General and specific IgE. Diseases and conditions

General and specific IgE. Diseases and conditions accompanied by changes in total IgE levels

mmunoglobulin E (IgE)

Immunoglobulin E (IgE) is a class of immunoglobulins found in normal amounts in blood serum and secretions. IgE was first isolated in the 1960s from the serum of patients with atopy and multiple myeloma. In 1968, the WHO designated IgE as an independent class of immunoglobulins. According to the WHO, 1 IU/ml (IU – international unit) corresponds to 2.4 ng. Typically, IgE concentration is expressed in IU/ml or kU/L (kU – kilo unit).

In normal conditions, IgE comprises less than 0.001% of all serum immunoglobulins.

Age groupsIgE (kU/L)
Up to 1 year0 – 15
1 year-6 years0 – 60
6 -10 years0 – 90
10 -16 years0 – 200
Adults0 – 100

The structure of IgE is similar to that of other immunoglobulins and consists of two heavy and two light polypeptide chains. They are grouped into complexes called domains. Each domain contains approximately 110 amino acids. IgE has five such domains unlike IgG, which has only four domains. By physicochemical properties, IgE is a glycoprotein with a molecular weight of approximately 190,000 daltons, consisting of 12% carbohydrates. IgE has the shortest half-life (2-3 days) among all immunoglobulins, the highest catabolic rate, and the lowest synthesis rate (2.3 μg/kg per day). IgE is mainly synthesized by plasma cells localized in mucous membranes. The main biological role of IgE is its unique ability to bind to the surface of mast cells and human basophils. Each basophil surface contains approximately 40,000 – 100,000 receptors that bind between 5,000 and 40,000 IgE molecules.

Degranulation of mast cells and basophils occurs when two membrane-bound IgE molecules bind to an antigen, which in turn “switches on” sequential events leading to the release of inflammatory mediators.

In addition to participating in type I (immediate) allergic reactions, IgE is involved in protective anti-helminthic immunity due to cross-linking between IgE and helminth antigens. The latter penetrates the mucous membrane and settles on mast cells, causing their degranulation. Inflammatory mediators increase the permeability of capillaries and mucous membranes, causing IgG and leukocytes to exit the bloodstream. Eosinophils attach to IgG-coated helminths, releasing the contents of their granules and thereby killing the helminths. IgE can be detected in the human body as early as the 11th week of intrauterine development. IgE levels in blood serum gradually increase from birth to adolescence. In old age, IgE levels may decrease.

In clinical diagnostic laboratory practice, the determination of total and specific IgE is carried out for their use as independent diagnostic indicators. The main diseases and conditions accompanied by changes in total

IgE levels in blood serum are listed in Table 2.

Table 2: Diseases and Conditions Accompanied by Changes in Total IgE Levels in Blood Serum

Diseases and ConditionsPossible Causes
I. Elevated IgE LevelsAllergic diseases mediated by IgE antibodies: Atopic diseases: Allergic rhinitis, Atopic bronchial asthma, Atopic dermatitis, Allergic gastroenteropathyAnaphylactic diseases: Systemic anaphylaxis, Urticaria – angioedema
Multiple allergens: Pollens, Dust mites, Epidermal, Food, Medications, Chemical substances, Metals, Foreign proteins
Allergic bronchopulmonary aspergillosis
Helminth infections
IgE antibodies associated with protective immunity
Hyper-IgE syndrome (Job syndrome)
T-suppressor defects
Selective IgA deficiency
Wiskott-Aldrich syndrome
Thymic aplasia (DiGeorge syndrome)
IgE myeloma
Reaction “graft versus host”
II. Reduced Total IgEAtaxia-telangiectasia
T-cell defects

Table 3: Total IgE Values in Blood Serum in Some Pathological Conditions (Adults)

Pathological ConditionsIgE Levels (kU/L)
Allergic rhinitis120 – 1000 kU/L
Atopic bronchial asthma120 – 1200 kU/L
Atopic dermatitis80 – 14000 kU/L
Allergic bronchopulmonary aspergillosis: – Remission – Exacerbation80 – 1000 kU/L 1000 – 8000 kU/L
Hyper-IgE syndrome1000 – 14000 kU/L
IgE myeloma15000 kU/L and above

Interpretation Features and Diagnostic Limitations of Total IgE

  • Approximately 30% of patients with atopic diseases have total IgE levels within normal range.
  • Some asthmatic patients may have increased sensitivity to only one allergen (antigen), resulting in normal total IgE levels, while skin testing and specific IgE are positive.
  • Total IgE concentration in blood serum also increases in non-atopic conditions (especially in helminth infections, certain forms of immunodeficiencies, and bronchopulmonary aspergillosis), with subsequent normalization after appropriate treatment.
  • Chronic recurrent urticaria and angioedema are not mandatory indications for determining total IgE, as they usually have a non-immune nature.
  • Normal range boundaries defined for Europeans may not be applicable to representatives of regions endemic to helminth infections.

Features of Interpretation and Diagnostic Limitations of Specific IgE

  • The availability of specific IgE determination should not overstate its diagnostic role in the evaluation of patients with allergies.
  • Detection of allergen-specific IgE (to any allergen or antigen) does not prove that this specific allergen is responsible for clinical symptoms; final conclusions and interpretation of laboratory data should only be made after comparison with the clinical picture and detailed allergological history.
  • Absence of specific IgE in peripheral blood serum does not exclude the possibility of involvement of an IgE-dependent mechanism, as local IgE synthesis and sensitization of mast cells may occur even in the absence of specific IgE in the bloodstream (e.g., allergic rhinitis).
  • Antibodies of other classes, especially IgG (IgG4), specific to the same allergen, may cause false-negative results.
  • Extremely high concentrations of total IgE, for example, in some patients with atopic dermatitis, may lead to false-positive results due to nonspecific binding to the allergen.
  • Identical results for different allergens do not indicate their equal clinical significance, as the ability to bind to IgE may vary among different allergens.

Considering all of the above, as well as the existing difficulties in the setup and interpretation of skin tests, let’s list the main indications and contraindications for prescribing specific allergological in vitro testing – determination of specific IgE (see Table 4).

Table 4: Indications and Contraindications for Determining Specific IgE

Differential diagnosis between IgE-dependent and non-IgE-dependent mechanisms of allergic reactions
Patients in whom it is impossible to identify the allergen anamnestically, using a diary, etc.
Patients with inadequate response to specific hyposensitization, prescribed based on skin test results
Dermographism and widespread dermatitis
Patients of pediatric and elderly age with skin hyporeactivity
Skin hyperreactivity
Patients for whom it is impossible to discontinue symptomatic therapy with drugs affecting the skin test results
Patient’s negative attitude towards skin tests
History of systemic allergic reactions to skin tests
Discrepancy between skin test results and history data and clinical picture
IgE-dependent food allergy
Need for quantitative assessment of allergen sensitivity and specificity
Total IgE levels in blood serum over 100 kU/L

Investigation is inappropriate:

In cases of atopic diseases with satisfactory results of specific therapy based on skin test results
In patients with non-IgE-dependent mechanisms of allergic reactions