The Secret Behind Springtime Sniffles

New insight into the molecular mechanisms behind allergic reactions has been unveiled, which leads us a step closer to banishing the infamous seasonal congestion.

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By Winnie Yang

As spring creeps into the air, an all-too-familiar, anxiety-inducing sniffle can be heard on subway platforms, hallways, and even in your home—seasonal allergies. Even if you don’t have allergies, you probably know someone who does. In fact, a study conducted by the National Health Center for Health Statistics in 2021 estimates that one-third of American adults are diagnosed with an allergic condition, with symptoms ranging from mild irritation to serious convulsions. Its widespread prevalence and range of symptoms have hindered experts in their search for successful, long-term treatment. If researchers hope to develop an efficient solution, they must first understand how allergies function at a molecular level.

Allergic reactions occur when the immune system unleashes an antibody called allergen-specific immunoglobulin E (IgE) on harmless proteins that the body falsely perceives as dangerous. Then, IgEs bind to white blood cells called basophils and a type of tissue cell called mast cells. As a programmed defense mechanism, the cells secrete an irritant called histamine, which causes inflammation in the surrounding environment. The severity of the symptoms is partially decided by the type of histamine receptors, the specialized molecules that activate cell responses, which receive the irritant. If histamine binds to H1 receptors, found throughout the body, itchy skin, an increased heart rate, and nasal congestion can occur. However, if histamine is received by H2 receptors, which are usually located in the stomach, lower blood pressure and anaphylaxis—the constriction of airways—may occur. This range of symptoms, which varies by individual, has made it difficult to develop a general solution to allergies. 

However, McMaster University scientists have recently discovered the exact cell that initiates an allergic reaction. Using tetramers—fluorescent molecules containing allergens—they were able to locate white blood cells called memory B cells. Experts have long known that memory B cells help activate an immune response to protect against viral infections, so these scientists investigated how the intracellular processes of memory B cells interacted with allergic reactions. They gathered over 90,000 memory B cells from six people with birch allergies, four people with dust mite allergies, and five people with no allergies. Then, researchers identified which proteins each memory B cell makes and looked for any abnormal protein amounts between participants with and without allergies. Researchers found high amounts of Type 2 memory B cells (MBC2s) amongst people with allergies, whereas non-allergic people had very few, if any, present in their samples. This led them to the conclusion that MBC2s were heavily implicated in the production of inflammatory IgEs in response to the allergens and could potentially cause allergic reactions. 

On the same day as the study from McMaster University, Icahn School of Medicine at Mount Sinai scientists published another study that supported findings the McMaster University scientists discovered. They sampled the blood of 58 children allergic to peanuts, and 13 children without allergies and found that a special type of cell was significantly more abundant in the allergic group––the same MBC2s that the scientists from McMaster University isolated.

 By studying the pediatric blood samples, the Mount Sinai researchers also supported earlier hypotheses on how memory B cells actually cause allergies. In one study, the researchers replicated mass amounts of IgEs from patients with allergic asthma and atopic dermatitis, which are conditions known to produce abnormally high levels of IgEs. In a trial where all the IgEs were removed, more would suddenly appear. This led scientists to hypothesize that there was a pre-existing mechanism that produced IgEs in people with allergies. After examining the genetic coding, DNA, for the memory B cells, they found that memory cells produce two types of antibodies, protective Immunoglobulin G (IgGs) and IgEs. Usually, the memory B cells receive the genetic code for both of those antibodies but don't actually produce IgEs. However, when mediators of intercellular communication called Janus Kinase (JAK) proteins bind to memory B cells’ membrane receptors, they switch to creating IgEs. This means IgE production ultimately relies on JAK signals.

A clearer understanding of the mechanisms of allergic reactions can lead to the development of more advanced treatments. Common store-bought allergy treatments are simply antihistamines, which only temporarily block histamine to mediate mild symptoms. Usually, further notable allergy treatments just respond to the production of IgEs. For example, Xolair, which is used to treat allergic asthma, stops IgEs from binding to mast cells and basophils at the site of histamine release. In contrast, the Mount Sinai researchers theorize that using an inhibitor to block JAK signals could effectively stop the transition of IgG antibodies to IgEs. In tandem, the production of IgEs would stop, leading to a lower risk of reactionary symptoms as allergic reactions are inhibited at their root cause. However, further experimentation is still needed to expose the full molecular chain reaction and develop realistic immunotherapy drugs. 

Allergies are extremely common worldwide but have no definitive cure due to their wide range of symptoms. Nevertheless, the new research from the McMaster and Mount Sinai scientists open doors to a new approach to attacking allergy-causing cells. Though the task of translating this information into an allergy-curing drug is extremely daunting, these researchers have successfully provided us with a clearer target. With more research, that dreaded sniffle might fade into nothing but a memory and leave your mind and nose at peace.