Abstract
Background: IgE-mediated fish allergy has long been considered
an umbrella term due to the high cross-reactivity of parvalbumin, the
major fish allergen. Yet, clinical tolerance to certain fish highlights
allergenicity differences. In this study, we sought to construct a fish
allergenicity ladder and identify fish parvalbumin epitopes to improve
the diagnosis of fish allergy.
Methods: Reported clinical history and the serum-specific IgE
(sIgE) responses of 200 fish allergic patients were collected and
analyzed, while the relative parvalbumin content in different fish were
measured for the construction of fish allergenicity ladder. Double-blind
placebo-controlled food challenge (DBPCFC) and open challenge against
salmon, grass carp and grouper were performed in 58 selected patients
for validation of the ladder. Epitope mapping was performed by peptide
array against parvalbumins of salmon (both β-1 and β-2), cod, grouper,
and grass carp with sera from fish allergic (n=11), partial fish
tolerant (n=12), and complete fish tolerant (n=5) patients diagnosed
based on oral food challenge outcome.
Results: The distribution pattern of clinical, sIgE and
molecular data and their strong positive correlation led to the
construction of a 4-step fish allergenicity ladder comprising: step 1 of
the least allergenic fishes (tuna, halibut, salmon), steps 2 (cod) and 3
(herring and grouper) of moderately allergenic fishes to step 4 of
highly allergenic fishes (catfish, grass carp and tilapia). Epitope
mapping revealed one epitope from grouper parvalbumin (AA64-78) for
diagnosing general fish allergy and one epitopic region from salmon
parvalbumin (AA19-33) as biomarker of specific fish tolerance. Only
epitope-specific IgE differentiated these patients but not sIgE to fish
extract or parvalbumin.
Conclusion: The fish ladder and epitopes discovery can
precisely differentiate fish-allergic and tolerant subjects and guide
fish reintroduction by stepping up the ladder, which innovate fish
allergy care in the next millennium.