A specific type of immune system cells are responsible for allergies lasting for years and, in many cases, lasting a lifetime. This is the conclusion reached by two independent studies published simultaneously this Wednesday in the journal Science Translational Medicine, after analyzing in detail the immune cells of children and adults allergic to peanuts, pollen and mites. The advance opens the door to developing new therapies against allergies.
“The articles are not identical, but complementary,” Manel Jordana, an immunologist at McMaster University in Hamilton, Canada, told La Vanguardia. The expert of Catalan origin, who has participated in one of the studies, considers that the simultaneous publication of the finding “gives greater strength to the discovery, because it demonstrates that two independent groups made the same central observation. This, in science, is a very important validation.”
The presence of these cells in a person's blood "can be considered a risk factor for developing allergic diseases, and their numbers can be analyzed as a parameter of the progression or resolution of the disease," he explains in an email to this Maria Curotto de Lafaille, researcher at the Mount Sinai School of Medicine, in the United States, who coordinated the second work.
Both experts highlight that the advance opens the door to investigating new therapeutic options to treat allergic conditions, which focus on addressing and limiting the activity of this specific set of cells. The possibility of a new treatment is key for a group of diseases on the rise in the global context, especially in the West. More than 10% of the world's population suffers from an allergy today, and the figure is expected to reach 50% by 2050, according to estimates by the World Health Organization.
Allergies are an exaggerated response of our immune system to a substance that is not harmful to most people. When this substance, the allergen, enters the body of the allergic person, the immune system activates plasma cells, white blood cells whose function is to produce antibodies that fight the threat - although, in this case, such threat is non-existent. This overly intense defense is what causes the allergic reaction.
Most allergies last a long time and can last a lifetime, something that does not fit with the relatively short survival of both IgE antibodies—the specific type of defense that is activated in allergies—and cells. plasmatic. If the agents that mediate the allergic response disappear from our body after a short time, how can the condition last for years?
Both investigations have resolved this apparent paradox by finding a specific type of cells specialized in detecting allergens, called type 2 polarized memory B cells. “They are cells that 'maintain the memory' of IgE immune responses,” summarizes Curotto. When a person who has not suffered an allergic reaction for a long time is exposed to an allergen again, they recognize the substance, transform into plasma cells and produce IgE antibodies that, again, trigger an allergic reaction.
The Mount Sinai team analyzed 58 children with peanut allergies and 13 healthy children. The former showed greater amounts of these memory cells in their blood compared to the latter. The difference in quantity was also noticeable when comparing the most allergic individuals with the least—the former also had a higher concentration.
Furthermore, they observed that the surface of the cells of the most allergic individuals was full of proteins capable of recognizing, with great precision, a specific compound in peanuts, which makes them capable of responding to the supposed threat. Curotto argues that the presence of these very precise receptors is probably a common feature of these cells also with other allergens such as pollen or mites.
In fact, the second of the investigations, in which Jordana participated, analyzed six adults allergic to birch pollen, four others allergic to mites and five healthy people. They studied more than 90,000 cells from these 15 individuals and, again, found memory cells with characteristics similar to those of Curotto, capable of producing IgE antibodies against allergens.
To validate the relationship between these cells and allergic reactions, in this case the scientists studied the antibodies generated by the patients after the first month of treatment with immunotherapy, the only therapeutic option against allergies that exists today. It consists of exposing the patient to the allergen in very small doses, so that the body stops recognizing it as dangerous after years.
However, during the first month, the therapy triggers the production of IgE antibodies. Jordana's team took advantage of this to analyze the relationship of the antibodies and thus identify their origin. They saw that the IgEs were closely related to the memory cells they had identified, revealing that they had been produced by them.
The similar results achieved following different study methodologies give solidity to a finding that promises to revolutionize the treatment of allergies, but still leaves many questions unanswered. No team has been able to describe how these memory cells are activated to begin producing antibodies, or why some allergies last longer over time than others.
“We are working very actively to elucidate whether these cells can be reprogrammed, that is, if they can become cells that, instead of IgE, produce harmless antibodies,” describes Jordana. The next steps for both groups will focus on clarifying these mechanisms of action, to definitively open the door to new allergy treatments.
