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Genetics
Allergic diseases are strongly familial: identical twins are likely to have the same allergic diseases about 70% of the time; the same allergy occurs about 40% of the time in non-identical twins.[50] Allergic parents are more likely to have allergic children,[51] and those children's allergies are likely to be more severe than those in children of non-allergic parents. Some allergies, however, are not consistent along genealogies; parents who are allergic to peanuts may have children who are allergic to ragweed. It seems that the likelihood of developing allergies is inherited and related to an irregularity in the immune system, but the specific allergen is not.[51]
The risk of allergic sensitization and the development of allergies varies with age, with young children most at risk.[52] Several studies have shown that IgE levels are highest in childhood and fall rapidly between the ages of 10 and 30 years.[52] The peak prevalence of hay fever is highest in children and young adults and the incidence of asthma is highest in children under 10.[53]
Overall, boys have a higher risk of developing allergies than girls,[51] although for some diseases, namely asthma in young adults, females are more likely to be affected.[54] These differences between the sexes tend to decrease in adulthood.[51]
Ethnicity may play a role in some allergies; however, racial factors have been difficult to separate from environmental influences and changes due to migration.[51] It has been suggested that different genetic loci are responsible for asthma, to be specific, in people of European, Hispanic, Asian, and African origins.[55]
Hygiene hypothesis
Main article: Hygiene hypothesis
Allergic diseases are caused by inappropriate immunological responses to harmless antigens driven by a TH2-mediated immune response. Many bacteria and viruses elicit a TH1-mediated immune response, which down-regulates TH2 responses. The first proposed mechanism of action of the hygiene hypothesis was that insufficient stimulation of the TH1 arm of the immune system leads to an overactive TH2 arm, which in turn leads to allergic disease.[56] In other words, individuals living in too sterile an environment are not exposed to enough pathogens to keep the immune system busy. Since our bodies evolved to deal with a certain level of such pathogens, when they are not exposed to this level, the immune system will attack harmless antigens and thus normally benign microbial objects—like pollen—will trigger an immune response.[57]
The hygiene hypothesis was developed to explain the observation that hay fever and eczema, both allergic diseases, were less common in children from larger families, which were, it is presumed, exposed to more infectious agents through their siblings, than in children from families with only one child. The hygiene hypothesis has been extensively investigated by immunologists and epidemiologists and has become an important theoretical framework for the study of allergic disorders. It is used to explain the increase in allergic diseases that have been seen since industrialization, and the higher incidence of allergic diseases in more developed countries. The hygiene hypothesis has now expanded to include exposure to symbiotic bacteria and parasites as important modulators of immune system development, along with infectious agents.
Epidemiological data support the hygiene hypothesis. Studies have shown that various immunological and autoimmune diseases are much less common in the developing world than the industrialized world and that immigrants to the industrialized world from the developing world increasingly develop immunological disorders in relation to the length of time since arrival in the industrialized world.[58] Longitudinal studies in the third world demonstrate an increase in immunological disorders as a country grows more affluent and, it is presumed, cleaner.[59] The use of antibiotics in the first year of life has been linked to asthma and other allergic diseases.[60] The use of antibacterial cleaning products has also been associated with higher incidence of asthma, as has birth by Caesarean section rather than vaginal birth.[61][62]
Stress
Chronic stress can aggravate allergic conditions. This has been attributed to a T helper 2 (TH2)-predominant response driven by suppression of interleukin 12 by both the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. Stress management in highly susceptible individuals may improve symptoms.[63]
Other environmental factors
International differences have been associated with the number of individuals within a population have allergy. Allergic diseases are more common in industrialized countries than in countries that are more traditional or agricultural, and there is a higher rate of allergic disease in urban populations versus rural populations, although these differences are becoming less defined.[64]
Alterations in exposure to microorganisms is another plausible explanation, at present, for the increase in atopic allergy.[32] Endotoxin exposure reduces release of inflammatory cytokines such as TNF-α, IFNγ, interleukin-10, and interleukin-12 from white blood cells (leukocytes) that circulate in the blood.[65] Certain microbe-sensing proteins, known as Toll-like receptors, found on the surface of cells in the body are also thought to be involved in these processes.[66]
Gutworms and similar parasites are present in untreated drinking water in developing countries, and were present in the water of developed countries until the routine chlorination and purification of drinking water supplies.[67] Recent research has shown that some common parasites, such as intestinal worms (e.g., hookworms), secrete chemicals into the gut wall (and, hence, the bloodstream) that suppress the immune system and prevent the body from attacking the parasite.[68] This gives rise to a new slant on the hygiene hypothesis theory—that co-evolution of humans and parasites has led to an immune system that functions correctly only in the presence of the parasites. Without them, the immune system becomes unbalanced and oversensitive.[69] In particular, research suggests that allergies may coincide with the delayed establishment of gut flora in infants.[70] However, the research to support this theory is conflicting, with some studies performed in China and Ethiopia showing an increase in allergy in people infected with intestinal worms.[64] Clinical trials have been initiated to test the effectiveness of certain worms in treating some allergies.[71] It may be that the term 'parasite' could turn out to be inappropriate, and in fact a hitherto unsuspected symbiosis is at work.[71] For more information on this topic, see Helminthic therapy.
