Two studies have identified elusive immune cells that sustain allergies over the long term, frequently for a lifetime, raising the possibility that allergy sufferers may one day be able to eliminate the cause of their congestion, itchy skin, swollen lips, and throat.
Two separate teams of researchers report February 7 in Science Translational Medicine that type 2 memory B cells, or MBC2s, are a specific subset of immune cells that carry the memory of proteins that trigger allergies. Although this subgroup of memory B cells is ready to produce the kind of antibodies that cause allergies, memory B cells are essential for providing long-lasting defense against infectious illnesses.
Finding the identify of the cells could reveal new avenues for the diagnosis, treatment, or even cure of allergies.
Around 25% of children and 1/3 of adults in the US suffer from allergies, which can cause everything from minor seasonal sniffles to potentially fatal reactions to certain foods or insect stings. When the immune system attacks harmless proteins with an antibody known as IgE, allergies result. These antibodies are normally only used to combat parasitic worms, but in allergic individuals, they also target innocent substances like pollen, peanuts, and pet dander (SN: 11/4/22).
Some allergies are permanent, while others go away with time or with treatment. Researchers have been looking for the cause of persistent allergies for many years.
Researchers have recently discovered that immune system memory cells related to immunizations and natural illnesses may be implicated. These memory B cells generate IgG antibodies, which are a distinct type of antibodies that neutralize toxins and protect against bacterial and viral illnesses. However, no one knew precisely which of those cells was remembering allergens, or how they changed to produce the IgE antibodies that cause allergies.
Two research teams thoroughly examined the immune cells of both individuals with allergies and those without in order to identify the strange cells.
More than 90,000 memory B cells from six individuals with birch allergies, four individuals allergic to dust mites, and five individuals without allergies were analyzed by immunologist Joshua Koenig and associates. The researchers discovered specific memory B cells, which it designated MBC2s, that create antibodies and proteins linked to the immune response that fights parasitic worms and causes allergies. They did this by using a technique called RNA sequencing to determine what individual cells were generating.
In a different study, Koenig and associates went fishing for memory B cells from individuals with peanut allergies using a peanut protein. Researchers extracted the same kind of cells that are present in individuals allergic to dust mites and birch trees. When patients with peanut allergies began receiving treatment to desensitize them to peanut allergens, those cells multiplied and formed IgE antibodies, which cause allergies (SN: 9/4/19).
According to Koenig of McMaster University in Hamilton, Canada, “that’s a smoking gun observation.” “You find that allergic individuals have these cells. These cells are responsible for producing these antibodies, which is how this memory is maintained, and it is absent in nonallergic individuals.
Similar cells, dubbed type 2 memory B cells by Maria Curotto de Lafaille, an immunologist at the Icahn School of Medicine at Mount Sinai in New York City, were also shown to be more prevalent in 58 children who were allergic to peanuts than in 13 children who were not.
According to Cecilia Berin, an immunologist and allergist at Northwestern University Feinberg School of Medicine in Chicago, it is evident that both groups have discovered the same cells. “Very consistent findings between the two groups,” according to her research.
The cells are ready to change from producing protective IgG antibodies to IgE antibodies that cause allergies, according to research by Lafaille’s group. The cells were producing the RNA for IgE even prior to the switch, but they were not producing the protein. The cells can change the sort of antibodies they produce in response to the allergen by producing that RNA. She claims that “they are one step ahead of other cells to respond and to switch.”
Her research found that the signal to switch is partially dependent on a protein called JAK. According to Lafaille, blocking JAK from delivering the signal may help keep memory cells from flipping to producing IgE. A medication called abrocitinib, a JAK inhibitor, is being tested on individuals with food allergies by other Mount Sinai researchers.
Additionally, according to Lafaille, allergists might be able to look at certain features of these memory cells to anticipate if a patient’s allergy will persist over time or go away with therapy.
Scientists may someday be able to find more strategies to starve or destroy the allergy cells if they know which population of cells stores allergies in long-term memory, according to Berin. “It’s possible that you could eliminate not just your allergy to peanuts but all of your allergies.”
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