Asthma and Allergy: The Role of Inflammation

Nearly 8% of children under the age of three and 4% of adults suffer from food allergies, which cause not only unpleasant symptoms such as dermatitis and diarrhea, but can cause fatal anaphylactic shock. Allergic reactions occur when food ingredients, such as eggs, shellfish, or peanut proteins, stimulate white blood cells called mast cells, and excessive amounts of histamine or cytokines enter the bloodstream, resulting in inflammation of the skin, eyes, or gastrointestinal tract.
In 2012, researchers reported that a small protein called histamine-releasing factor (HRF) plays a pro- inflammatory role in asthma. The work continued this year, and it turned out that this protein also serves as an “amplifier” of food allergies. A new biochemical mechanism is reported to regulate this factor, paving the way for the development of blood tests that can help predict which patients will respond to allergy therapy , supporting the idea that drugs designed to block said protein could prevent food allergies .
Allergens increase levels of antibodies called immunoglobulin E (or IgE ), which then bind to mast cells, and when the allergen hits IgE , histamine is released, according to the authors of the study. Early in the study, scientists suspected that allergens were often present at very low levels, perhaps too low to activate mast cells in this way. Recent evidence has confirmed that after triggering allergens, histamine-releasing factor binds to IgE and then activates mast cells, increasing inflammation.
To test the theory, the team raised mice sensitive to egg white and treated them with an oral histamine-releasing protein inhibitor developed by the lab for use in asthma-related experiments. To test the effectiveness of the inhibitor, the scientists re-exposed treated and untreated mice to the allergen. As expected, the untreated mice developed diarrhea and signs of intestinal inflammation. However, these symptoms were delayed or significantly less pronounced in mice treated with an inhibitor that reduced the reactivity of mast cell allergens isolated from the intestines of allergic mice. to treat people with food allergies, the authors say. The team observed higher levels of IgE antibodies highly sensitive to HRF in the blood of egg-allergic children, indicating that HRF contributes to food allergies in humans, as it does in mice.
The group then followed the same children after starting an anti-allergic treatment called oral allergy immunotherapy, in which patients consume increasing amounts of eggs several times a day for several weeks. Once patients achieve desensitization, they continue to consume eggs for twelve months. Egg products are then withdrawn from the diet for two weeks before repeated exposure to egg protein, as a test of the strength of the therapy. two weeks after cessation of therapy, a low level of IgF- reactive IgE in the blood after therapy was maintained. In contrast, children who showed re-sensitization to egg whites immediately after interruption of therapy showed an increase in IgF- reactive IgE .
The experiment showed that HRF is a potential target for drugs that are effective in animal models. If a patient’s allergy goes unchecked regardless of HRF levels, this could mean that the condition would be more difficult to treat, the authors say. These tests also warrant future clinical monitoring of HRF-resistant
IgE levels as a predictor of oral allergy immunotherapy outcomes. The lab remains focused on developing potent HRF inhibitors and is currently testing them using the mouse models described in the study. The goal of scientists is to reduce the risk of developing allergic shock in patients. In the future, such people may take an oral inhibitor as a preventive measure.

event_note March 26, 2022

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