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.

Background The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern towards the identified allergens in fish allergic subjects from two distinct populations in Asia. Methods One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients’ sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80°C were evaluated by SDS-PAGE and mass spectrometry. Results Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. Conclusions Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients’ allergic manifestations.

Background: Anaphylaxis is a significant health burden in most Western countries but there is little published data on the incidence and pattern of anaphylaxis in Asia. We aim to determine the incidence rate and pattern of anaphylaxis over the past decade among the paediatric population in Hong Kong. Methods: Medical records of patients presenting with allergy-related symptoms during the period 2010 to 2019 were examined. Paediatric patients aged below 18 years who fulfilled the diagnostic criteria for anaphylaxis laid out by the NIAID/FAAN were analysed. Incidence rates were calculated using population statistics as the denominator. All information pertaining to the anaphylaxis events and patients’ characteristics were retrieved using standardized data collection forms. Results: The overall 10-year estimated incidence of anaphylaxis was 7.70 per 100,000 person-years, with a rising trend of anaphylaxis incidence across time. Food-induced anaphylaxis accounted for the majority of hospital presentation, of which peanut and shellfish were the top food triggers in our population. Comorbid asthma and young age were risk factors associated with wheeze at presentation. Misdiagnosis of anaphylaxis occurred in up to half the anaphylaxis cases and adrenaline was only utilised in 45% of cases. Conclusions: An increasing trend of anaphylaxis incidence over the past decade is evident in Hong Kong children, with a discrepantly low accuracy in diagnosis and suboptimal management of anaphylaxis. There is a pressing need to heighten public and physicians’ awareness of the distinctive features of anaphylaxis in the paediatric age group.

Background: Anaphylaxis has been increasing in developed countries but there is very little published data on the burden of anaphylaxis and the pattern of adrenaline autoinjector (AAI) prescription from Asia. Objectives: We aim to determine the incidence rates of anaphylaxis and prescription rates of AAI over the past decade in Hong Kong. Methods: Using a centralized electronic database of Hong Kong’s sole public-funded healthcare provider, we obtained and analysed all patients between 2009 and 2019 with physician-reported diagnosis of anaphylaxis. Incidence rates were calculated using population statistics as the denominator. Patients’ prescriptions on discharge were collected to determine the AAI prescription rates. Results: The overall 10-year estimated incidence rate of anaphylaxis was 3.57 per 100,000 person-years. An increasing trend over time across both pediatric and adult populations from 2009 to 2019 was found which was more marked among the pediatric population. There was an overall increasing rates of AAI prescription for patients admitted for anaphylaxis, but the overall AAI prescription rate was less than 15% and was significantly less likely to be prescribed for the adult compared to pediatric patients (36.5% vs. 89.4%, p<0.001). Conclusions: An increasing trend of anaphylaxis incidence rates over the past decade is evident in Asian populations, with a discrepantly low rate of AAI prescription, particularly in the adult patients.