Allergy in an Evolutionary Framework

Abstract

Respiratory allergy including bronchial asthma and food allergy have gained epidemic character in the last decades in industrialized countries. Much has been learned with respect to the pathophysiology of allergic disease and this has facilitated specific therapies. Allergy is a chronic disease, and being so prevalent claims to search for evolutionary causes of the general susceptibility of humans as a species to react to environmental antigens in a Th2 type immune reaction with IgE production. In an evolutionary analysis of Allergy, necessary questions addressed in this review are “Why does IgE exist or why did IgE evolve?” as well as from the point of view of the mismatch hypothesis, “Why is there an Allergy epidemic?” Recent studies on the possible biological and protective role of IgE against parasites, arthropods, venoms or toxins are challenging the widely accepted definition of allergens as generally innocuous antigens. Combining the immunologic danger model and the toxin hypothesis for allergies, the allergic response could have evolved with an adaptive value and allergens could be proxies for other putative noxious agents. The last decades yielded with vast molecular data of allergens. With available bioinformatics tools, we therefore also describe that evolutionary theory could be applied to prevent allergy, estimate cross-reactivity, to design allergen-specific immunotherapy and to assess the risks of novel foods.

Appendix

Box 1: Some Evolutionary Principles Addressed in This Work

For reviews see (Williams and Nesse 1991; Nesse and Stearns 2008; Stearns 2012).

Proximate explanations are related to physiology and pathophysiology, those mechanisms, which all medical students learn. Evolutionary explanations deal with the question why concrete traits have evolved or why humans are vulnerable to certain diseases from an evolutionary point of view.

Co-evolution between parasites and hosts has shaped immune features and is thought to explain the anti-inflammatory power of chronic parasitism and species living within our microbiota. The new versions of the Hygiene Hypothesis give clear relevance to possible depletion or reduction of diversity of our microbiome causing vulnerability to chronic inflammatory disease.

Symptoms can be interpreted as defenses or defects. Defects are annoying, but their presence can be of survival value. This is interesting when analysing allergic symptoms. From an evolutionary perspective vulnerability to allergic symptoms could reflect evolved mechanism to get rid of parasites or noxious substances.

The thresholds for defense expression are set by the smoke-detector principle: When the cost of expressing a defense is low compared to the potential harm it protects against, false alarms are predicted to evolve. Allergic hypersensitivity leads to exaggerated symptoms, but these remember some of the defense mechanisms elicited by contact with pathogens or irritant, noxious substances.

Trade-offs are intrinsic to all designs and deal with evolutionary constraints and compromises. The allergic response comes with costly trade-offs nowadays but an evolutionary interpretation could give clues to increased biological efficacy in past or other environmental situations.

Mismatch between design and environment: Genetic design has evolved to cope with an expected environment. Rapid environmental changes produced by human activity are thought to be one of the reasons for the increasing prevalence of chronic inflammatory diseases and Allergies.