Page 1322 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Assessment of Human Allergic Diseases

Robert G. Hamilton

Human allergic disease comprises a spectrum of immunoglobulin CLINICAL IMPORTANCE OF TOTAL SERUM IGE
E (IgE)–mediated immediate-type hypersensitivity reactions that
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manifest as reactions in skin (urticaria, dermatitis), the respiratory The concentration of IgE in the serum is highly age dependent.
tract (asthma, rhinitis, or sinusitis), eyes (conjunctivitis), the Cord serum IgE concentrations are low, usually <2 kU/L
gastrointestinal (GI) tract (abdominal pain, bloating, vomiting, (<4.88 µg/L; 1 kU = 2.44 µg and 1 IU = 2.44 ng). Serum IgE
diarrhea), and, in their most extreme condition, systemic anaphy- levels progressively increase in healthy children up to the age of
laxis. These reactions are precipitated by exposure of a genetically 10–15 years and gradually decline in an age-dependent manner
predisposed and sensitized (IgE antibody-positive) individual from the second to the eighth decades of life. Infants with atopia
to a variety of environmental substances that are ubiquitous have an earlier and steeper rise in serum IgE levels during their
and usually well tolerated by most healthy individuals. This early years compared with age-matched controls without atopia. 6
chapter reviews the principles and performance characteristics Clinically, a patient’s total serum IgE level should be evaluated
of analytical methods used in the diagnosis and management against reference intervals established with sera from an age-
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of individuals with allergic disease. It examines in vivo and stratified, healthy skin test-negative (nonatopic) population.
in vitro methods for the quantification of total and allergen- Many clinical laboratories define a total serum IgE >100 kU/L
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specific IgE. (240 ng/mL) as a general demarcation into the atopic region.
After age 14 years, serum IgE levels >333 kU/l (>800 µg/L) are
BIOLOGICAL PROPERTIES OF IGE abnormally elevated and strongly associated with atopic disorders,
such as allergic rhinitis, extrinsic or allergic asthma, and atopic
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In 1921, Prausnitz and Küstner (PK) reported that an intradermal dermatitis. Extreme elevations in serum IgE are common in
(ID) injection of serum from an allergic individual into the skin parasitic infections and are necessary for the diagnosis of the
of an unsensitized (nonallergic) individual, followed 24 hours hyper-IgE (Job’s) syndrome. Low total IgE levels <25 kU/L in
later by injection of specific antigen into the same skin site, individuals with asthma suggest that IgE-mediated mechanisms
induced local itching and swelling surrounded by a zone of play an insignificant role in the pathogenesis of their condition.
erythema. This passively transferred allergic reaction, or PK Low total serum IgE levels thus support the diagnosis of nonal-
reaction, reached a maximum within 10 minutes, persisted for lergic (intrinsic) asthma and help exclude allergic bronchopul-
about 20 minutes, and gradually disappeared. The antibody monary aspergillosis. There is extensive overlap between IgE
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mediating this reaction was shown to be thermolabile, losing its levels in atopic and nonatopic populations, which means that
sensitizing activity after heating serum at 56°C for several hours. an elevated serum IgE can be useful in confirming the clinical
In 1967, this antibody was identified as a fifth human immu- diagnosis of allergic respiratory or skin diseases, but a low or
noglobulin isotype and designated as IgE. 2-4 normal value does not eliminate the possibility of an IgE-mediated
Total serum IgE concentrations are the lowest of the five human mechanism. For instance, a group of adults with allergic asthma
immunoglobulin isotypes (0–0.0001 g/L; 0.004% of the total adult had a mean serum IgE level of 1589 ng/mL (range 55–12 750 ng/
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serum immunoglobulin). Approximately 50% of IgE is localized mL). In contrast, approximately 90% of patients with atopic
in the extravascular space. Its short biological half-life of 1–5 dermatitis had elevated total serum IgE levels (mean 978 kU/L;
days in peripheral blood is primarily the result of a relatively high range 1.3–65,208 kU/L). Parasitic infections, selected immuno-
fractional catabolic rate (71% of the intravascular pool catabolized/ deficiency states, cancer (Hodgkin disease, bronchial carcinoma),
day). IgE does not pass the placenta or activate the classical rheumatoid arthritis, liver disease, and atopic dermatitis (eczema)
complement pathway. Its reaginic (mast-cell sensitizing) activity are other disease states that have been associated with a dysregula-
is dependent on its ability to bind to the α chain of the high- tion of total serum IgE levels. The total serum IgE must therefore
affinity IgE Fc-ε receptor (α-FcεRI) that resides on the membrane be interpreted within the relevant clinical context for each patient.
surface of basophils and mast cells. The interaction between IgE Because of the overlap between individuals with atopia
Fc and the α-FcεRI is blocked by the therapeutic subcutaneous and those without, total serum IgE measurements have been
administration of anti-IgE therapeutics, such as omalizumab (a largely replaced in the routine diagnosis of allergic disease by
humanized IgG1-κ anti-IgE Fc), as discussed below. the quantification of allergen-specific IgE antibody. However,

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