Mechanism of Action of Allergen Immunotherapy

Şahin, Ethem; Bafaqeeh, Sameer Ali; Güven, Selis Gülseven; Çetinkaya, Erdem Atalay; Muluk, Nuray Bayar; Çoşkun, Zerrin Özergin; Лопатин, А С; Kar, Murat; Pınarbaşlı, Mehmet Özgür; Cingi, Cemal

doi:10.2500/ajra.2016.30.4367

Cited by 31 publications

(32 citation statements)

References 45 publications

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“…On the other hand, the conditioning of allergic responses to the environmental context, as well as its dependency on sleep, might be exploited to develop and refine antiallergic treatments. Allergen immunotherapy is based on the relearning of an appropriate immune response to an allergen (35) and may profit from sleep in the same way as exposure therapy of fears does (36), especially when including multiple-context exposures (37). Ultimately, this study might provide new perspectives in the understanding of other immunerelated medical conditions that are receptive to psychological influences and thus also might be affected by sleep-dependent learning processes (38)(39)(40).…”

Section: Discussionmentioning

confidence: 96%

Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure

Besedovsky

Benischke

Fischer

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Allergies are highly prevalent, and allergic responses can be triggered even in the absence of allergens due to Pavlovian conditioning to a specific cue. Here we show in humans suffering from allergic rhinitis that merely reencountering the environmental context in which an allergen was administered a week earlier is sufficient to trigger an allergic response—but only if participants had slept after allergen exposure. This context-conditioning effect was entirely absent when participants stayed awake the night after allergen exposure or were tested in a different context. Unlike in context conditioning, cue conditioning (to an odor stimulus) occurred independently of sleep, a differential pattern that is likewise observed for conditioning in the behavioral domain. Our findings provide evidence that allergic responses can be conditioned to contextual information alone, even after only a single-trial conditioning procedure, and that sleep is necessary to consolidate this rapidly acquired maladaptive response. The results unravel a mechanism that could explain part of the strong psychological impact on allergic responses.

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Section: Discussionmentioning

confidence: 96%

Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure

Besedovsky

Benischke

Fischer

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…However, little is known about how to reverse the Treg defect in patients with AR. Increasing evidence from basic and clinical research has revealed the limitations, disadvantages, and risks of inducing and/or expanding Tregs by SIT or the adoptive transfer of exogenous Treg, so it is necessary to explore new therapeutic targets for AR immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Both Tregs maintain immunosuppressive activity in the inflammatory microenvironment and may prevent AADs . However, induction of endogenous Tregs by allergen‐specific immunotherapy (SIT) and the adoptive transfer of exogenous Tregs have a number of limitations and fatal risks, such as functional insufficiency and severe systemic side effects…”

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confidence: 99%

Adoptive cell therapy of tolerogenic dendritic cells as inducer of regulatory T cells in allergic rhinitis

Sun

Wei

et al. 2018

Int Forum Allergy Rhinol

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Background Regulatory T cells (Tregs) have become promising candidates for immunotherapy in allergic rhinitis (AR). The contributing role of tolerogenic dendritic cells (tDCs) in the augmentation of Tregs in AR remains to be determined. Methods The properties of tDCs in expanding Tregs and their potential to ameliorate AR were evaluated in vitro and in vivo. Results Monocyte‐derived tDCs stimulated with Dermatophagoides pteronyssinus allergen 1 favored the generation of activated Tregs (aTregs) and suppressed effector T‐cell responses in a transforming growth factor‐beta/interleukin‐10 (TGF‐β/IL‐10)‐dependent manner in vitro. The adoptive transfer of tDCs inhibited allergic airway inflammation in the mouse model, whereas depletion of CD25+ cells or blocking TGF‐β/IL‐10 signaling eliminated the inhibitory effect, indicating that Tregs were involved in the anti‐inflammatory activity of tDCs. Conclusion Our data show that tDCs are a potential therapeutic target in AR.

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“…These immunologic effects of AIT result in a long-lasting tolerance to the specific allergen, by decreasing the number and the activation of eosinophils and mast cells, and modulating the response and the activity of T and B cells, reducing the production and the release of IgE while increasing IgG4, a subclass of blocking antibody which compete with IgE for binding with the allergens, causing the reduction in activation of basophils and B cells. Although routes, doses of allergen and site of administration differ between SLIT and SCIT, the final effect in the modulation of the immune network is the same: the induction of peripheral tolerance mediated by Treg, which modulates the activation and the survival of peripheral immune cells by the release of anti-inflammatory cytokines such as IL-10 with suppression of IgE production and inhibition of B cells proliferation (50). Figure 1 summarizes the main mechanisms of action if SCIT and SLIT.…”

Section: Immunological Mechanisms Of Aitmentioning

confidence: 99%

Subcutaneous and sublingual allergen-specific immunotherapy: a tale of two routes

Incorvaia

Ciprandi

Nizi

et al. 2020

Eur Ann Allergy Clin Immunol

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Specific immunotherapy is the only treatment acting on the causes and not only on symptoms of respiratory allergy. It was first introduced as subcutaneous immunotherapy (SCIT) with the aim to induce immunological tolerance to the administered allergen(s). In the 1980s, sublingual immunotherapy (SLIT) was developed, mainly to improve the safety, which was a critical issue at that time. This article reviewed the available literature, including a large number of randomized controlled trials, meta-analyses, and real-life studies as well, on the outcomes of SCIT and SLIT concerning the treatment critical issues of the two routes, that are efficacy, safety, cost-effectiveness, and compliance to treatment. The efficacy of SCIT and SLIT is similar in respiratory allergy, providing, based on the induction of typical changes in the immunologic response, an early control of symptoms that steadily increases during the treatment and its efficacy lasts after the recommended duration of three years. Such results are the reason why SCIT and SLIT have economic advantage over symptomatic drugs. ated more than a century ago as a merely empirical treatment of hay fever (6), while SLIT was introduced only in the 1980s, when the knowledge on pathophysiology of allergy and mechanisms of AIT became clear (7). In this review, meta-analyses were preferred to evaluate the effectiveness and safety of SCIT and SLIT, while large-scale trials performed for registration from the regulatory agencies were used for the latest generation of SLIT products. Also real-life studies on very large patients population were considered. The milestones in the development of allergen immunotherapy The injective route was introduced in 1911 although the pathogenesis of allergic disease was not fully elucidated until the discovery of IgE antibodies in the 1960s (8), which clarified the mechanisms of allergy and the immunologic modifications achieved with AIT (9,10). Despite this, safety issues emerged in the 1980s, when fatal reactions to SCIT from the UK (11) and USA (12) were described. Nowadays it has been clarified that

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Mechanism of Action of Allergen Immunotherapy

Cited by 31 publications

References 45 publications

Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure

Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure

Adoptive cell therapy of tolerogenic dendritic cells as inducer of regulatory T cells in allergic rhinitis

Subcutaneous and sublingual allergen-specific immunotherapy: a tale of two routes

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