Page 1330 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 95 Assessment of Human Allergic Diseases 1291

Polistes wasp phospholipase A1/B (Ves g 1; Pol a 1) and Antigen preimmunotherapy baseline levels after 2 years of immunotherapy
5 (Ves g 5; Pol a 5) frequently produces IgE antibody cross- discontinuation, overall functional inhibitory activity, as measured
reactivity. Sera from 305 patients with Hymenoptera venom allergy by an IgE-dependent facilitated allergen binding assay, appears
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with >2 ng/mL of IgE antibody to YJV and PWV were evaluated to be maintained. For patients with Hymenoptera venom allergy,
in the IgE antibody inhibition assay to document its clinical specific IgG antibody measurements have been used as an indica-
utility. The diagnostic question for these patients is whether tor of effective immunotherapy. Quantitative venom-specific IgG
PWV should be included in the venom immunotherapy together antibody levels may be useful in individualizing the dose and
with yellow jacket or mixed vespid venom. Using this procedure, frequency of injections while maximizing the protective effects.
the venom-specific IgE antibody inhibition assay identified However, their clinical utility may be restricted to the first 4
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one-third (36.4%) of subjects with a primary YJV sensitivity years of venom immunotherapy. In contrast, the presence or
who were candidates for exclusion of PWV from their immu- levels of IgG antibodies specific for food antigens have shown
notherapy regimen because their IgE anti-PWV was >95% no correlation with the results of positive DBPCFCs, and they
cross-inhibitable with soluble YJV. 57 are not indicated in the diagnostic workup of a patient with
More recently, molecular venom allergens may be particularly suspected food allergy. 34
useful in clarifying whether patients with venom allergies with
IgE antibody positivity for two or more distinct venoms (YJV,
HBV, and/or PWV) reflects true multiple venom sensitization ClInICal PEarlS
or whether the observed multiple positivity results from either Immunoglobulin G (IgG) Antibody Measurements
clinically irrelevant cross-reactive carbohydrate-specific IgE
antibodies or common protein epitopes of homologous venom • Clinically successful aeroallergen immunotherapy is almost always
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antigens. The important carbohydrate cross-reactive determi- accompanied by high serum levels of allergen-specific IgG (predomi-
nantly of the IgG1 and IgG4 subclasses).
nants (CCD) in insect venoms involves an α1,3-linked fucose • Quantitative venom-specific IgG antibody levels can be of value in
residue that is attached to the innermost N-acetylglucosamine individualizing venom doses and frequencies for patients on venom
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carbohydrate on venom proteins. For YJV and HBV, the known immunotherapy for up to 4 years.
cross-reactive proteins include hyaluronidase (Api m 2, Ves v 2), • Food-specific IgG and IgG4 assay results do not correlate with the
dipeptidyl peptidase (Api m 5, Ves v 3), and vitellogenin (Api results of double-blind placebo-controlled food challenges and are not
m 12, Ves v 6). IgE antibody cross-reactivity between YJV and clinically indicated.
PWV is independent of CCD and can occur as a result of common
epitopes on homologous antigens: Antigen 5 (Ves v 5, Pol d 5)
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and phospholipase A 1 (Ves v 1 and Pol d 1). Specific IgE Mast-Cell Tryptase
antibody measurements against rVes v 5 and rPol d 5 alone were Mast cells have been identified in skin, respiratory, and digestive
able to aid in differentiating sensitivity against Vespula and Polistes tract connective tissues and distinguished on the basis of the
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venoms in some patients. However, Savi et al. concluded that neutral proteases present in their secretory granules. One group
the venom competitive inhibition analysis remains the optimal contains only tryptase, whereas the other contains both tryptase
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serological test at present for differentiating between true and and chymase. Mast-cell tryptase (MW 134 kDa) is a serine
cross-reactivity–related dual Vespula and Polistes venom sensitiza- esterase with four subunits, each having an enzymatically active
tion. Moreover, when rPol d 1 becomes available for testing in site. A resting mast cell contains 10–35 picograms (pg) of tryptase
parallel with currently available Ves v 1, Ves v 5, and Pol d 5, the that is stored attached to heparin. When dissociated from heparin,
effectiveness of molecular allergen based differentiation of dual it rapidly degrades into its monomers and loses enzymatic activity.
Vespula and Polistes venom sensitization will need to be As basophils have ~500-fold less tryptase compared with mast
reassessed. cells, elevated tryptase levels in serum are considered a relatively
specific indicator of mast-cell involvement in a clinical reaction.
ClInICal PEarlS Unstimulated tissue mast cells continually secrete immature
Clinical Utility of Immunoglobulin E (IgE) Anti- protryptase into the tissue, and it diffuses into the circulation
Hymenoptera Venom Inhibition Test to provide a measure of total mast-cell number. α-Protryptase
and β-protryptase represent the bulk of the immature tryptase
• Useful in identifying venom cross-reactive IgE antibodies and selecting in nonanaphylactic sera. α-Protryptase remains enzymatically
appropriate venoms for immunotherapy. inactive, whereas some of β-protryptase is autoprocessed from
• One-third of venom-allergic patients with concomitant yellow jacket the proform within the mast cell into the mature enzyme
venom (YJV) and Polistes wasp venom (PWV) sensitivity can be treated by a dipeptidase where it is stored in granules. Only upon
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with YJV alone or mixed vespid venoms, owing to >95% cross-reactive
IgE anti-PWV with soluble YJV. activation of mast cells are both the pro and mature forms of
tryptase secreted in parallel with prestored histamine and newly
generated vasoactive mediators. Total tryptase in serum from
Allergen-Specific IgG healthy humans ranges from 1 to 11.4 µg/L (average 3–5 µg/L).
Allergen immunotherapy is known to enhance the production Mature tryptase is normally undetectable (<1 µg/L) in serum from
of specific IgG “blocking” antibodies. 62,63 Quantitative measure- healthy individuals who have no history of anaphylaxis during the
ments of allergen-specific total IgG or IgG subclass antibodies preceding hours. A noncompetitive two-site fluorescent enzyme
in studies of allergic rhinitis have not generally correlated with immunoassay (Phadia, ImmunoCAP) is available to measure total
the control of clinical symptoms in individual patients. However, tryptase in serum. Elevated levels of total tryptase (>11.4 µg/L)
clinically successful immunotherapy is almost always accompanied can be detected in serum 1–4 hours after the onset of systemic
by high serum levels of allergen-specific IgG (typically IgG1 and anaphylaxis with hypotension. Baseline levels of >20 µg/L are
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IgG4) blocking antibodies. Interestingly, despite a decrease to detected in most individuals with systemic mastocytosis.