Total IgE

The total concentration of immunoglobulin E in serum is for the most part increased in allergic patients, but normal total IgE levels do not rule out specific sensitization.

Causes of high IgE concentrations

• Allergies (peak values after exposure)
• Allergic bronchopulmonary aspergillosis (ABPA)
• Atopic dermatitis
• Parasitoses: echinococci, Fasciola hepatica, filariae, schistosomes, Strongyloides stercoralis, Toxocara canis, Trichinella spiralis
• Viral infections: hepatitis, HIV
• Nephrotic syndrome
• Lymphoproliferative diseases, Hodgkin's disease
• IgE myeloma (rare, very high values)
• Immunodeficiency, particularly hyper-IgE syndrome (rare, very high values)
• Wiskott-Aldrich syndrome

References / Links

Ebnöther M, Schoenenberger R. Eosinophilie - was kommt in Frage? Schweiz Med Forum 2005;5:735-41

Hamilton RG, Adkinson NF. Immunological tests for diagnosis and management of human allergic disease: Total and allergen-specific IgE and allergen-specific IgG. In: Manual of Clinical Laboratory Immunology 1997;109:881-92. American Society for Microbiology, Washington DC

Specific IgE

	Allergies in young children
	Rhinits / Cough / Asthma
	Food allergies
	Insect venom
	Occupational and industrial allergies
	Latex- and drug allergy

A negative result for specific IgE in serum does not entirely exclude sensitization. Mast cell-bound IgE cannot be measured in serum and is degraded less rapidly than free IgE in serum.

The findings of specific IgE for inhalant allergens and frequent food allergens coincide to a large extent with skin test findings.

The IgE concentration is not necessarily correlated with the severity of the symptoms. During therapy and hyposensitization there is no obligatory regression in specific IgE. They can therefore be used only to a limited extent as follow-up parameters. The same applies to allergen-specific IgG. However, the probability of an allergic disease increases with the concentration of specific IgE, with different cut-off values applied to various allergens (see below).

Classification of class-specific IgE

References / Links

Bircher AJ et al. Stellenwert und Indikation der Bestimmung spezifischer IgE- und IgG-Antikörper in der Allergiediagnostik. Schweiz Ärztezeitung 2001;82:1605-6

Kay AB. Allergy and allergic diseases. N Engl J Med 2001;344:30-7 und 109-13

Pepys J. "Atopy": a study in definition. Allergy 1994; 49:397-9

Wüthrich B et al. Prevalence of atopy and pollinosis in the adult population of Switzerland (SAPALDIA study). Swiss Study on Air Pollution and Lung Diseases in Adults. Int Arch Allergy Immunol 1995;106:149-56

Yunginger JW et al. Quantitative IgE antibody assays in allergic diseases. J Allergy Clin Immunol 2000;105:1077-84

http://www.immunocapinvitrosight.com

Cellular stimulation test (CAST, FlowCAST)

The CAST (Cellular Antigen Stimulation Test) measures the release of sulfidoleukotrienes (s-LT), after ex vivo stimulation of basophilic leukocytes by allergens. s-LT are released in allergic processes. In hymenoptera allergies the test can be superior to the detection of specific IgE in certain cases. Pseudoallergic reactions such as hypersensitivity to NSAIDs (aspirin intolerance) or certain food additives can be detected with CAST. The sensitivity however is limited (18 - 85%, depending on the allergen), with a specificity between 67 - 100%.

With FlowCAST, rather than s-LT release, it is the increased expression of CD63, CD203c or other proteins on the cell surface of basophilic leukocytes and mast cells that is measured flow cytometrically after incubation with allergens. Depending on the allergen, the sensitivity is from 50% (e.g. b-lactams, hymenoptera venom) up to 91% (e.g. latex), and the specificity > 90%.

After the administration of corticosteroids, cromoglycic acid or indomethacin blood samples should be taken for cellular stimulation tests no earlier than 24 h after the last dose. Antihistamines have no effect. Cellular stimulation tests are not suitable for investigating T-cell-mediated hypersensitivity reactions such as drug rash or contact allergies.

The test is no longer offered by Viollier. As an alternative we recommend the following reference laboratories. Appointments for examinations must be made in advance by telephone.

Hamilton RG et al. In vitro assays for the diagnosis of IgE-mediated disorders. J Allergy Clin Immunol 2004;114:213-25

Immunoprecipitins

In exogenous allergic alveolitis, specific precipitating IgG are formed to inhaled antigens. These can result in an immune complex reaction (type III). The disease typically occurs with the repeated, occupationally related inhalation of organic dust and thus is of significance for occupational medicine. Symptoms do not occur until some hours after exposure. Designations for the occupational groups concerned refer to relevant antigens at the work place. Typical antigens are mold spores from moist hay (farmer's lung) or cheese rind (cheese-washer's lung) as well as birds' feathers and feces (bird-fancier's lung).

Specific IgG can be detected in more than 90% of clinically affected patients, but also in 50% of exposed subjects who remain asymptomatic for a prolonged period. For this reason the isolated detection of specific IgG is insufficient for diagnosis. Multiple determinations increase the sensitivity.

The following criteria should be met:

• Demonstrated or probable exposure to organic dust
• Respiratory or systemic symptoms

References / Links

Minder S, Nicod LP. Exogen allergische Alveolitis (Hypersensitivitätspneumonitis. Schweiz Med Forum 2005;5:567-74

ECP: eosinophil cationic protein

Asthma is due to inflammation of the bronchi. It is caused, among other things, by eosinophilic granulocytes and their mediators. ECP is an eosinophilic mediator in preformed granules. Its increased secretion is associated with asthmatic disorders. The advantage of measuring ECP is a direct correlation with the inflammation processes. ECP is therefore used for monitoring activity and therapy in asthma.

ECP is only released from preactivated eosinophilic granulocytes on blood coagulation. In follow-up tests, only values that have been obtained under the same conditions (coagulation time and temperature) can be compared with one another. It should be noted that the state of activity of the granules in the peripheral blood need not necessarily be the same as in the target organ. There is also no correlation with the number of eosinophilic granulocytes in the peripheral blood.

References / Links

Tomassini M et al. Serum levels of eosinophil cationic protein in allergic diseases and natural allergen exposure. J Allergy Clin Immunol 1996;97:1350-5

Tryptase

Tryptase is an enzyme that derives from mast cells and basophilic granulocytes. a-tryptase, which is excreted continuously from mast cells, is distinguished from b-tryptase, which is released on degranulation as a result of anaphylaxis. The test system from Phadia does not distinguish the two types so that each time the total amount of tryptase is recorded.

In anaphylactic reactions the highest concentrations are measured about an hour after allergen contact. After a few hours tryptase returns to the baseline concentration.

Raised baseline tryptase concentrations are found in systemic mastocytosis, whereas with the purely cutaneous form (urticaria pigmentosa) mostly normal or only slightly raised values (up to 20 mg/L) are found. If raised tryptase values are found after an anaphylactic reaction, a further examination should be performed after a few days to determine the baseline value.

Hymenoptera venom allergy sufferers are liable to an increased risk of a severe allergic reaction to insect bites when they exhibit increased baseline tryptase values. Determination of the baseline value is therefore recommended in these patients.

References / Links

http://www.uni-duesseldorf.de/awmf/ll/061-018.htm.

http://www.aerztekammer-bw.de/25/10praxis/80dermatologie/0803.pdf

CCD

Many allergens are glycoproteins. Sugar epitopes can exhibit significant structural homologies and are therefore responsible for cross-reactivities between various allergens. These sugar epitopes care called CCD (= Cross-reactive Carbohydrate Determinants). A CCD IgE test can be indicated if in vitro results are not consistent with the clinical presentation, particularly if several positive results occur without clinical correlation. The determination of CCD IgE is recommended in the following situations:

• Sensitization to plant foods, particularly vegetables, fruit and peanuts
• Sensitization to latex in pollen allergy sufferers without latex exposure
• Sensitization to both bee and wasp venom

References / Links

van Ree R. Carbohydrate epitopes and their relevance for the diagnosis and treatment of allergic diseases. Int Arch Allergy Immunol 2002;129:189-97