by Sharrada Subramaniam
How often do you suffer from an annoying runny nose, sneezing, watery eyes, or hives on your skin? The common cold shares many similar symptoms; however, what goes unnoticed very often is the underlying allergy. An allergy is a disorder of the immune system whereby the body overreacts to the allergen (substance causing the allergy)
An allergen could be an airborne particle (e.g., house dust mites or pollen), a food allergen (commonly peanuts, milk or seafood), and other proteins such as natural rubber latex, animal dander, toxins from insect stings or drugs (e.g., penicillin or aspirin).
An allergic response can range anywhere from being mild and hardly noticeable, to dangerous and life threatening. Common allergic symptoms include sneezing, watery eyes and itching, while severe allergic responses can lead to breathing difficulties (asthma) due to narrowing of the airways or excess mucus production. The most severe, often life threatening, form of an allergy is anaphylaxis, which leads to a systemic response affecting major body systems.
Worldwide statistics from the American Academy of Allergy, Asthma, and Immunology (AAAAI) show that up to 40% of the world population is sensitised to foreign antigens, while 10-30% of the population amounting to hundreds of millions of people are affected by allergic rhinitis [1,2]. Three hundred million others suffer from asthma . For the last 50 years, the prevalence of allergies has shown an increasing trend .
Risk factors and causes
In Malaysia, we are frequently exposed to dust mites, pollen, and spores. While many of us are immune to these harmless allergens, they trigger an allergic reaction in others. It is not fully understood why some people respond to the allergens, but not others, although genetics and environmental factors may play a role.
The genetic predisposition to have an allergic disease is 70% if an identical twin has it, and 40% for non-identical twins . Some initial studies showed that early contact with airborne allergens led to an increased likelihood of atopic disease later in life ; however there are contradictory views.
Atopy is a condition whereby individuals are more likely to develop an allergic response to allergens. Atopic individuals have a higher level of serum Immunoglobulin E (IgE) antibody compared to healthy people. Genetic and linkage studies have identified candidate genes and gene cluster patterns that are present in regions of particular chromosomes that may be able to explain these differences.
Some allergies are present from a young age while others can be developed with time. Overexposure to an allergen for a prolonged period of time can lead to a process of sensitisation to the allergen. Children who grow up being near to cats and dogs whose dander is a common cause of allergies are at a higher risk of developing an atopic allergy . Hence, environmental factors play a pivotal role in allergic diseases.
More than two decades ago, an epidemiological study proposed the “Hygiene Hypothesis” which suggested that the occurrence of hay fever in a family with children was inversely proportional to the household size . Children who were exposed to dirtier living conditions when they were young were less likely to develop certain allergies when they were older. Instead, children who contracted fewer childhood infections may have an inefficient maturation of the immune system and may be more susceptible to allergies . Different versions of this hypothesis were formulated years later, pointing to the link between the lack of early exposure to parasites and other microorganisms and the likelihood of allergic diseases.
The main player in the allergic response – IgE
First described in the 1960s by Kimishige Ishizika and colleagues , IgE belongs to a class of antibodies (proteins that are made when the body encounters a foreign antigen) together with other isotypes such as IgG, IgA, IgM and IgD. IgE, which is coincidentally the least abundant isotype in healthy humans, is the main player in the manifestation of an allergic response.
Why then do humans produce IgE antibody? There have been some suggestions that IgE have been evolutionarily produced for immunity against worm or parasitic infections in mammals, which used to be a severe problem in developing countries. Nonetheless, we still retain the ability to deal with a parasitic infection, and mount a defense reaction to eliminate the parasite. This beneficial role of IgE comes with a disadvantage: when IgE is released under non-threatening circumstances, the immune system recognises it as foreign, and thus, triggering allergic symptoms (Figure 1).
up to 40% of the world population is sensitised to foreign antigens, while 10-30% of the population amounting to hundreds of millions of people are affected by allergic rhinitis
An acute allergic response is an immediate response to the allergen which can bring about a localised (e.g., rhinorrhea, or eczema) or systemic reaction (e.g., anaphylaxis). This early stage response stems from activated mast cells that release their contents leading to the various symptoms. The late phase allergic response, which happens hours later is due to the recruitment of specialist cells to the site of encounter with the antigen.
Diagnosis, treatment and prevention
Nowadays, a simple skin or blood test can often reveal the allergenic status of a person to common allergens or to confirm suspected allergens. A tiny amount of the antigen is placed on the skin or below it, and any signs of inflammation are observed. IgE levels can also be measured from blood samples.
The best way forward in allergy prevention is avoiding the antigen. Firstly, one needs to identify the allergen, which may prove more challenging if it is not a common allergy. Very often, a change of lifestyle can help avoid common allergic attacks. This may include using “allergen impermeable” covers on bedding, keeping humidity low and avoiding close proximity with cats or dogs in the early years .
It is also very important to be prepared for the symptoms that may appear and have the necessary precautions taken. For those with a risk of an anaphylactic shock, having handy a dose of adrenaline may save a life. It is equally important for asthmatic patients to have their inhalers with them at all times too.
While a number of treatment options are available, nearly all of them target the symptoms rather than the prevention of the allergy. Anti-histamines, anti-inflammatory drugs, bronchodilators as well as decongestants are among more commonly used prescriptions to relieve common allergic symptoms such as rhinitis, hives, and asthma attacks due to bronchial constriction.
While scientists understand a lot about the production of IgE, as well as the cellular and molecular pathways involved, a complete understanding of this complicated “allergic response” is still lacking. New generation drugs are targeted to inhibit the production of IgE, rather than just alleviating the symptoms. Research in the field is faced with many limitations due to the scarcity of IgE, the rarest immunoglobulin isotype. Nonetheless, this is a hot topic in immunology today, as drugs which are able to inhibit IgE production could bring relief to millions of people worldwide.
 Pawankar et al. (2012) World Health Organization
 Galli (2000) Curr Biol. 10:R93-R95
 Soothill et al. (1976) Clin Allergy. 6:305-319
 Warner et al. (1990) Pediatr Allergy Immunol. 1:79-86
 Strachan (1989) BMJ, 299:1259-1260
 Holt et al. (1999) Nature. 402:B12–B17
 Ishizaka et al. (1966) J Immunol, 97:75-85
 Janeway et al. (2001) Immunobiology, Garland Science.
About the Author
SHARRADA SUBRAMANIAM is a final year A*STAR scholar at Singapore Immunology Network/NTU pursuing a PhD on the regulation of allergic diseases. Her work focuses on identifying and characterising the key players in an allergic response using murine models. She obtained her BSc (Hons) Biomedical Sciences at the University of Manchester, United Kingdom in 2010. Prior to that, she studied at Wesley Methodist School and Tunku Abdul Rahman college in Kuala Lumpur. Find out more about Sharrada at http://www.scientificmalaysian.com/members/sharrada/