Peanuts. Bees. Pets. Trees. For most people, these things are harmless parts of everyday life. But for allergy sufferers, plenty of seemingly innocuous items can be unbearably irritating and even lethal. Now scientists have uncovered a possible molecular reason why humans evolved to have allergies, and it could lead to new ways to treat the troublesome condition.
Allergies are immune reactions gone wrong that can cause problems from upset stomachs and asthma attacks to deadly anaphylactic shock. While we've gotten pretty good at understanding what triggers allergies and how to mitigate them, researchers have been unsure why we even have allergies in the first place.
A new computer-powered analysis of the proteins involved in allergic responses supports the theory that a natural immune response that evolved to fight parasites is being misdirected in allergy sufferers against otherwise harmless triggers.
Humans have likely cohabitated with parasitic worms for our entire evolutionary history. But during recent decades, such parasites have largely disappeared in parts of the developed world, while allergy rates have risen. The "hygiene" hypothesis, now several decades old, suggests that with no parasites to fight, the immune system doesn't know when to quit and ends up targeting allergens.
"It's a very aggressive response, with the idea to quickly get rid of the parasite, and it's mediated by an antibody called IgE," says Nick Furnham at the London School of Hygiene & Tropical Medicine. "This is the same branch of the immune system which is elicited when you have an allergic response."
People don't develop long-term allergies to parasites, though, which suggests that the body has some mechanism for turning off the parasite-targeting immune reaction.
"It's poorly understood just how that mechanism works, but the immune system gets kind of played down when you have a prolonged parasitic infection, so you don't get a long-term, crazy overreaction," Furnham says.
Because allergens aren't really parasites, it may be that once they are targeted, the mechanisms to ratchet down the response never kick in, leading to lasting allergies with unfortunate results. Some allergies can prove fatal, but even relatively harmless versions can be so infuriating that they lead some people to extreme behaviors—like tracking every single sneeze for five years to identify and fix a pollen allergy.
Why would parasite-fighting systems turn their attention to allergens in the first place? Furnham and colleagues put one theory to the test. "There must be some form of molecular similarity operating between the proteins that cause allergies and the proteins that your immune system is expecting to see in parasites like worms," he says.
The team looked for and found molecular similarities between the proteins in common parasites and the ones in pollen known to cause allergies. They then predicted regions of the parasite proteins that likely shared similarities with the regions of the allergens where the IgE antibody binds.
Using blood serum from parasite-infected people in Ghana, experimental studies finally revealed the first known example of a pollen-like protein present in a parasitic worm that gets targeted by IgE.
The study methods, described this week in PLOS Computational Biology, may yield new tools for more easily identifying the specific proteins in foods and the environment that cause allergies. It could also inform future ways to intervene and help allergy sufferers with techniques like microexposure. This involves giving someone very small amounts of the thing they are allergic to, in hopes of building up immunity. The method has shown some success in training away reactions like peanut allergies.
"This is … in a way mimicking having a long-term parasitic exposure," Furnham explains. "So if you knew what these particular proteins were that were causing the immune response to the parasite, you could extract them and perhaps make synthetic versions for use as a way of dosing people for immunotherapy. But there are difficulties, ethical and practical, so I think that's quite a long way off."