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Fish Allergenicity Ladder and Parvalbumin Epitopes for Predicting Clinical Cross-reactivity and Reintroduction
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  • Christine Yee Yan Wai,
  • Nicki Y.H. Leung,
  • Agnes Sze Yin Leung,
  • Man Fung Tang,
  • Asa Marknell-DeWitt,
  • Jaime Rosa Duque,
  • Gilbert Chua,
  • Yat S. Yau,
  • Wai Hung Chan,
  • Po K. Ho,
  • Mike Kwan YW,
  • Qun U. Lee,
  • Joshua S.C. Wong,
  • Ivan C.S. Lam,
  • James W.C.H. Cheng,
  • David C.K. Luk,
  • Zhongyi Liu,
  • Noelle Anne Ngai,
  • Oi M. Chan,
  • Patrick S C Leung,
  • Gary Wong,
  • Ting Fan Leung
Christine Yee Yan Wai
The Chinese University of Hong Kong Department of Paediatrics
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Nicki Y.H. Leung
The Chinese University of Hong Kong Department of Paediatrics
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Agnes Sze Yin Leung
The Chinese University of Hong Kong Department of Paediatrics
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Man Fung Tang
The Chinese University of Hong Kong Department of Paediatrics
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Asa Marknell-DeWitt
Thermo Fisher Scientific ImmunoDiagnostics Division
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Jaime Rosa Duque
The University of Hong Kong Department of Paediatrics and Adolescent Medicine
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Gilbert Chua
The Chinese University of Hong Kong Department of Paediatrics
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Yat S. Yau
Queen Elizabeth Hospital
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Wai Hung Chan
Queen Elizabeth Hospital
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Po K. Ho
Queen Elizabeth Hospital
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Mike Kwan YW
Princess Margaret Hospital and Yan Chai Hospital
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Qun U. Lee
Princess Margaret Hospital and Yan Chai Hospital
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Joshua S.C. Wong
Princess Margaret Hospital and Yan Chai Hospital
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Ivan C.S. Lam
Princess Margaret Hospital and Yan Chai Hospital
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James W.C.H. Cheng
United Christian Hospital
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David C.K. Luk
United Christian Hospital
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Zhongyi Liu
The Chinese University of Hong Kong Department of Paediatrics
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Noelle Anne Ngai
The Chinese University of Hong Kong Department of Paediatrics
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Oi M. Chan
The Chinese University of Hong Kong Department of Paediatrics
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Patrick S C Leung
University of California Davis
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Gary Wong
The Chinese University of Hong Kong Department of Paediatrics
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Ting Fan Leung
The Chinese University of Hong Kong Department of Paediatrics

Corresponding Author:tfleung@cuhk.edu.hk

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Abstract

not-yet-known not-yet-known not-yet-known unknown 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.
19 Aug 2024Submitted to Allergy
20 Aug 2024Submission Checks Completed
20 Aug 2024Assigned to Editor
20 Aug 2024Review(s) Completed, Editorial Evaluation Pending
23 Aug 2024Reviewer(s) Assigned
30 Sep 2024Editorial Decision: Revise Minor