Emerging Therapies for Eosinophilic Gastrointestinal Diseases

Peterson, Kathryn A.; Safroneeva, Ekaterina; Schoepfer, Alain

doi:10.1016/j.jaip.2021.07.031

Cited by 17 publications

(11 citation statements)

References 43 publications

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“…For example, dupilumab, an anti‐interleukin 4 (IL4) receptor alpha monoclonal antibody, has already been approved for the treatment of atopic dermatitis and allergic asthma, while mepolizumab, an anti‐IL5 monoclonal antibody, has already been approved for allergic asthma 78 ,. 79 Moreover, lirentelimab, a monoclonal antibody targeting an inhibitory receptor Siglec‐8, could represent an interesting therapeutical agent targeting both the allergic disorders and EGID, since this receptor is present only on mastcells, basophils, and eosinophils, all key players in both disease groups 18,80,81 . The main molecular targets of monoclonal antibodies are shown in Figure 1.…”

Section: Discussionmentioning

confidence: 99%

“… 78 , 79 Moreover, lirentelimab, a monoclonal antibody targeting an inhibitory receptor Siglec‐8, could represent an interesting therapeutical agent targeting both the allergic disorders and EGID, since this receptor is present only on mastcells, basophils, and eosinophils, all key players in both disease groups. 18 , 80 , 81 The main molecular targets of monoclonal antibodies are shown in Figure 1 .…”

Section: Discussionmentioning

confidence: 99%

“… 16 However, a comprehensive view of their pathogenesis is still lacking, and this contributes, along with other factors, to the substantial diagnostic delay and therapeutic uncertainty 17 ,. 18 Moreover, the association with allergic disorders must be considered when managing patients with EGID, as they may share a common etio‐pathological background and hence some clinical features 2,9,17 . In fact, some patterns of disease association are common in these patients, such as the co‐occurrence of allergic asthma, rhinitis, and esophageal symptoms, or the occurrence of gastrointestinal symptoms in patients receiving oral immunotherapy for food allergy, or else the occurrence of isolated diarrhea in atopic patients 6,19,20 .…”

Section: Introductionmentioning

confidence: 99%

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Primary eosinophilic gastrointestinal disorders and allergy: Clinical and therapeutic implications

Rossi

Lenti

Merli

et al. 2022

Clinical & Translational All

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Primary eosinophilic gastrointestinal disorders (EGID) are increasingly prevalent, immune‐mediated, chronic conditions which primarily affect pediatric and young adult patients, leading to substantial disease burden, and poor quality of life. EGID may either involve single portions of the gastrointestinal tract (i.e., esophagus, stomach, small bowel, and colon) or a combination. Their strong association with allergic disorders has been recently recognized, and although their shared pathophysiological basis remains partly elusive, this feature greatly impacts the diagnostic and treatment work‐up. We herein critically discuss the current knowledge on the association of EGID and allergic disorders, including atopic dermatitis, allergic rhinitis, allergic asthma, and food or drug allergy. In particular, we reviewed the literature focusing on their epidemiology, pathophysiological basis and mechanisms, and diagnostic strategies. Finally, we discuss the currently ongoing clinical trials targeting EGID and allergic diseases, including, among others the monoclonal antibodies dupilumab, mepolizumab, benralizumab, and lirentelimab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Primary eosinophilic gastrointestinal disorders and allergy: Clinical and therapeutic implications

Rossi

Lenti

Merli

et al. 2022

Clinical & Translational All

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“…Generally, patients affected by EGE show excess eosinophils in the GI tract and high levels of IgE, suggesting the presence of an allergic component and an implication of a mechanism involving Th2, even if the origination and the development of this disease is not well understood [30][31][32]. Eosinophilic esophagitis is the most studied type of EGID with a standardized diagnosis and therapy, whereas the data on the other types of EGIDs are limited even if eosinophilic gastritis, gastroenteritis, and colitis are increasing in their prevalence in the last decade, making further research necessary [33]. Acute caffeine treatment in our study triggered eosinophilic infiltration in the rats comparable to that one observed in EGE, making this treatment a good model to study acute eosinophilia, and laying the foundation for further studies necessary to highlight the origin and development of chronic eosinophilic infiltration typical of EGIDs.…”

Section: Discussionmentioning

confidence: 99%

Effects of Energy Drink Acute Assumption in Gastrointestinal Tract of Rats

et al. 2022

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Energy drinks (EDs) are non-alcoholic beverages containing high amounts of caffeine and other psychoactive substances. EDs also contain herbal extract whose concentration is usually unknown. EDs can have several adverse effects on different organs and systems, but their effects on the gastrointestinal (GI) tract have been poorly investigated. To determine the acute effects of EDs on the GI tract, we administered EDs, coffee, soda cola, or water to Sprague–Dawley rats (n = 7 per group, randomly assigned) for up to five days, and analyzed the histopathological changes in the GI tract. Data were compared among groups by Kruskal–Wallis or Mann–Whitney tests. We found that, while EDs did not cause any evident acute lesion to the GI tract, they triggered eosinophilic infiltration in the intestinal mucosa; treatment with caffeine alone at the same doses found in EDs leads to the same effects, suggesting that it is caffeine and not other substances present in the EDs that causes this infiltration. The interruption of caffeine administration leads to the complete resolution of eosinophilic infiltration. As no systemic changes in pro-inflammatory or immunomodulating molecules were observed, our data suggest that caffeine present in ED can cause a local, transient inflammatory status that recruits eosinophils.

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“…No therapy for the management of EGIDs is currently approved by the U.S. Food and Drug Administration (FDA). Major treatment strategies for EGIDs, including diet therapy, steroid therapy, anti-IL-5 treatment, and anti-IL-13 treatment, lack efficacy, indicating that the pathogenesis of EGIDs requires further exploration ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

OX40 Expression in Eosinophils Aggravates OVA-Induced Eosinophilic Gastroenteritis

Tian

Zhou

et al. 2022

Front. Immunol.

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Background & AimsEosinophils are the main inflammatory effector cells that damage gastrointestinal tissue in eosinophilic gastrointestinal diseases (EGIDs). Activation of the OX40 pathway aggravates allergic diseases, such as asthma, but it is not clear whether OX40 is expressed in eosinophils to regulate inflammation in EGIDs. In this study, we assessed the expression and effect of OX40 on eosinophils in WT and Ox40-/- eosinophilic gastroenteritis (EGE) mice.MethodsEosinophil infiltration, ovalbumin (OVA)-specific Ig production, OX40 expression and inflammatory factor levels in the intestine and bone marrow (BM) were investigated to evaluate inflammation.ResultsWe confirmed that OVA-challenged mice produced high levels of Ox40, Mbp, Ccl11, Il5, Il4, Il13, and Il6 mRNA and a low level of Ifng mRNA in the intestine. Increased eosinophils were observed in intestinal and lymph tissues, accompanied by significantly upregulated OX40 and Type 2 cytokine production in eosinophils of EGE mice. Ox40 deficiency ameliorated OVA-induced inflammation, eosinophil infiltration, and cytokine production in the intestine. Consistently, Ox40-/- eosinophils exhibited decreased proliferation and proinflammatory function. The stimulation of the agonistic anti-OX40 antibody, OX86, promoted the effect of OX40 on eosinophils. The present study also showed that Ox40 deficiency dampened the Traf2/6-related NF-κB signaling pathway in eosinophils.ConclusionsOX40 may play a critical role in the progress of OVA-induced EGE by promoting the maturation and function of eosinophils via the Traf2/6-related NF-κB signaling pathway.

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Emerging Therapies for Eosinophilic Gastrointestinal Diseases

Cited by 17 publications

References 43 publications

Primary eosinophilic gastrointestinal disorders and allergy: Clinical and therapeutic implications

Primary eosinophilic gastrointestinal disorders and allergy: Clinical and therapeutic implications

Effects of Energy Drink Acute Assumption in Gastrointestinal Tract of Rats

OX40 Expression in Eosinophils Aggravates OVA-Induced Eosinophilic Gastroenteritis

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