The human being has at his service the most loyal and efficient defensive army: the immune system, an intricate network of cells, tissues and organs that tirelessly protect the body from external threats. And although they are good at what they do, mercilessly detecting and annihilating harmful elements, they are not indefectible. Sometimes, they fail. For example, identifying as an enemy something that is not, such as a peanut or the pollen of a flower. When this happens, allergies arise, which are nothing more than an abnormal reaction of the immune system to a non-harmful substance. The scientific community has thoroughly studied this defensive failure, but there are unresolved knowledge gaps, such as why some allergies persist over time. Two studies published this Wednesday in Science Translational Medicine delve into this mystery and suggest that a type of immune cells are responsible for this memory because they function as reservoirs of antibodies that cause the body’s exaggerated response to some allergens.
Allergies are, in the words of Joan Bartra, head of the Allergology service at the Hospital Clínic of Barcelona, “a defect of the immune system. Within an allergic response there are different mechanisms. But the most common of all is hypersensitivity allergy, which is mediated by IgE antibodies: cells, B lymphocytes, produce immunoglobulins E (IgE) against something external, that is, the allergen. In this way, when the allergen is in contact with the body, we have these defenses prepared, the IgE, which activate the cells responsible for the allergic reaction,” explains the allergist. In practice, this activation of the immune system translates into heterogeneous symptoms of varying severity, which can range from mild urticaria to anaphylaxis, which is a potentially fatal systemic allergic reaction. 10% of the world’s population suffers from some allergy to environmental elements or foods, highlight the authors of one of the studies.
The great mystery that has loomed over allergists for years is why some allergies resolve spontaneously and others persist. “What we know is that IgE is produced from an immunological dialogue between different cells: the B lymphocytes give the response to manufacture IgE and tell the plasmacytes [un tipo de linfocitos B] They manufacture them in large quantities, but these cells are not eternal, they have limited memory. So, if the large amount of IgE is manufactured by plasma cells, but it is known that these have a limited life, why in the vast majority of IgE-mediated allergies, even if the allergen is not present, do they perpetuate over time? ?”, explains Bartra.
Two research groups propose, in separate articles published simultaneously in Science Translational Medicine, a common explanation: both describe a population of immune system cells, specifically, a group of memory B cells, as potentially responsible for that allergic memory. “We know that allergen-specific IgE has a short half-life in humans, around 48 hours. Furthermore, it was previously thought that persistently high levels of IgE were due to the long-lived cells that produce this immunoglobulin, plasma cells. This is not the case, as we now know that these IgE-producing plasma cells are actually short-lived. “This suggests that the IgE reservoir, in other words, the ability to regenerate IgE after new exposure to allergens, resides in other cells, which we now know are memory B cells,” the co-author of one explains by email. of the studies, Manel Jordana, a Catalan allergist who has lived in Canada for more than 40 years and is a researcher at MacMaster University.
A group of American researchers have discovered, when studying a pediatric population with peanut allergy, that the presence of this type of immune cells was correlated with IgE concentrations and they propose that these memory B cells “are involved in the persistence of the Food Allergy”. Along the same lines, Canadian researchers, including Jordana, conclude, after analyzing samples from patients with different allergies and healthy participants, that this population of immune cells “is a reservoir of memory IgE.” “In this paper we report the discovery of a certain type of allergen-specific memory B cell (MBC2), which is destined to become an IgE-producing plasma cell upon re-exposure to the allergen. The existence of these cells may explain the lifelong nature of some food allergies. This is interesting because it indicates that these cells may be a marker for the development of clinical allergy; In other words, it may indicate a predisposition to develop clinical allergy,” Jordana specifies.
Therapeutic objective
The scientist clarifies that the two articles “are not identical, but complementary,” which provides, he says, “greater solidity to the discovery because it shows that two independent groups made the same central observation.” Jordana assures that his findings turn these cells “into a new therapeutic target.” “That is, killing these cells or disabling their ability to become IgE-producing plasma cells can have a very significant impact for patients with food allergies.”
The findings suggest a path towards new therapeutic targets, even with drugs that are already currently used (for example, dupilumab, used for atopic dermatitis) and that could potentially reduce the populations of these cells. “The discovery of MBC2 paves a clear path for future research, as many questions remain to be answered. For example, we are working intensively on the identification of the cellular and molecular signals involved in the activation of MBC2 and their transition to IgE-producing cells after re-exposure to the allergen. Likewise, we are working very actively to elucidate whether MBC2 can be reprogrammed, that is, if they can become a cell that, instead of IgE, produces harmless antibodies,” Jordana questions.
For Victoria Cardona, head of the Allergology service at the Vall d’Hebron Hospital in Barcelona, these investigations “are not crucial, but they are important: It is an important piece of the puzzle because it is still surprising to maintain the immune response over time,” agrees the doctor, who has not participated in the studies. For his part, Ignacio Dávila, president of the Spanish Society of Allergology and also not involved in these investigations, points out that the studies are of good quality and points out their potential: “Finding these cells can help manage IgE memory and, potentially, in the future, to modify it.” Bartra also celebrates the findings and highlights their clinical impact: “It has clinical connotations to explain why immunotherapy [para la alergia] is effective in the short term and why a person might have a return allergy after months of tolerance to the allergen. Now we have something, an objective, to be able to modulate the response as science advances. These studies make you question dogmas and propose strategies for what we do now and why we don’t always find answers for the patient.”