Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Larché, Mark

doi:10.1513/annalsats.201402-090aw

Cited by 33 publications

(36 citation statements)

References 33 publications

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“…Early Fel d 1‐specific T‐cell activation was followed by full T‐cell unresponsiveness to allergen after 1 year in the MAT‐Fel d 1 group, characterized by increased allergen‐specific T regulatory cells, decreased circulating Fel d 1 tetramer‐positive cells, increased IL‐10 and FOXP3 expression, and change in the HR2/HR1 ratio toward HR2 . T‐cell epitope peptide immunotherapy has also significantly improved over the last years and the underlying mechanisms have been better understood …”

Section: Allergen‐specific Immunotherapymentioning

confidence: 99%

Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells

Palomares

Akdiş

Martín‐Fontecha

2017

Immunological Reviews

263

300

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Allergy is a major public health problem with a high socio-economic impact. The number of allergic patients is expected to reach to four billion within two decades when the World's population reaches to 10 billion. Our knowledge on the molecular mechanisms underlying allergic diseases and allergen tolerance induction had significant advances during the last years. Nowadays, it is well accepted that the generation and maintenance of allergen-specific regulatory T cells (Tregs) and regulatory B cells (Bregs) and the involvement of their suppressive cytokines and surface molecules are essential for the induction of allergen tolerance. These mechanisms play essential roles for the restoration of healthy immune responses to allergens in allergen-specific immunotherapy (AIT) and healthy immune response during high-dose antigen exposure in beekeepers and cat owners. AIT remains as the only disease-modifying and curative treatment for allergic diseases and represents a perfect model to investigate the antigen-specific immune responses in humans. A large number of clinical trials demonstrated AIT as an effective treatment in many patients, but it still faces several drawbacks in relation to efficacy, safety, long duration, and patient adherence. Novel strategies to overcome these inconveniences, such as the development of novel adjuvants and alternative routes of administration are being developed. The better understanding of the molecular mechanism governing the generation of Treg and Breg cells during allergen tolerance might well open new avenues for alternative therapeutic interventions in allergic diseases and help better understanding of other immune-tolerance-related diseases.

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Section: Allergen‐specific Immunotherapymentioning

confidence: 99%

Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells

Palomares

Akdiş

Martín‐Fontecha

2017

Immunological Reviews

263

300

View full text Add to dashboard Cite

show abstract

“…179–181 Trials of other peptide therapies related to house dust mite, grass pollen, and ragweed are ongoing. 182,183 Nonetheless, the challenges are considerable in terms of optimizing dosing and selecting those peptide combinations that might prove efficacious within the general population. Indeed, early studies of cat peptides demonstrated their ability to induce a marked decrease in FEV 1 in asthmatic patients with cat allergy several hours after injection.…”

Section: Future Directions and Clinical Implicationsmentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

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Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

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“…Taken together, the results could explain how IgE antibodies are relevant to the process and that locally accumulating T cells could be a target for peptide immunotherapy. 35 …”

Section: Understanding the Role Of Allergens In Asthmatic Patients Anmentioning

confidence: 99%

IgE in the diagnosis and treatment of allergic disease

Platts-Mills

Schuyler

Erwin

et al. 2016

Journal of Allergy and Clinical Immunology

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Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the “allergic” disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow’s milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response.

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Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Cited by 33 publications

References 33 publications

Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells

Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells

Pathogenic CD4 + T cells in patients with asthma

IgE in the diagnosis and treatment of allergic disease

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