Chapter 25
Clinical laboratory assessment of immediate-type hypersensitivity

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Clinical laboratory analyses aid in the diagnosis and management of human allergic (IgE-dependent) diseases. Diagnosis of immediate-type hypersensitivity begins with a thorough clinical history and physical examination. Once symptoms compatible with an allergic disorder have been identified, a skin test, blood test, or both for allergen-specific IgE antibodies provide confirmation of sensitization, which strengthens the diagnosis. Skin testing provides a biologically relevant immediate-type hypersensitivity response with resultant wheal-and-flare reactions within 15 minutes of allergen application. Allergen-specific IgE antibody in serum is quantified by using 3 laboratory-based autoanalyzers (ImmunoCAP, Immulite, and HYTEC-288) and novel microarray and lateral-flow immunoassays. Technologic advances in serologic allergen-specific IgE measurements have involved increased automation, with enhanced reproducibility, greater quantification, lower analytic sensitivity, and component-supplemented extract-based allergen use. In vivo provocation tests involving inhalation, ingestion, or injection of allergens serve to clarify discordant history and skin- or blood-based measures of sensitization. Other diagnostic allergy laboratory analyses include total and free serum IgE measurement, precipitating IgG antibodies specific for organic dusts, mast cell tryptase, and indicator allergen analyses to assess indoor environments to promote patient-targeted allergen avoidance programs. A critique is provided on the predictive utility of serologic measures of specific IgE for food allergy and asthma. Reasons for the lack of clinical utility for food-specific IgG/IgG4 measurements in allergy diagnosis are examined. When the specific IgE measures are inconsistent with the clinical history, they should be confirmed by means of repeat and alternative method analysis. Ultimately, the patient's clinical history remains the principal arbiter that determines the final diagnosis of allergic disease.

Section snippets

IgE properties

The reagin in serum that mediates the immediate-type wheal-and-flare reaction was identified as IgE in 1967.1, 2 The properties of human IgE are described in Table I. IgE (approximately 190,000 d) circulates as a monomer at a serum concentration that is highly age dependent. It constitutes approximately 0.0005% of the total serum immunoglobulins in adults.3 Cord blood levels of IgE remain low (<2 kU/L [<4.8 μg/L]) because IgE does not cross the placental barrier in significant amounts. Mean

Allergens

Several hundred allergenic proteins, (glycoproteins and lipoproteins), are extracted from well-defined (usually biological) sources, including weed, grass, and tree pollens and animal dander, molds, house dust mites, parasites, insect venoms, occupational allergens (eg, natural rubber latex), drugs, and foods.6 These allergens elicit IgE antibody production when introduced into an immunocompetent and genetically predisposed host. Individual allergenic proteins can be identified by using IgE

Diagnostic algorithm for allergic disease

The diagnosis of allergic disease begins with a thorough clinical history and physical examination.9, 10 The signs and symptoms associated with the various allergic disorders are extensively discussed in chapters 8-14. Once the history has been collected, one of several primary confirmatory tests for sensitization can be performed to detect allergen-specific IgE in the skin or blood. Because the history is viewed by many as the arbiter of the diagnostic test's performance, a subject with a

Diagnostic skin testing

Skin testing is one of 2 primary confirmatory tests for allergen-specific IgE antibody that are used in the diagnosis of human allergic disease. An epicutaneous administration (previously referred to as a prick/puncture) or an intradermal injection can both be used to apply allergen in the form of an extract to the skin.13

Diagnostic immunology laboratory tests

Although the presence of allergen-specific IgE antibody is necessary but not sufficient for clinically manifested allergic disease, it has become the primary clinical laboratory measurement used in the diagnosis of human allergic disease. Most clinical laboratories offer a number of additional serologic tests that can be useful in selected circumstances for the diagnosis or management of patients with type 1 hypersensitivity. These measurements include total serum IgE, the Hymenoptera

In vivo diagnostic provocation testing

When discordance occurs between the clinical history and primary diagnostic confirmatory test results, one of several provocation tests might be performed.13 Bronchial and nasal provocation challenges are techniques used to identify a relationship between an inhaled substance and a change in the patient's bronchial or nasal physiology. A DBPCFC is used to evaluate patients who have experienced food-induced gastrointestinal reactions (eg, nausea, colic, vomiting, and diarrhea) that can occur

Indoor aeroallergen testing

Avoidance by separating the allergic patient from the allergen source is possibly the least expensive and most effective mode of treatment for allergic disease, when it is achievable. Knowledge about the levels of allergen in an environment can support the decision to initiate expensive alterations of their home, school, or workplace to facilitate avoidance of indoor aeroallergens. Some clinical laboratories perform environmental allergen quantification in which an air sample or a surface dust

Outdoor aeroallergen testing

Most major cities across the United States have an aerobiology monitoring station with a collection device on a platform or roof top, typically 1 story off the ground (eg, 13 feet). Ideally it is in an open space distant from trees, which can bias the aeroallergen results. The Rotorod Sampler (Sampling Technologies, St Louis Park, Minn) is one widely used rotating-arm impactor that recovers airborne particles on 2 rapidly moving plastic collector rods.71, 72 It contains a pair of 1.59-mm-wide

Conclusion

A number of analytic measurements are used to promote more accurate diagnosis and better management of allergic subjects. The clinician should remember that all in vivo and serologic analyses are subject to inherent variation and potential interference. Thus it is prudent to question the validity of any in vivo or laboratory test that is inconsistent with a carefully collected clinical history. One should repeat in vivo testing on a different day or perform serologic testing with a new blood

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    Disclosure of potential conflict of interest: R. G. Hamilton has declared that he has no conflict of interest.

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