Severe Allergies to Bee Stings may be Malfunctioning Evolutionary Response

New research from Stanford University School of Medicine suggests there may be an evolutionary explanation for severe allergic reactions to bee stings, providing the first evidence that the same immune response triggered by allergies may have evolved to serve a protective role against toxins.

Severe allergic reactions, the researchers suggest, could be an evolutionary defense mechanism gone haywire.

Innate immune system response occurs when a foreign substance such as a pathogen or toxin is introduced to the body for the first time.

Previous studies have shown that immune cells called mast cells, which reside in most body tissue, produce enzymes that detoxify components of snake venom and that mast cells also enhance innate resistance to honey bee venom.

The new research focused on a type of antibody known as IgE, which binds to the surfaces of mast cells during an allergic reaction. Most of what is understood about IgE antibodies is within the context of allergies, the researchers said.

"It was kind of a dogma that most IgE-related responses are detrimental," said Philipp Starkl, one of the study's lead authors. "We and others speculated that there should be some very positive evolutionary pressure to keep these cells and these antibodies, because if they were just bad and deleterious, they would have been eliminated."

Revisiting a largely ignored theory proposed by Margie Profet in 1991, Starkl and his colleagues hypothesized that "IgE might be required for protection against a lethal sting, and that allergies are an extreme, and maladaptive, example of this type of defense."

The researchers used mice to test their hypothesis, first injecting the rodents with a low dose of venom equivalent to one or two stings. Those mice developed more venom-specific immune cells and higher levels of IgE antibodies than a control group.

After three weeks, the test group and control group were both injected with a potentially lethal dose of bee venom. The mice that has previously been exposed to the low dose of bee venom experienced less hypothermia and were three times as likely to survive than the mice in the control group.

Further testing sought to find out whether IgE antibodies were required for protection. By using three types of mice with genetic mutations that blocked or inhibited the IgE antibodies, the researchers were able to confirm that a low dose of bee venom did not necessarily confirm protection of a later lethal dose. The find suggests that the immune response is linked with IgE signaling and mast cell activation.

"That was pretty exciting for us," said Thomas Marichal, a postdoctoral scholar and co-lead author of the study. "It was the first time we could see a beneficial function for these IgE antibodies."

Dr. Stephen Galli, the co-senior author of the study, said: "Our findings support the hypothesis that this kind of venom-specific, IgE-associated, adaptive immune response developed, at least in evolutionary terms, to protect the host against potentially toxic amounts of venom, such as would happen if the animal encountered a whole nest of bees, or in the event of a snakebite."

The research is published in the journal Immunity.