Original Articles: Allergen-Specific Immunotherapy and Biologics
Allergen-specific immunotherapy (AIT) and biologics represent two significant advancements in the treatment of allergic diseases. AIT works by desensitizing or tolerazing the immune system to specific allergens, reducing allergic reactions over time. It is commonly used to treat allergic rhinitis, allergic asthma, and stinging insect allergies. Biologics, on the other hand, are a newer class of medications that target specific molecules involved in the allergic response, providing targeted and often more effective treatment for conditions like asthma, atopic dermatitis, and chronic urticaria.
In recent years, there has been a growing interest in both AIT and biologics as effective treatment options for allergic diseases. Clinical studies have demonstrated their efficacy in improving symptoms and quality of life for patients with various allergic conditions. Furthermore, the development of new biologics and the refinement of AIT techniques continue to expand treatment options for patients worldwide.
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112 Articles |
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Modulation of Cellular, Molecular, and Humoral Responses by PQ Grass 27,600 SU for the Treatment of Seasonal Allergic Rhinitis: A Randomised Double Blind Placebo Control Exploratory Field Study
J. A. Layhadi, S. Starchenka, P.-J. De Kam, et al. Allergy. First published: 08 July 2025
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Oral Immunotherapy in Peanut-Allergic Adults Using Real-World Materials
Hunter, H., Ue, K.L., Cornelius, V., et al. Allergy. First published: 23 April 2025
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Immunological In Vitro Assay for Quantification of Adjuvanted Allergoids
Schlünder, S., Echternach, J., Bartel, D., et al. Allergy. First published: 31 March 2025
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Recombinant Hypoallergenic Cat Allergy Vaccines
Trifonova, D., Curin, M., Focke-Tejkl, M., et al. Allergy. First published: 03 April 2025
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Correlation Between N-Glycan GnGnXF3 and the Allergic Immune Response Against Juniperus ashei Pollen
Álvarez, J., Parody, N., Calzada, D., et al. Allergy. First published: 06 February 2025
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Six Injections of Modified Adjuvanted PQ Grass Is Effective and Well-Tolerated in a Pivotal Phase III Trial
Zielen, S., Bernstein, J.A., Sturm, G.J., et al. Allergy. First published: 04 February 2025
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Allergen Specific IgE is a Stronger Predictor of Remission Following Peanut Oral Immunotherapy Than Age in Children Aged 1–10 Years
Ashley, S.E., Lloyd, M., Loke, P., et al. Allergy. First published: 26 December 2024
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Short-course subcutaneous treatment with birch pollen allergoids greatly improves symptom and medication scores in birch allergy
Mösges R, Raskopf E, Klimek L, et al. Allergy. First published: 09 November 2024
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One-strength dose escalation of house dust mite depot product for subcutaneous immunotherapy is safe and tolerable
Jutel M, Vogelberg C, Duwensee K, et al. Allergy. First published: 14 November 2024
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Improved quality control of allergen products: Assessing the molecular allergen composition by mass spectrometry
Augustin S, Eichhorn T, Wald M, et al. Allergy. First published: 24 October 2024
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The SQ tree sublingual immunotherapy tablet is effective and well tolerated in children—A pivotal phase III trial
Gappa M, Gagnon R, Horak F, et al. Allergy. First published: 04 November 2024
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Cross-protection of AIT-induced antibodies to related allergens requires a high degree of structural identity
Demir H, Radauer C, Strobl MR, et al. Allergy. First published: 23 September 2024
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Allergen immunotherapy adverse events in adults with respiratory allergies-data from ADER: An EAACI task force report
Allergy. First published: 22 August 2024
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IL-10-modulated dendritic cells from birch pollen- and hazelnut-allergic patients facilitate Treg-mediated allergen-specific and cross-reactive tolerance
Heinl PV, Graulich E, Weigmann B, et al. Allergy. First published: 28 July 2024
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How to hit the allergy target: A critical appraisal of intralymphatic immunotherapy with practical recommendations on ultrasound-guided injections
Flory S, Hviid-Vyff B, Šošić L, et al. Allergy. First published: 07 May 2024
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Generation of a virus-like particles based vaccine against IgE
Gharailoo Z, Plattner K, Augusto G, et al. Allergy. First published: 01 March 2024
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House dust mite SCIT reduces asthma risk and significantly improves long-term rhinitis and asthma control—A RWE study
Jutel M, Klimek L, Richter H, Brüggenjürgen B, Vogelberg C. Allergy. First published: 02 March 2024
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The effectiveness of pollen allergen immunotherapy on allergic rhinitis over 18 years: A national cohort study in Denmark
Bager P, Poulsen G, Wohlfahrt J, Melbye M. Allergy. First published: 21 January 2024
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Quantifying the benefits of early sublingual allergen immunotherapy tablet initiation in children
Hamelmann E, Hammerby E, Scharling KS, et al. Allergy. First published: 26 December 2023
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Phase 1 trial supports safety and mechanism of action of peptide immunotherapy for peanut allergy
Voskamp AL, Khosa S, Phan T, et al. Allergy. First published: 19 December 2023
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Safety and immunopharmacology of ASP0892 in adults or adolescents with peanut allergy: two randomized trials
Ferslew BC, Smulders R, Zhu T, et al. Allergy. First published: 27 November 2023
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A randomized, double-blind, placebo-controlled trial with mannan-conjugated birch pollen allergoids
Mösges R, Zeyen C, Raskopf E, et al. Allergy. First published: 12 October 2023
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Recombinant PreS-fusion protein vaccine for birch pollen and apple allergy
Khaitov M, Shilovskiy I, Valenta R, et al. Allergy. First published: 19 October 2023
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Influence of antigen density and TLR ligands on preclinical efficacy of a VLP-based vaccine against peanut allergy
Krenger PS, Josi R, Sobczak J, et al. Allergy. First published: 10 October 2023
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Patient-level indirect treatment comparison of lanadelumab versus pdC1-INH i.v. in hereditary angioedema patients: PATCH study
Magerl, M, Schiffhorst, G, Fanter, L, et al. Allergy. First published: 29 August 2023
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Short-course subcutaneous treatment with PQ Grass strongly improves symptom and medication scores in grass allergy
de Kam, PJ, Zielen, S, Bernstein, JA, et al. Allergy. First published: 27 June 2023
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Adherence and persistence in allergen immunotherapy (APAIT): a reporting checklist for retrospective studies
Pfaar, O., Devillier, P., Schmitt, J., et al. Allergy. First published: 27 March 2023
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Immune Response Evolution in Peanut Epicutaneous Immunotherapy for Peanut-Allergic Children
Bastin, M., Carr, W.W., Davis, C.M., et al. Allergy. First published: 14 March 2023
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The next generation virus-like particle platform for the treatment of peanut allergy
Sobczak, J.M., Krenger, P.S., Storni, F., et al. Allergy. First published: 08 March 2023
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Targeting Ara h 2 with human-derived monoclonal antibodies prevents peanut-induced anaphylaxis in mice
Paolucci, M., Wuillemin, N., Homère, V., et al. Allergy. First published: 27 January 2023
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Anti-kit antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria
Terhorst-Molawi, D., Hawro, T., Grekowitz, E., et al. Allergy. First published: 16 November 2022
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Comprehensive analysis of human IL-4 receptor subunits shows compartmentalization in steady state and dupilumab treatment
Heeb, LEM, Boyman, O. Allergy. First published: 05 November 2022
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Ligelizumab impairs IgE-binding to plasmacytoid dendritic cells more potently than omalizumab and restores IFN-α production and FOXP3+ Treg generation
Benito-Villalvilla, C., de la Rocha-Muñoz, A., López-Abente, J., et al. Allergy. First published: 31 October 2022
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Scalp biomarkers during dupilumab treatment support Th2 pathway pathogenicity in alopecia areata
Renert-Yuval, Y., Pavel, A.B., Del Duca, E., et al. Allergy. First published: 22 October 2022
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Stimulation of naïve B cells with a fusion protein consisting of FlaA and Bet v 1 induces regulatory B cells ex vivo
Goretzki, A., Lin, Y.-J., Meier, C., et al. Allergy. First published: 04 October 2022
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Efficacy and safety of food allergy oral immunotherapy in adults
Epstein-Rigbi, N., Levy, M.B., Nachshon, L., et al. Allergy. First published: 03 October 2022
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Predicting dupilumab treatment outcome in patients with primary diffuse type 2 chronic rhinosinusitis
Soyka, M.B., Ryser, F.S., Brühlmann, C., et al. Allergy. First published: 26 September 2022
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RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: two unique cell fates and CD29 as a biomarker for treatment effect
McKenzie, C.I., Varese, N., Aui, P.M., et al. Allergy. First published: 25 September 2022
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Long-term changes in milk component immunoglobulins reflect milk oral immunotherapy outcomes in Finnish children
Kauppila, TK, Hinkkanen, V, Savinko, T, et al. Allergy. First published: 15 August 2022
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Dupilumab reduced impact of severe exacerbations on lung function in patients with moderate-to-severe type 2 asthma
Papi, A., Corren, J., Castro, M., et al. Allergy. First published: 28 July 2022
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Patient-centered dupilumab dosing regimen leads to successful dose reduction in persistently controlled atopic dermatitis
Spekhorst, L.S., Bakker, D., Drylewicz, J., et al. Allergy. First published: 15 July 2022
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Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): in-depth sinus surgery analysis
Fokkens, W.J., Mullol, J., Kennedy, D., et al. Allergy. First published: 13 July 2022
Dupilumab significantly improves skin barrier function in patients with moderate-to-severe atopic dermatitis
Berdyshev, E., Goleva, E., Bissonnette, R., et al. Allergy. First published: 11 July 2022
A recombinant multimeric dog allergen prevents airway hyperresponsiveness in a model of asthma marked by vigorous TH2 and TH17 cell responses
Stark, J.M., Liu, J., Tibbitt, C.A., et al. Allergy. First published: 03 June 2022
Remission of peanut allergy is associated with rewiring of allergen-driven T helper 2-related gene networks
Ashley, SE, Jones, AC, Anderson, D, et al. Allergy. First published: 27 May 2022
First-in-human phase 2 trial with mite allergoids coupled to mannan in subcutaneous and sublingual immunotherapy
Nieto, A., Mazón, Á., Nieto, M., et al. Allergy. First published: 16 May 2022
Comparison of rhinitis treatments using MASK-air® data and considering the minimal important difference
Sousa-Pinto, B., Schünemann, H.J., Sá-Sousa, A., et al. Allergy. First published: 14 May 2022
Cost-effectiveness analysis of house dust mite allergen immunotherapy in children with allergic asthma
Farraia, M., Paciência, I., Mendes, F.C., et al. Allergy. First published: 22 April 2022
Psychometric parameters of food allergy quality of life during an allergen immunotherapy trial
Lins de Holanda Coelho, G., DunnGalvin, A., Greenhawt, M., et al. Allergy. First published: 25 April 2022
Molecular reactivity profiling upon immunotherapy with a 300 IR sublingual house dust mite tablet reveals marked humoral changes towards major allergens
Potapova, E., Bordas-Le Floch, V., Schlederer, T., et al. Allergy. First published: 26 April 2022
Allergen Immunotherapy for asthma prevention: a systematic review and meta-analysis of randomised and non-randomised controlled studies
Farraia, M., Paciência, I., Mendes, F.C., et al. Allergy. First published: 28 March 2022
The anti-KIT monoclonal antibody CDX-0159 induces profound and durable mast cell suppression in a healthy volunteer study
Alvarado, D., Maurer, M., Gedrich, R., et al. Allergy. First published: 19 February 2022
Dupilumab improves health-related quality of life in severe chronic rhinosinusitis with nasal polyps
Lee, S.E., Hopkins, C., Mullol, J. et al. Allergy. First published: 16 January 2022
A phase 2, randomized multi oral immunotherapy with omalizumab ‘real life’ study
Sindher, S.B., Kumar, D., Cao, S., et al. Allergy. First published: 11 January 2022
Cashew oral immunotherapy for desensitizing cashew-pistachio allergy (Nut CRACKER study)
Elizur, A., Appel, M.Y., Nachshon, L., et al. Allergy. First published: 09 January 2022
Allergen immunotherapy and/or biologicals for IgE-mediated food allergy: systematic review and meta-analysis
de Silva, D., Rodríguez del Río, P., de Jong, N.W., et al. Allergy. First published: 09 January 2022
Determining the minimal important differences in the RQLQ score with grass and tree allergy immunotherapy versus placebo in adults with moderate-to-severe allergy
Blaiss, M.S., Juhl, R.G., Siew, L.Q., et al. Allergy. First published: 05 January 2022
Baseline type 2 biomarker levels and response to tezepelumab in severe asthma
Corren, J., Pham, T.-H., Gil, E.G., et al. Allergy. First published: 16 December 2021
Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: A one-year extension study
Maurer, M, Giménez-Arnau, A, Bernstein, JA, et al. Allergy. First published: 13 November 2021
A three-stage design for allergen immunotherapy trials
Tang, X., Rabin, R.L., Yan, L.K. Allergy. First published: 02 October 2021
Regulatory roles of three miRNAs on allergen mRNA expression in Tyrophagus putrescentiae
Zhou, Y., Li, Q., Pan, R., et al. Allergy. First published: 27 September 2021
Coordinated IgG2 and IgE responses as a marker of allergen immunotherapy efficacy
Bordas-Le Floch, V, Berjont, N, Batard, T, et al. Allergy. First published: 22 September 2021
Development and preclinical evaluation of virus-like particle vaccine against COVID-19 infection
Yilmaz, IC, Ipekoglu, EM, Bulbul, A, et al. Allergy. First published: 14 September 2021
Phase 2a randomized clinical trial of dupilumab (anti-IL-4Rα) for alopecia areata patients
Guttman-Yassky, E, Renert-Yuval, Y, Bares, J, et al. Allergy. First published: 30 August 2021
Efficacy and safety of dupilumab in patients with uncontrolled severe CRSwNP and a clinical diagnosis of NSAID-ERD: Results from two randomized placebo-controlled phase 3 trials
Mullol, J., Laidlaw, T.M., Bachert, C., et al. Allergy. First published: 30 August 2021
High dose pollen intralymphatic immunotherapy: Two RDBPC trials question the benefit of dose increase
Hellkvist, L, Hjalmarsson, E, Weinfeld, D, et al. Allergy. First published: 11 August 2021
Long-term prevention of hereditary angioedema attacks with lanadelumab: the HELP OLE Study
Banerji, A., Bernstein, J.A., Johnston, D.T., et al. Allergy. First published: 21 July 2021
Immunological effects of adjuvanted low-dose allergoid allergen-specific immunotherapy in experimental murine house dust mite allergy
Heldner, A., Alessandrini, F., Russkamp, D., et al. Allergy. First published: 20 July 2021
Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status
Fujieda, S, Matsune, S, Takeno, S, et al.Allergy. First published: 16 May 2021
Benralizumab improves symptoms of patients with severe, eosinophilic asthma with a diagnosis of nasal polyposis
Canonica, G.W., Harrison, T.W., Chanez, P., et al. Allergy. First published: 12 May 2021
Standardisation of allergen products: 4. Validation of a candidate European pharmacopoeia standard method for quantification of major grass pollen allergen Phl p 5
Wang, S.-H., Zissler, U.M., Buettner, M., et al. Allergy. First published: 09 May 2021
RNA viruses in the house dust mite dermatophagoidespteronyssinus, detection in environmental samples and in commercial allergen extracts used for in vivo diagnosis
Vidal-Quist, J.C., Vidal, C., Escolar, F., Lambrecht, B.N., Rombauts, S. and Hernández-Crespo, P.Allergy. First published: 29 April 2021
Safety of the standardized quality tree sublingual immunotherapy tablet: Pooled safety analysis of clinical trials
Biedermann, T., Couroux, P., Greve, T.M. and Mäkelä, M. Allergy. First published: 27 April 2021
A mathematical model to identify optimal combinations of drug targets for dupilumab poor responders in atopic dermatitis
Miyano, T., Irvine, A.D. and Tanaka, R.J. Allergy.First published: 24 April 2021
Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic
Yeğit, O.O., Demir, S., Ünal, D., et al. Allergy. First published: 27 April 2021
An exhausted phenotype of TH2 cells is primed by allergen exposure, but not reinforced by allergen-specific immunotherapy
Wang, S.-H., Zissler, U.M., Buettner, M., et al. Allergy. 2021; 76: 2827-2839
Immune changes beyond Th2 pathways during rapid multifood immunotherapy enabled with omalizumab
Manohar, M., Dunham, D., Gupta, S., et al. Allergy. 2021; 76: 2809-2826
Low-affinity but high-avidity interactions may offer an explanation for IgE-mediated allergen cross-reactivity
Chang, X, Zha, L, Wallimann, A, et al. Allergy. 2021; 76: 2565– 2574
IgE-cross-blocking antibodies to fagales following sublingual immunotherapy with recombinant Bet v 1
Grilo, J.R., Kitzmüller, C., Aglas, et al. Allergy.2021; 76: 2555-2564
Allergen-specific immunotherapy induces the suppressive secretoglobin 1A1 in cells of the lower airways
Zissler, U.M., Jakwerth, C.A., Guerth, F., et al. Allergy.2021; 76: 2461-2474
β-blockers and ACE inhibitors are not a risk factor for severe systemic sting reactions and adverse events during venom immunotherapy
Sturm, G.J., Herzog, S.A., Aberer, W., et al. Allergy.2021; 76: 2166-2176
Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1-specific immunotherapy using high-dose CpG adjuvant
Leonard, C., Montamat, G., Davril, C., et al. Allergy.2021; 76: 2153-2165
Artemisia annua-sublingual immunotherapy for seasonal allergic rhinitis: A randomized controlled trial
Lou, H, Huang, Y, Ouyang, Y, et al. Allergy. 2020; 75: 2026– 2036
Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial
Ohsawa, I., Honda, D., Suzuki, Y., Allergy.2021; 76: 1789-1799
Exercise-induced allergic reactions on desensitization to wheat after rush oral immunotherapy
Furuta, T, Tanaka, K, Tagami, K, et al. Allergy. 2020; 75: 1414– 1422
Epicutaneous immunotherapy protects cashew-sensitized mice from anaphylaxis
Pelletier, B, Perrin, A, Assoun, N, et al. Allergy. 2021; 76: 1213– 1222
Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics
Barker-Tejeda, TC, Bazire, R, Obeso, D, et al. Allergy. 2021; 76: 1199– 1212
Impact of lanadelumab on health-related quality of life in patients with hereditary angioedema in the HELP study
Lumry, W.R., Weller, K., Magerl, M., et al. Allergy.2021; 76: 1188-1198
Laser-facilitated epicutaneous immunotherapy with hypoallergenic beta-glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma
Korotchenko, E, Schießl, V, Scheiblhofer, S, et al. Allergy. 2021; 76: 210– 222
Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline
Bourdin, A, Papi, AA, Corren, J, et al. Allergy. 2021; 76: 269– 280
Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks
Riedl, MA, Maurer, M, Bernstein, JA, et al. Allergy. 2020; 75: 2879– 2887
Efficacy of dupilumab in atopic comorbidities associated with moderate-to-severe adult atopic dermatitis
Nettis, E, Patella, V, Lombardo, C, et al. Allergy. 2020; 75: 2653– 2661
Quality of life of children aged 8-12 years undergoing food allergy oral immunotherapy: Child and parent perspective
Epstein-Rigbi, N, Goldberg, MR, Levy, MB, Nachshon, L, Elizur, A. et al. Allergy. 2020; 75: 2623– 2632
Real-world evidence of subcutaneous allergoid immunotherapy in house dust mite-induced allergic rhinitis and asthma
Jutel, M, Brüggenjürgen, B, Richter, H, Vogelberg, C. Allergy. 2020; 75: 2050– 2058
Structure of intact IgE and the mechanism of ligelizumab revealed by electron microscopy
Jensen, RK, Jabs, F, Miehe, M, et al. Allergy. 2020; 75: 1956– 1965
Laser-facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation
Korotchenko, E, Moya, R, Scheiblhofer, S, et al.Allergy. 2020; 75: 1217– 1228
CARsomes inhibit airway allergic inflammation in mice by inducing antigen-specific Th2 cell apoptosis
Zhang, H-P, Sun, Y-X, Lin, Z, et al. Allergy. 2020; 75: 1205– 1216
Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation
Le Floc’h, A, Allinne, J, Nagashima, K, et al. Allergy. 2020; 75: 1188– 1204
Induction of IgG(2) and IgG(4) B-cell memory following sublingual immunotherapy for ryegrass pollen allergy
Heeringa, JJ, McKenzie, CI, Varese, N, et al. Allergy. 2020; 75: 1121– 1132
Intranasal nanoemulsion vaccine confers long-lasting immunomodulation and sustained unresponsiveness in a murine model of milk allergy
O'Konek, JJ, Landers, JJ, Janczak, KW, et al. Allergy. 2020; 75: 872– 881
TGFβ1 mimetic peptide modulates immune response to grass pollen allergens in mice
Araujo, GR, Aglas, L, Vaz, ER, et al. Allergy. 2020; 75: 882– 891
Venom immunotherapy in patients with clonal mast cell disorders: IgG4 correlates with protection
Jarkvist, J, Salehi, C, Akin, C, Gülen, T. Allergy. 2020; 75: 169– 177
Dupilumab is very effective in a large cohort of difficult-to-treat adult atopic dermatitis patients: First clinical and biomarker results from the BioDay registry
Ariëns, LFM, van der Schaft, J, Bakker, DS, et al. Allergy. 2020; 75: 116– 126
Alum impairs tolerogenic properties induced by allergoid-mannan conjugates inhibiting mTOR and metabolic reprogramming in human DCs
Benito-Villalvilla, C, Soria, I, Pérez-Diego, M, Fernández-Caldas, E, Subiza, JL, Palomares, O. Allergy. 2020; 75: 648– 659
A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens
Huang, H-J, Curin, M, Banerjee, S, et al. Allergy. 2019; 74: 2461– 2478
Modulation of CRTh2 expression on allergen‐specific T cells following peptide immunotherapy
Rudulier, CD, Tonti, E, James, E, Kwok, WW, Larché, M. Allergy. 2019; 74: 2157– 2166
IL-4 receptor α blockade prevents sensitization and alters acute and long-lasting effects of allergen-specific immunotherapy of murine allergic asthma
Russkamp, D, Aguilar-Pimentel, A, Alessandrini, F, et al. Allergy. 2019; 74: 1549– 1560
The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma
Chapman, KR, Albers, FC, Chipps, B, et al. Allergy. 2019; 74: 1716– 1726
Variability of allergens in commercial fish extracts for skin prick testing
Ruethers, T, Taki, AC, Nugraha, R, et al. Allergy. 2019; 74: 1352– 1363
Chemically modified peanut extract shows increased safety while maintaining immunogenicity
van der Kleij, HPM, Warmenhoven, HJM, van Ree, R, et al.Allergy. 2019; 74: 986– 995
Der p 1-specific regulatory T-cell response during house dust mite allergen immunotherapy
Boonpiyathad, T, Sokolowska, M, Morita, H, et al. Allergy. 2019; 74: 976– 985
Preventive sublingual immunotherapy with house dust mite extract modulates epitope diversity in pre-school children
Ponce, M, Schroeder, F, Bannert, C, et al. Allergy. 2019; 74: 780– 787
Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis
Jonstam, K, Swanson, BN, Mannent, LP, et al. Allergy. 2019; 74: 743– 752