Are allergies trying to protect us from ourselves?

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I have a love/hate relationship with spring, thanks to the aggravating bouts of hay fever that transform me into a faucet for pretty much the entire season. So I’ll admit I was a little skeptical when my editor at Scientific American asked me last week if I wanted to write about a new paper coming out in Nature suggesting that allergies may actually be a good thing. But always curious, I said sure.

Turns out it’s a fascinating—and pretty convincing—read. It’s dense, but the lead author, Yale immunobiologist Ruslan Medzhikov, was kind to take a good two hours out of his day on Monday to explain some of the gnarlier concepts to me. (Medzhikov is fascinating—you can read more about him in this profile published in Disease Models & Mechanisms.)

Medzhikov’s basic argument is that there is a convincing body of research suggesting that allergies have beneficial effects. They break down the toxic components of bee, snake, scorpion and gila monster venom, for instance, and our allergic reactions to tick saliva prevent the parasites from feeding.

Ultimately, all allergic responses work towards a common goal: avoidance and expulsion, Medzhitov argues. As I explain in my piece,

More generally, hated allergic symptoms keep unhealthy environmental irritants out of the body, Medzhitov posits. “How do you defend against something you inhale that you don’t want? You make mucus. You make a runny nose, you sneeze, you cough, and so forth. Or if it’s on your skin, by inducing itching, you avoid it or you try to remove it by scratching it,” he explains. Likewise, if you’ve ingested something allergenic, your body might react with vomiting. Finally, if a particular place or circumstance ramps up your allergies, you’re likely to avoid it in the future. “The thing about allergies is that as soon as you stop exposure to an allergen, all the symptoms are gone,” he says.

Obviously, Medzhitov’s theory is just a theory, and it involves a lot of speculation (albeit informed speculation by a really smart guy). But some research suggests an association between allergy severity and cancer risk, in that people with more allergy symptoms are less likely to develop certain cancers. (One shouldn’t read too much into this though; some other factor may drive the association. Perhaps people who eat lots of eggs are more likely to have allergies but less likely to have cancer.) But all in all, I think Medzhitov’s idea does make sense and is well-supported, and most of the outside experts I spoke with agreed, though they did raise questions about some of the specifics.

One aspect of the theory that I didn’t mention in my piece is that it could explain a medical mystery: penicillin allergies. Medzhitov argues that in addition to protecting against venoms, vector-borne diseases and environmental irritants, allergies also evolved to protect against a class of toxins called haptens: proteins that bind to extracellular or membrane-bound proteins in the body, rendering them useless and ultimately causing all sorts of problems. As it turns out, in some people, the penicillin molecule undergoes transformation into a hapten. This transformation is very slow and inefficient—very few penicillin markers turn into haptens, which is a good thing because haptenated penicillin could be dangerous—but nevertheless, some people may develop allergic responses to these few haptenated penicillin molecules, and this can result in an allergic hypersensitivity to the drug, Medzhitov posits.

In the case of something like a penicillin allergy, management is fairly simple (though medically inconvenient): avoid penicillin. The problem today is that there may be millions of allergens in the form of environmental pollutants and irritants, and they may simply be unavoidable. This idea could help explain why allergic diseases have become more common in recent decades: We’re exposed to many more pollutants now than we were 50 years ago, and this chemical flurry could be dialing up our innate defense systems to a constant level of 11. An allergy may be protective, but “if it’s taken to an extreme, it is pathological,” Medzhitov says. I wonder, then, if we may have built ourselves a world that will forever make us sick.

Citations:

Palm, N., Rosenstein, R., & Medzhitov, R. (2012). Allergic host defences Nature, 484 (7395), 465-472 DOI: 10.1038/nature11047

Medzhitov, Ruslan (2011). Innovating immunology: an interview with Ruslan Medzhitov Disease Models & Mechanisms, 4 (4), 430-432 DOI: 10.1242/dmm.008151

Akahoshi M, Song CH, Piliponsky AM, Metz M, Guzzetta A, Abrink M, Schlenner SM, Feyerabend TB, Rodewald HR, Pejler G, Tsai M, & Galli SJ (2011). Mast cell chymase reduces the toxicity of Gila monster venom, scorpion venom, and vasoactive intestinal polypeptide in mice. The Journal of clinical investigation, 121 (10), 4180-91 PMID: 21926462

Wada T, Ishiwata K, Koseki H, Ishikura T, Ugajin T, Ohnuma N, Obata K, Ishikawa R, Yoshikawa S, Mukai K, Kawano Y, Minegishi Y, Yokozeki H, Watanabe N, & Karasuyama H (2010). Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks. The Journal of clinical investigation, 120 (8), 2867-75 PMID: 20664169

Sherman, P., Holland, E., & Sherman, J. (2008). Allergies: Their Role in Cancer Prevention The Quarterly Review of Biology, 83 (4), 339-362 DOI: 10.1086/592850

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