IgE antibodies, FcεRIα, and IgE-mediated local anaphylaxis can limit snake venom toxicity.

BACKGROUND: Type 2 cytokine-related immune responses associated with development of antigen-specific IgE antibodies can contribute to pathology in patients with allergic diseases and to fatal anaphylaxis. However, recent findings in mice indicate that IgE also can enhance defense against honeybee venom. OBJECTIVE: We tested whether IgE antibodies, IgE-dependent effector mechanisms, and a local anaphylactic reaction to an unrelated antigen can enhance defense against Russell viper venom (RVV) and determined whether such responses can be influenced by immunization protocol or mouse strain. METHODS: We compared the resistance of RVV-immunized wild-type, IgE-deficient, and Fcer1a-deficient mice after injection of a potentially lethal dose of RVV. RESULTS: A single prior exposure to RVV enhanced the ability of wild-type mice, but not mice lacking IgE or functional FcεRI, to survive challenge with a potentially lethal amount of RVV. Moreover, IgE-dependent local passive cutaneous anaphylaxis in response to challenge with an antigen not naturally present in RVV significantly enhanced resistance to the venom. Finally, we observed different effects on resistance to RVV or honeybee venom in BALB/c versus C57BL/6 mice that had received a second exposure to that venom before challenge with a high dose of that venom. CONCLUSION: These observations illustrate the potential benefit of IgE-dependent effector mechanisms in acquired host defense against venoms. The extent to which type 2 immune responses against venoms can decrease pathology associated with envenomation seems to be influenced by the type of venom, the frequency of venom exposure, and the genetic background of the host.

The economic burden of asthma prior to death: a nationwide descriptive study.

Background: In addition to the clinical burden, asthma is responsible for a high economic burden. However, little is known about the economic burden of asthma prior to death. Objective: We performed an economic analysis to describe the costs during 12 and 24 months prior to asthma death between 2013 and 2017 in France. Methods: An observational cohort study was established using the French national health insurance database. Direct medical and non-medical costs, as well as costs related to absence from the workplace, were included in the analysis. Results: In total, 3,829 patients were included in the final analysis. Over 24 and 12 months prior to death, total medical costs per patient were €27,542 [26,545-28,641] and €16,815 [16,164-17,545], respectively. Total medical costs clearly increased over 24 months prior to death. Over 12 months prior to death, costs increased significantly according to age categories, with mean total costs of €8,592, €15,038, and €17,845, respectively, for the categories <18 years old, 18-75 years old, and 75+ years old (p < 0.0001). Over 12 months prior to death, costs were statistically higher in patients with a dispensation of six or more SABA canisters compared to those with a dispensation of five or less canisters (p < 0.0001). In multivariate analysis, comorbidities, hospital as location of death, and dispensation of 12 or more canisters of SABA per year are independent factors of the highest costs. Conclusion: To conclude, the economic burden of asthma death is high and increases with time, age, and SABA dispensation.

Combining Anti-IgE Monoclonal Antibodies and Oral Immunotherapy for the Treatment of Food Allergy.

Immunoglobulin E (IgE)-mediated food allergy is a real public health problem worldwide. The prevalence of food allergy is particularly high in children. Patients with food allergy experience high morbidity with a change in quality of life due to the risk of severe anaphylaxis. Current treatment options are poor. Allergen avoidance is widely recommended but exposes patients to accidental ingestion. Oral immunotherapy is also used in patients with food allergies to the most common allergens. Oral immunotherapy consists of a daily administration of small, gradually increasing amounts of allergens to induce desensitisation. This procedure aims at inducing immune tolerance to the ingested food allergens. However, some patients experience adverse reactions and discontinue oral immunotherapy.Given that IgE plays a crucial role in food allergy and anti-IgE are effective in allergic asthma, the use of anti-IgE therapeutic monoclonal antibodies (mAbs) such as omalizumab has been assessed in food allergy patients. The use of omalizumab as a monotherapy in food allergy has not been extensively studied but looks promising. There is more published evidence regarding the effect of omalizumab and oral immunotherapy in food allergy. Given the promising results of oral immunotherapy regarding sustained tolerance in clinical trials and the potential capacity of omalizumab to reduce symptoms in case of accidental exposure, a strategy combining oral immunotherapy with omalizumab pre-treatment has been suggested as a safer option in patients with severe food allergy compared to isolated therapy. Omalizumab seems useful in ensuring safer administration of oral immunotherapy with the oral immunotherapy maintenance dose being reached more rapidly. Quality-of-life improvement is greater with oral immunotherapy + omalizumab compared to oral immunotherapy alone. Moreover, sustained unresponsiveness is achieved more frequently with omalizumab. Considering that precision medicine and personalised therapy are major goals for allergic diseases, predictive biomarkers are crucial in order to identify food allergy patients more likely to benefit from anti-IgE therapies.