Page 1323 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1284 Part ElEvEn Diagnostic Immunology

quantification of total serum IgE has remained important for when dealing with allergens (e.g., foods, molds) where commercial
computing the therapeutic dose of anti-IgE. Omalizumab is a extracts can be highly variable or labile. 13,16
recombinant, humanized IgG1-κ monoclonal antihuman IgE Fc
drug that specifically binds to the region on the ε heavy chain that CLINICAL HISTORY
interacts with α-FcεR1. 10,11 It is used to treat moderate to severe
persistent allergic asthma and chronic idiopathic urticaria by The diagnosis of human allergic disease is driven principally
blocking IgE binding to the α-FcεR1. The binding of omalizumab by the patient’s clinical history in which objective evidence is
to IgE in vivo reduces both the number of free IgE molecules collected that an allergic reaction has occurred following exposure
able to interact with the α-FcεR1 and the number of α-FcεR1 to a known or suspected allergen source. During the history, a
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receptors on the surface of effector cells. The consequence is a number of factors need to be considered. These include the
reduction in mediator release and allergy symptoms following patient’s symptom characteristics (location, reproducibility,
allergen exposure. 10,11 severity, duration, delay time from appearance following allergen
exposure), atopic factors (personal and family histories, age of
CLINICAL IMPORTANCE OF onset, infantile atopic dermatitis), opportunity for sensitization
ALLERGEN-SPECIFIC IGE (geography, seasons, duration of exposure, prior exposures,
employment, and hobbies), specificity of allergen triggers, and
In contrast to total serum IgE, the presence of allergen-specific comorbidities (e.g., nasal polyps, recurrent sinusitis, chronic
IgE antibody on the surface of circulating basophils or skin mast obstructive pulmonary disease [COPD]). From the history, an
cells or in the serum is highly predictive of an individual’s a priori or pretest probability or likelihood of allergic disease is
propensity to exhibit an allergic response following reexposure derived, and this determines whether or not confirmatory IgE
to that allergen. Before its identification as a novel immuno- antibody testing for sensitization is warranted.
globulin, IgE was only detectable with in vivo bioassays (skin
test, bronchial or nasal provocation tests). Purification of IgE DIAGNOSTIC METHODS
myeloma protein and the subsequent production of antisera
specific for IgE led to the development of the first in vitro assay A combination of in vivo provocation and in vitro laboratory
(radioallergosorbent test [RAST]) for the detection of allergen- tests may be used to confirm sensitization and provide support
specific IgE antibody in serum. 4,12,13 Since then, nonisotopic for the clinical diagnosis of allergic disease. The actual tests
autoanalyzer variants based on the original noncompetitive selected depend on the nature of the disease process (e.g., allergic
cellulose paper disc solid-phase RAST design have been widely asthma, urticaria/angioedema, rhinitis/sinusitis, or anaphylaxis)
used in clinical immunology laboratories throughout the and the suspected allergen triggers (e.g., aeroallergens, venoms,
world. 13,14 These assays, discussed below, involve an immobilized drugs, foods) under investigation. In making a decision about
allergen containing reagent that binds allergen-specific antibody which diagnostic test to perform, clinicians start by searching
from human serum and an enzyme conjugated anti-IgE the for information on the diagnostic sensitivity and specificity of
detects bound IgE antibody. each confirmatory test. The true diagnostic sensitivity or ability
Historical studies have compared the diagnostic performance of each test to detect IgE antibody in the presence of allergic
(sensitivity and specificity) of in vivo and the in vitro assays in disease and diagnostic specificity or ability of the test to not detect
the diagnosis of human allergic disease. These intermethod IgE antibody in health (absence of allergic disease) are difficult
comparisons have shown that the presence of IgE antibody as to determine definitively. Not only are there a myriad of assay
measured by serological immunoassay methods usually agrees methods, diverse techniques (e.g., skin testing), reagents (extracts
well with the presence of IgE detected in leukocyte and mast-cell and molecules) and grading, interpolation, and interpretation
histamine release assays, and provocation tests, such as the skin methods, but most importantly, there is a general absence of
test, food challenge, and inhalation provocation test. 15,16 However, gold standard methods for defining the presence of allergic disease.
these early studies emphasize that the presence of IgE antibody For this reason, results of the confirmatory tests need to be
as detected either in vivo or in vitro is at best a confirmatory viewed as additional risk factors and tests for sensitization, rather
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measurement for sensitization. IgE antibody is necessary but than definitive indicators of disease. In the end, the choice of
not sufficient for induction of an allergic symptom. It is considered the confirmatory test is a matter of clinical judgment.
an important risk factor in the diagnosis of allergic disease that
supports a patient’s medical, family, and environmental histories INITIAL CLINICAL LABORATORY TESTS
of a temporal association between allergic symptoms and allergen
exposure. The clinical importance of differences in diagnostic Following the collection of a medical history and performance
sensitivity between skin test and serological detection of IgE of a physical examination, the patient who is suspected of having
antibody may be less important for patients with allergies to allergic disease may undergo several preliminary blood tests. A
inhaled (pollen, dust mite, and epidermal) allergens than in complete blood count (CBC), and/or a total blood eosinophil
those facing life-threatening anaphylactic reactions caused by count, if performed, should be obtained before any systemic
Hymenoptera stings and certain drugs. In these latter cases, skin corticosteroids or epinephrine is administered. A normal whole
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tests are preferable to in vitro immunoassay analyses for the blood eosinophil level ranges from 0 to 500 cells/mm . Children
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detection of allergen-specific IgE antibodies. 16,18 Immunoassays generally have higher normal levels (mean 240 cells/mm 95%
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of IgE antibody in serum can, however, be helpful in cases where confidence interval [CI] = 0–740 cells/mm ), with peak levels
the patient has taken antihistamines, β-receptor stimulants, or occurring at 4–8 years of age. Most clinical laboratories consider
high-dose steroids, which can reduce the in vivo provocation a differential white blood cell (WBC) count with an eosinophil
test’s measured response in children, pregnant women, and older proportion >5–10% of the total WBC count to be abnormal.
patients, in whom skin testing may not be well tolerated and Blood, sputum, and nasal secretion eosinophilia is characteristic