Oral immunotherapy with omalizumab reverses the Th2 cell‐like programme of regulatory T cells and restores their function

Abdel-Gadir, Azza; Schneider, Lynda C.; Casini, Arianna; Charbonnier, Louis-Marie; Little, Sara V.; Harrington, Timothy; Umetsu, Dale T.; Rachid, Rima; Chatila, Talal A.

doi:10.1111/cea.13161

Cited by 64 publications

(32 citation statements)

References 40 publications

(99 reference statements)

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“…The subverted TH2‐like Treg cells play a critical role in disease pathogenesis under conditions of TH2‐high inflammation induced, including paradigms of food allergy (FA) and allergic airway inflammation induced in Il4ra F709 mice . A similar phenotype is seen in human subjects with FA, indicating that this subversion is operative in human allergic disorders . A more sharply restricted Treg cell TH2 cell‐like response can aid in providing protection against helminths by generating TH2 cell‐like ex‐Treg cells that add to the TH2 response …”

Section: Il‐4r Signalling In Tolerance Modulationmentioning

confidence: 99%

“…Abdel‐Gadir et al found that treatment of lymphocytes peanut‐allergic patients with anti‐IL‐4Rα mAb augmented the suppressive function of peanut‐reactive Treg cells, highlighting the potential disease‐modifying effect of anti‐IL4 therapy . Recently, Rial MJ et al have presented a case report showing a very successful therapy of newly developed food allergy to corn and nuts using Dupilumab .…”

Section: Dupilumab For Food Allergymentioning

confidence: 99%

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Mechanisms of Dupilumab

Harb

Chatila

2019

Clin Experimental Allergy

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318

241

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The Th2 cytokines interleukin 4 (IL‐4) and IL‐13 and the heterodimeric IL‐4 receptor (IL‐4R) complexes that they interact with play a key role in the pathogenesis of allergic disorders. Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL‐4 receptor alpha chain (IL‐4Rα), common to both IL‐4R complexes: type 1 (IL‐4Rα/γc; IL‐4 specific) and type 2 (IL‐4Rα/IL‐13Rα1; IL‐4 and IL‐13 specific). In this review, we detail the current state of knowledge of the different signalling pathways coupled to the IL‐4R complexes and examine the possible mechanisms of Dupilumab action and survey its clinical efficacy in different allergic disorders. The development of Dupilumab and the widening spectrum of its clinical applications is relevant to the current emphasis on precision medicine approaches to the blockade of pathways involved in allergic diseases.

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Section: Il‐4r Signalling In Tolerance Modulationmentioning

confidence: 99%

Section: Dupilumab For Food Allergymentioning

confidence: 99%

Mechanisms of Dupilumab

Harb

Chatila

2019

Clin Experimental Allergy

Self Cite

318

241

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“…As there is limited data on the sustainability of desensitization of multifood-OIT [ 23 , 24 ], Andorf et al conducted a multisite multifood-OIT study to compare the efficacy of successful desensitization with sustained dosing vs discontinued dosing after multifood-OIT [ 25 ]. Results suggested that sustained desensitization after multi-OIT best occurs through continued maintenance OIT dosing of either 300 mg or 1 g of each food allergen as opposed to discontinuation of multi-OIT.…”

Section: Oral Immunotherapymentioning

confidence: 99%

Therapeutic perspectives in food allergy

et al. 2020

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Background: In the last twenty years, several studies have been conducted in the search for new therapeutic strategies in patients with food allergy; in particular, after the failure of injection immunotherapy, three different routes of administration, oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT), have been tested. The aim of this manuscript is to review OIT, SLIT, and EPIT clinical trials on food allergies and to suggest advantages and limits of the different routes of immunotherapy administration. Main body: Of the three different routes of immunotherapy used in the treatment of food allergy, OIT is, at present, the only one actually able to induce an increase in tolerance in the majority of patients. However, its use is affected by serious secondary effects, such as major abdominal symptoms and anaphylaxis. The combination with omalizumab reduces the percentage of serious side effects. There are not many studies with SLIT for food allergy, but they have nevertheless shown that it is possible to obtain an increase in tolerance; however, this increase is modest in comparison with that obtained by OIT. EPIT, performed through the diffusion of allergens on intact skin, is the most recent form of immunotherapy. Although there are many works on EPIT carried out in laboratory animals, only few clinical studies have been published in humans. EPIT, unlike OIT and SLIT, is not responsible for systemic secondary effects such as anaphylaxis and eosinophilic oesophagitis but only for local and mild effects in areas where the devices are applied. Moreover, EPIT is characterized by high patient adherence. Conclusion: OIT seems to have a prevalent application in patients who do not report previous symptoms of systemic or gastroenteric anaphylaxis, while SLIT and EPIT, in particular, could be more preferentially used in patients with a risk of anaphylaxis.

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“…With regard to the mechanism of action, in oral immunotherapy for food allergy (which, although not accepted in guidelines, has been used by some authors for desensitization to food allergy), one study demonstrated that supplementing treatment with omalizumab resulted in specific desensitization to the administered food, with an initial omalizumab-dependent depletion of allergen-reactive T cells and subsequent increase in allergen-specific T-regulatory cells that induced the reversal of Th2 cell-like activity. 69 It is unlikely that this mechanism of action is limited to food-allergy immunotherapy supplemented with omalizumab, and may also work in other forms of immunotherapy in combination with omalizumab.…”

Section: Issues To Be Investigated In Omalizumab Treatmentmentioning

confidence: 99%

Two decades with omalizumab: what we still have to learn

Incorvaia

Mauro

Makrì³

et al. 2018

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From its availability for clinical use nearly two decades ago for severe asthma, omalizumab has gained strong evidence of efficacy and safety in the treatment of severe asthma not controlled by standard-of-care therapy. It has been acknowledged by Global Initiative on Asthma guidelines as add-on therapy against severe uncontrolled asthma. Thanks to controlled trials supporting its efficacy, omalizumab has also been licensed for the treatment of chronic spontaneous urticaria. The optimal duration of treatment in either disease has not been established. Despite its high price, omalizumab appears to be cost-effective in severe uncontrolled asthma as well as in chronic urticaria. The literature suggests a wide range of applications for omalizumab in various disorders regardless of allergic or non-allergic pathophysiology.

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Oral immunotherapy with omalizumab reverses the Th2 cell‐like programme of regulatory T cells and restores their function

Cited by 64 publications

References 40 publications

Mechanisms of Dupilumab

Mechanisms of Dupilumab

Therapeutic perspectives in food allergy

Two decades with omalizumab: what we still have to learn

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