Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec;74(12):2293-2311.
doi: 10.1111/all.13851. Epub 2019 Jun 4.

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Heimo Breiteneder  1 , Zuzana Diamant  2   3 , Thomas Eiwegger  4   5   6 , Wytske J Fokkens  7 , Claudia Traidl-Hoffmann  8   9 , Kari Nadeau  10 , Robyn E O'Hehir  11   12 , Liam O'Mahony  13 , Oliver Pfaar  14 , Maria J Torres  15 , De Yun Wang  16 , Luo Zhang  17 , Cezmi A Akdis  9   18
Affiliations
Review

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Heimo Breiteneder et al. Allergy. 2019 Dec.

Abstract

The specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules. This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring of allergic diseases, asthma, allergic and nonallergic rhinitis, and new approaches to the diagnosis and treatment of drug hypersensitivity reactions are discussed in further detail. In the third section, unmet needs and future research areas for the treatment of allergic diseases are highlighted with topics on food allergy, biologics, small molecules, and novel therapeutic concepts in allergen-specific immunotherapy for airway disease. Unknowns and future research needs are discussed at the end of each subsection.

Keywords: allergy; exposome; microbiome; neuroimmune; respiratory viral infections.

PubMed Disclaimer

Conflict of interest statement

Author ZD reports personal fees from Aquilon, ALK, AstraZeneca, Boehringer Ingelheim, Gilead Hal Allergy, MSD, and Sanofi‐Genzyme, during the conduct of the study. Apart from academic affiliations, ZD works at a phase I/II unit performing clinical studies for different biotech and pharma companies. Author TE reports other from DBV, grants from the Innovation fund Denmark, outside the submitted work; TE is the Co‐I or scientific lead in three investigator‐initiated oral immunotherapy trials supported by the Allergy and Anaphylaxis Program Sickkids. Author KN reports personal fees from Regeneron, grants from NIAID, FARE, and EAT, outside the submitted work; other from Novartis, Sanofi, Astellas, Nestle, BeforeBrands, Alladapt, ForTra, Genentech, AImmune Therapeutics, and DBV Technologies, outside the submitted work. Author REO’H reports other potential financial activities from Aravax Pty Ltd and Paranta Bio Pty Ltd, outside the submitted work. Author OP reports personal fees from Novartis Pharma, MEDA Pharma, Mobile Chamber Experts (a GA2LEN Partner), Pohl‐Boskamp, Indoor Biotechnologies, and Astellas Pharma Global, outside the submitted work; grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, and Anergis S.A., outside the submitted work; grants from Biomay, Nuvo, Circassia, and Glaxo Smith Kline, outside the submitted work. Author CAA reports grants from Allergopharma, Idorsia, Scibase, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission’s Horison's 2020 Framework Programme, Cure, advisory board of Sanofi‐Aventis/Regeneron, grants from Novartis Research Institutes, and Astra Zeneca, outside the submitted work. Authors HB, WF, LO’M, MJT, CTH, DYW, and LZ report no conflicts of interest in relation to this work.

Figures

Figure 1
Figure 1
Molecular mechanisms in allergic inflammation. Epithelial leakiness and activation and their proinflammatory cytokine and chemokine (TNF‐α, IL‐13, TSLP, IL‐25, IL‐33) production induce inflammation and contribute to the Th2 response. Highly activated epithelial cells undergo apoptosis and shedding takes place. Chemokines are essential players for the recruitment of inflammatory cells followed by survival and reactivation of migrating inflammatory cells and their interaction with resident tissue cells and other inflammatory cells. Innate lymphoid cells (ILC2) play a role in T‐ and B‐cell activation and recruitment and are early providers of type 2 cytokines and T‐cell recruitment‐related chemokines. The Th2 type of an immune microenvironment is characterized by IL‐4, IL‐5, IL‐9, IL‐13, IL‐25, IL‐33 production by Th2 cells, ILCs, mast cells, and tissue cells. Eosinophilia is induced by IL‐5, IL‐25, and IL‐33. Local and systemic IgE production takes place in allergic patients with the involvement of IL‐4 and IL‐13. Other effector T‐cell subsets, such as Th9, Th17, and Th22 cells, also play partial roles in inflammation, mucus production, and tissue healing. Smooth muscle, myofibroblast activation, and bronchial hyperreactivity are related to IL‐4, IL‐9, IL‐13, IL‐25, and IL‐33. Several chemokines, and arachidonic acid pathway molecules and other small molecules play roles in the inflammatory cell recruitment and further augmentation of the inflammatory cascades. Treg and Breg cells play a role on control of inflammation and extensive cellular activation by using IL‐10 and TGF‐β as well as many other suppressive mechanisms
Figure 2
Figure 2
The exposome: The exposome includes the entire environmental exposures of an individual from conception throughout the whole life. Early‐life events such as mode of delivery, breastfeeding, mother's diet, lifestyle and health status, antibiotics, and other drug usage in pregnancy and early childhood, early‐life environment (ie, siblings, pets at home, proximity to farm animals and green areas, usage of primary farm products) can significantly influence the epigenetic regulation of immune system and tissue cells
Figure 3
Figure 3
Precision medicine: Precision medicine requires the network of knowledge from both biomedical and clinical research. It includes all of the omics areas and exposome from molecular characterization and biomarker development to electronic health records, and clinical discoveries in diagnosis and treatment. The introduction of a new taxonomy is needed to ensure that all the stakeholders speak the same language
Figure 4
Figure 4
Omics: The omics revolution was one of the major driving forces of recent developments that enabled investigation of almost everything at the molecular level of proteins, lipids, and small molecules including innumerable DNA and RNA sequencings with a hypothesis‐free approach
See this image and copyright information in PMC

References

    1. Rondon C, Blanca‐Lopez N, Campo P, et al. Specific immunotherapy in local allergic rhinitis: a randomized, double‐blind placebo‐controlled trial with Phleum pratense subcutaneous allergen immunotherapy. Allergy. 2018;73(4):905‐915. - PubMed
    1. Eckl‐Dorna J, Fröschl R, Lupinek C, et al. Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels‐A pilot study. Allergy. 2018;73(5):1003‐1012. - PMC - PubMed
    1. Boligan KF, von Gunten S. Innate lymphoid cells in asthma: cannabinoids on the balance. Allergy. 2017;72(6):839‐841. - PubMed
    1. Terl M, Sedlák V, Cap P, et al. Asthma management: a new phenotype‐based approach using presence of eosinophilia and allergy. Allergy. 2017;72(9):1279‐1287. - PubMed
    1. Casale TB, Chipps BE, Rosén K, et al. Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma. Allergy. 2018;73(2):490‐497. - PMC - PubMed

Publication types