,18Amano W. Nakajima S. Kunugi H. Numata Y. Kitoh A. Egawa G. et al.The Janus kinase inhibitor JTE-052 improves skin barrier function through suppressing signal transducer and activator of transcription 3 signaling.J Allergy Clin Immunol. 2015; 136: 667-677.e7Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Czarnowicki et al,19Czarnowicki T. Malajian D. Khattri S. da Rosa J.C. Dutt R. Finney R. et al.Petrolatum: Barrier repair and antimicrobial responses underlying this "inert" moisturizer.J Allergy Clin Immunol. 2016; 137: 1091-1102.e7Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar Madritsch et al,26Madritsch C. Eckl-Dorna J. Blatt K. Ellinger I. Kundi M. Niederberger V. et al.Antibody conjugates bispecific for intercellular adhesion molecule 1 and allergen prevent migration of allergens through respiratory epithelial cell layers.J Allergy Clin Immunol. 2015; 136: 490-493.e11Abstract Full Text Full Text PDF PubMed Google Scholar Kubo et al27Kubo T. Wawrzyniak P. Morita H. Sugita K. Wanke K. Kast J.I. et al.CpG-DNA enhances the tight junction integrity of the bronchial epithelial cell barrier.J Allergy Clin Immunol. 2015; 136 (e1-8): 1413-1416Abstract Full Text Full Text PDF PubMed Google Scholar IL1RL1 gene has been implicated in the pathogenesis of asthmaAkhabir et al24Akhabir L. Berube J.C. Bosse Y. Laviolette M. Hao K. Nickle D.C. et al.Lung expression quantitative trait loci data set identifies important functional polymorphisms in the asthma-associated IL1RL1 region.J Allergy Clin Immunol. 2014; 134: 729-731Abstract Full Text Full Text PDF PubMed Google Scholar BATF as a possible therapeutic target in asthmatic patientsUbel et al25Ubel C. Sopel N. Graser A. Hildner K. Reinhardt C. Zimmermann T. et al.The activating protein 1 transcription factor basic leucine zipper transcription factor, ATF-like (BATF), regulates lymphocyte- and mast cell-driven immune responses in the setting of allergic asthma.J Allergy Clin Immunol. 2014; 133 (e1-9): 198-206Abstract Full Text Full Text PDF PubMed Google Scholar MicroRNA 9 regulates glucocorticoid signaling in steroid-resistant airway hyperresponsivenessLi et al28Li J.J. Tay H.L. Maltby S. Xiang Y. Eyers F. Hatchwell L. et al.MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by reducing protein phosphatase 2A activity.J Allergy Clin Immunol. 2015; 136: 462-473Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarEosinophilia Improved treatment focusing on EoEWen et al,29Wen T. Stucke E.M. Grotjan T.M. Kemme K.A. Abonia J.P. Putnam P.E. et al.Molecular diagnosis of eosinophilic esophagitis by gene expression profiling.Gastroenterology. 2013; 145: 1289-1299Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar Rothenberg et al30Rothenberg M.E. Wen T. Greenberg A. Alpan O. Enav B. Hirano I. et al.Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis.J Allergy Clin Immunol. 2015; 135: 500-507Abstract Full Text Full Text PDF PubMed Google Scholar Mucin proteins regulate eosinophil survivalIlmarinen et al31Ilmarinen P. Moilanen E. Erjefalt J.S. Kankaanranta H. The polyamine spermine promotes survival and activation of human eosinophils.J Allergy Clin Immunol. 2015; 136: 482-484.e11Abstract Full Text Full Text PDF PubMed Scopus (0) Google ScholarAllergen immunotherapy ICON consensus on AITJutel et al32Jutel M. Agache I. Bonini S. Burks A.W. Calderon M. Canonica W. et al.International consensus on allergy immunotherapy.J Allergy Clin Immunol. 2015; 136: 556-568Abstract Full Text Full Text PDF PubMed Scopus (95) Google Scholar Treg cells achieve allergen tolerance and suppress airway inflammationTsai et al,34Tsai Y.G. Lai J.C. Yang K.D. Hung C.H. Yeh Y.J. Lin C.Y. Enhanced CD46-induced regulatory T cells suppress allergic inflammation after Dermatophagoides pteronyssinus-specific immunotherapy.J Allergy Clin Immunol. 2014; 134: 1206-1209.e1Abstract Full Text Full Text PDF PubMed Google Scholar Akdis and Akdis33Akdis M. Akdis C.A. Mechanisms of allergen-specific immunotherapy: multiple suppressor factors at work in immune tolerance to allergens.J Allergy Clin Immunol. 2014; 133: 621-631Abstract Full Text Full Text PDF PubMed Scopus (165) Google Scholar IL-10–overexpressing B cells and histamine exerts immune regulatory functionsStanic et al,35Stanic B. van de Veen W. Wirz O.F. Ruckert B. Morita H. Sollner S. et al.IL-10-overexpressing B cells regulate innate and adaptive immune responses.J Allergy Clin Immunol. 2015; 135: 771-780.e8Abstract Full Text Full Text PDF PubMed Google Scholar Ferstl et al36Ferstl R. Frei R. Schiavi E. Konieczna P. Barcik W. Ziegler M. et al.Histamine receptor 2 is a key influence in immune responses to intestinal histamine-secreting microbes.J Allergy Clin Immunol. 2014; 134: 744-746.e3Abstract Full Text Full Text PDF PubMed Google Scholar Novel method to monitor the response to immunotherapyShamji et al37Shamji M.H. Layhadi J.A. Scadding G.W. Cheung D.K. Calderon M.A. Turka L.A. et al.Basophil expression of diamine oxidase: a novel biomarker of allergen immunotherapy response.J Allergy Clin Immunol. 2015; 135: 913-921.e9Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar Open table in a new tab An increase in the prevalence of anaphylaxis has been reported in several studies. In a US-wide survey of physicians, an analysis of "Anaphylaxis in America" summarized results from data gathered from experience, knowledge, and attitudes among allergy/immunology specialists, primary care, and emergency physicians.1Altman A.M. Camargo Jr., C.A. Simons F.E. Lieberman P. Sampson H.A. Schwartz L.B. et al.Anaphylaxis in America: a national physician survey.J Allergy Clin Immunol. 2015; 135: 830-833Abstract Full Text Full Text PDF PubMed Google Scholar More pediatric allergy/immunology specialists than others believed that life-threatening allergic reactions today are more common than 10 years ago. Data from national databases concerning anaphylaxis in England and Wales (1992-2012) showed increased incidence but not for fatal anaphylaxis. They also identified marked differences in the age distribution of anaphylaxis admissions and fatalities according to the trigger, which might offer important clues to the underlying pathophysiology.2Turner P.J. Gowland M.H. Sharma V. Ierodiakonou D. Harper N. Garcez T. et al.Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992-2012.J Allergy Clin Immunol. 2015; 135: 956-963.e1Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Studies performed in an Australian hospital focusing on a population with food-related anaphylaxis showed an increase from 5.6-fold in 2005-2006 to 8.2-fold in 2011-2012. The highest rates occurred in children aged 0 to 4 years, but the greatest proportional increase occurred in those aged 5 to 14 years.3Mullins R.J. Dear K.B. Tang M.L. Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012.J Allergy Clin Immunol. 2015; 136: 367-375Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Acceleration in the rate of increase in food-related anaphylaxis in older children and teenagers has implications for management of food allergy patients who are at greatest risk of fatal anaphylaxis.3Mullins R.J. Dear K.B. Tang M.L. Time trends in Australian hospital anaphylaxis admissions in 1998-1999 to 2011-2012.J Allergy Clin Immunol. 2015; 136: 367-375Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Another study also showed an increased rate of hospitalization (from 2001 to 2011) for food-induced anaphylaxis in Italian children.4Nocerino R. Leone L. Cosenza L. Berni Canani R. Increasing rate of hospitalizations for food-induced anaphylaxis in Italian children: an analysis of the Italian Ministry of Health database.J Allergy Clin Immunol. 2015; 135: 833-835.e3Abstract Full Text Full Text PDF PubMed Google Scholar In addition, the prevalence of anaphylaxis was reported to be increasing in the European pediatric population, as well as in the United States and Australia.38Sicherer S.H. Leung D.Y. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014.J Allergy Clin Immunol. 2015; 135: 357-367Abstract Full Text Full Text PDF PubMed Google Scholar Consequently, molecular research on mechanisms of anaphylaxis have been revisited and increased. Tryptase and histamine levels reportedly increase during anaphylaxis but seem to be inadequate to fully identify all anaphylactic responses. Accordingly, Gill et al39Gill P. Jindal N.L. Jagdis A. Vadas P. Platelets in the immune response: revisiting platelet-activating factor in anaphylaxis.J Allergy Clin Immunol. 2015; 135: 1424-1432Abstract Full Text Full Text PDF PubMed Google Scholar reviewed the role of platelet-activating factor (PAF) in anaphylaxis. Patients with acute allergic reactions have very high serum PAF levels, which correla
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