Allergy Basics

Nomenclature by WAO/EAACI (World Allergy Organization/European Academy of Allergy and Clinical Immunotherapy)

Atopy : Atopy is a personal and/or familial tendency, usually in childhood or adolescence, to become sensitized and produce IgE antibodies in response to ordinary exposure to allergens, usually proteins. As a consequence, such individuals can develop typical symptoms of asthma, rhino-conjunctivitis, or eczema. The terms ‘atopy’ and ‘atopic’ should be reserved to describe the genetic predisposition to become IgE-sensitized to allergens commonly occurring in the environment and to which everyone is exposed but to which the majority do not produce a prolonged IgE antibody response. Thus, atopy is a clinical definition of an IgE antibody high-responder. The term atopy cannot be used until an IgE sensitization has been documented by IgE antibodies in serum or by a positive skin prick test. Allergic symptoms in a typical atopic individual can be referred to as atopic, e.g., atopic asthma. However IgE-mediated asthma in general should not be called atopic asthma. Neither a positive skin prick test nor presence of IgE antibody to a less common allergen, e.g. Hymenoptera sting or a drug, which are high dose exposures, is a diagnostic criterion for atopy.

Hypersensitivity : Hypersensitivity causes objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus that is tolerated by normal subjects.

Non-allergic hypersensitivity : Non-allergic hypersensitivity is the preferred term to describe hypersensitivity in which immunological mechanisms cannot be proven

Atopy is the propensity to produce IgE antibody to allergens (antigens that stimulate the production of IgE antibodies) that are commonly encountered in the general environment—for example, pollens, mites, and moulds. Atopy is usually identified by the provocation of one or more immediate “weal and flare” responses in the skin to extracts of common inhalant allergens. Specific IgE antibody to common inhalant allergens can also be found in the serum samples of atopic individuals, who may also have a raised serum concentration of total IgE. Nonetheless, the atopic “patient” may or may not has clinical symptoms in their daily living.  The development of atopy can be influenced by both genetic and environmental factors. It is found that if both parents are allergic the risk of allergy in the offspring is 75%; if one parent is allergic the risk is 50%. The risk in the population is 10-20%.

Allergens : Allergens are antigens which cause allergy. Most allergens reacting with IgE and IgG antibody are proteins, often with carbohydrate side chains, but in certain circumstances pure carbohydrates have been postulated to be allergens. In rare instances low molecular weight chemicals, eg, isocyanates and anhydrides acting as haptens, are still referred to as allergens for IgE antibodies. In the case of allergic contact dermatitis, the classical allergens are low molecular weight chemicals, eg, chromium, nickel and formaldehyde, reacting with T cells.

Allergy : Allergy is a hypersensitivity reaction initiated by immunological mechanisms. Allergy can be antibody-or cell-mediated. In the majority of cases the antibody typically responsible for an allergic reaction belongs to the IgE isotype and these individuals may be referred to as suffering from an IgE-mediated allergy. Not all IgE associated ‘allergic’ reactions occur in ‘atopic’ subjects. In non-IgE-mediated allergy the antibody can belong to the IgG isotype, e.g., anaphylaxis due to immune complexes containing dextran, and the classical, nowadays rare, serum sickness previously referred to as a Type III reaction. Both IgE and IgG antibodies are found in allergic bronchial pulmonary aspergillosis (ABPA). Allergic contact dermatitis is representative of allergic diseases mediated by lymphocytes.

Allergy is not a disease itself, but a mechanism leading to disease. In clinical practice, allergy manifests in form of various different conditions such as anaphylaxis, urticaria, angioedema, allergic rhino-conjunctivitis, allergic asthma, serum sickness, allergic vasculitis, hypersensitivity pneumonitis, atopic dermatitis (eczema), contact dermatitis and granulomatous reactions, as well as the colourful spectrum of food- or drug – induced hypersensitivity reactions. Allergies can be seen in almost every organ. Most commonly, however, it is the skin and the mucous membranes that are involved since they represent the frontier between the individual organism and its environment.

Classification of environmentally induced disorders and position of allergy

 

Immunoglobulin E (IgE) : It is one of the five antibody classes, IgM, IgD, IgG, IgA and IgE, in mammals. There are four subclasses of IgG (IgG1-4) and two of IgA (IgA1, IgA2), making a total of 9 nine different classes including the subclasses in humans.

Antibodies of the IgE class are central to the allergic response. They are synthesized and secreted by IgE-expressing B cells that have differentiated into IgE-secreting plasma cells. IgEs bind to mast cells and antigen-presenting cells bearing the high-af nity IgE receptor, FcεRI, to sensitize the cells for allergen activation. Allergen-activated mast cells release the physiologically potent molecules that cause the symptoms of allergy. The activated antigen-presenting cells stimulate T helper 2 (Th2) cells, which in turn induce the production of more allergen-specific antibodies in a positive feedback loop primed by allergen.  Antibodies of the same or cross-reacting specificity, but another antibody class can compete with IgE for antigen binding to prevent or suppress the allergic response. This may occur in specific allergen immunotherapy, which stimulates a modified Th2 response, causing a massive up-regulation of IgG4 and IgA2.  It is thought that immune deviation to IgG4 and IgA2 allergen specificities may contribute to the success of specific allergen immunotherapy.

Structural and glycosylation properties of immunoglobulins: Depiction of the structure and glycosylation sites (indicated by amino acid location) for human IgM, IgG, IgD, IgE, IgA2, and IgA2 (Annu Rev Immunol 2007;25:21-50)

 

Allergen cross-reactivity

Allergen cross-reactivity refers to the concordance of IgE reactivity between two or more crude extracts from different species due to the presence of homologous proteins that share antibody-binding epitopes. In the attempt to control allergic disease by reducing allergen exposure, it is necessary to minimize exposure to all sources of the sensitizing and the cross-reacting allergens.

Allergy plays an important role in some asthmatics for some of the time. In the majority of cases of eczema and urticaria, allergy probably only plays a small role. Rhinitis (inflammation of the nose) can have both allergic and nonallergic causes. Seasonal allergic rhinitis (hay fever) is entirely due to allergy. In chronic allergic rhinitis, the allergens are usually the house-dust mite and animal danders. However, many cases of chronic rhinitis have no allergic cause (this is sometimes called “vasomotor rhinitis”). In patients with food intolerance and drug reactions, allergy is often unproven. There is no evidence that multiple chemical sensitivity has an allergic basis.

 

Allergy mechanism

Pathophysiology of allergic rhinitis. The first stage of development of allergic rhinitis involves antigen processing and the production of specific immunoglobulin E (IgE) antibodies, which attach to mast cells, basophils, and other inflammatory cells. On subsequent exposure to the same allergen, IgE receptors on the surface of mast cells are cross-linked, which leads to the degranulation of these cells and to the release of preformed and newly synthesized mediators responsible for symptoms of the disease. Recruitment of inflammatory cells to the nasal mucosa also occurs, as does a resultant state of chronic inflammation with a heightened state of reactivity to specific and nonspecific stimuli—a hallmark of allergic nasal disease. In addition to the early and late inflammatory responses, exposure to allergen leads to a secondary immune response with increased production of specific IgE and a perpetuation of the state of susceptibility to allergen. (From Naclerio RM: Allergic rhinitis. N Engl J Med 1991;325:860.)

Allergy prevalence in Hong Kong and the common allergens

Allergy is a common disease with a documented increase in prevalence in different areas of the world.  According to HKIA, about 33% of children aged 6 to 7 suffered from rhinitis, one of ten secondary school children have asthma and up to 15% of them have atopic dermatitis (HK Med J 2016; 22:279-285).  A survey done with 7393 children aged 14 and below in HK revealed about 4.8% of them have adverse reactions to foods (Asian Pac J Allergy Immunol 2012; 30: 275-284).  Skin prick tests performed on 977 patients suffering from chronic rhinitis has found the commonest allergens which the patients sensitized were dust mites, including both the house dust mites Dermatophagoides pteronyssinus and Dematophagoides farina (> 60%), and the storage mite Blomia tropicalis (40%).  Other common allergens include cockroach and cat.  Dog, pollens and molds only account for less than 5% (HK Med J 2007; 13:131-136).  About half of the tested patients were sensitized to more than one allergens, who were also likely to have earlier age of onset of symptoms, higher chance of association with asthma, and more severe rhinitis symptoms.

Allergen

No. of patient tested

Positive reaction (Number)

Percentage of positive reaction

Dust mites (including Dp, Df and Bt)

977

620

63%

 ​​ ​​​​ Dp and Df

977

613

63%

 ​​ ​​​​ Blomia tropicalis

364

141

39%

Cockroach

977

223

23%

Cat

977

138

14%

Dog

977

50

5%

Mould mix

977

30

3%

 ​​ ​​​​ Aspergillus mix

591

29

5%

Pollen mix

546

21

4%

 ​​ ​​​​ Bermuda grass

537

9

2%

Dp: Dermatophagoides pteronyssinus

HK Med J 2007; 13: 131-136

Df: Dermatophagoides farina

Bt: Blomia tropicalis

The high prevalence of sensitization to both house dust mites (Dp + Df) and storage mites Blomia tropicalis has also been found in Guangzhou, Southern China that a retrospective review of skin prick test result was done on 2,136 children with allergic rhinitis.  It showed 90.08% of the allergic rhinitis patients were sensitized to dust mites and among them, 90.82% were sensitized to more than one allergen.

Allergen

No. of patient tested

Positive reaction (Number)

Percentage of positive reaction

Dermatophagoides pteronyssinus

2,136

1,990

93.16%

Dermatophagoides farina

2,136

1,842

86.23%

Blomia tropicalis

2,136

870

40.73%

German cockroach

2,136

419

19.62%

Cat

2,136

434

20.23%

Dog

2,136

413

19.34%

Alternaria tenuis

2,136

210

9.83%

Artemisia argyi

2,136

108

5.06%

Ragweed

2,136

106

4.96%

Timothy grass

2,136

93

4.35%

Birch

2,136

68

3.18%

J Allergy Ther 2014; ​​ 5: 178-183

Based on these results, screening allergic patients with six to eight allergens should be good enough to identify more than 90% of the sensitization among children in Hong Kong. This is in fact in agreement with the practice in Europe where less than 10 allergens were routinely used in the clinics, including several pollens which are not important in Hong Kong (Allergy 2005: 60: 1287–1300).

WhatsApp WhatsApp T-Medi