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Background: Major fish allergens, including parvalbumin (PV), are heat stable and can withstand extensive cooking processes. Thus, the management of fish allergy generally relies on complete avoidance. Fish-allergic patients may be advised to consume canned fish, as some fish-allergic individuals have reported tolerance to canned fish. However, the safety of consuming canned fish has not been evaluated with comprehensive immunological and molecular analysis of canned fish products., Methods: We characterized the in vitro immunoreactivity of serum obtained from fish-allergic subjects to canned fish. Seventeen canned fish products (salmon n = 8; tuna n = 7; sardine n = 2) were assessed for the content and integrity of PV using allergen-specific antibodies. Subsequently, the sIgE binding of five selected products was evaluated for individual fish-allergic patients (n = 53). Finally, sIgE-binding proteins were identified by mass spectrometry., Results: The canned fish showed a markedly reduced PV content and binding to PV-specific antibodies compared with conventionally cooked fish. However, PV and other heat-stable fish allergens, including tropomyosin and collagen, still maintained their sIgE-binding capacity. Of 53 patients, 66% showed sIgE binding to canned fish proteins. The canned sardine contained proteins bound to sIgE from 51% of patients, followed by canned salmon (43%-45%) and tuna (8%-17%). PV was the major allergen in canned salmon and sardine. Tropomyosin and/or collagen also showed sIgE binding., Conclusion: We showed that canned fish products may not be safe for all fish-allergic patients. Canned fish products should only be considered into the diet of individuals with fish allergy, after detailed evaluation which may include in vitro diagnostics to various heat-stable fish allergens and food challenge conducted in suitable environments., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Diagnostic tests for fish allergy are hampered by the large number of under-investigated fish species. Four salmon allergens are well-characterized and registered with the WHO/IUIS while no catfish allergens have been described so far. In 2008, freshwater-cultured catfish production surpassed that of salmon, the globally most-cultured marine species. We aimed to identify, quantify, and compare all IgE-binding proteins in salmon and catfish., Methods: Seventy-seven pediatric patients with clinically confirmed fish allergy underwent skin prick tests to salmon and catfish. The allergen repertoire of raw and heated protein extracts was evaluated by immunoblotting using five allergen-specific antibodies and patients' serum followed by mass spectrometric analyses., Results: Raw and heated extracts from catfish displayed a higher frequency of IgE-binding compared to those from salmon (77% vs 70% and 64% vs 53%, respectively). The major fish allergen parvalbumin demonstrated the highest IgE-binding capacity (10%-49%), followed by triosephosphate isomerase (TPI; 19%-34%) in raw and tropomyosin (6%-32%) in heated extracts. Six previously unidentified fish allergens, including TPI, were registered with the WHO/IUIS. Creatine kinase from salmon and catfish was detected by IgE from 14% and 10% of patients, respectively. Catfish L-lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, and glucose-6-phosphate isomerase showed IgE-binding for 6%-13% of patients. In salmon, these proteins could not be separated successfully., Conclusions: We detail the allergen repertoire of two highly farmed fish species. IgE-binding to fish tropomyosins and TPIs was demonstrated for the first time in a large patient cohort. Tropomyosins, in addition to parvalbumins, should be considered for urgently needed improved fish allergy diagnostics., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Tropomyosins are highly conserved proteins, an attribute that forms the molecular basis for their IgE antibody cross-reactivity. Despite sequence similarities, their allergenicity varies greatly between ingested and inhaled invertebrate sources. In this study, we investigated the relationship between the structural stability of different tropomyosins, their endolysosomal degradation patterns, and T-cell reactivity., Methods: We investigated the differences between four tropomyosins-the major shrimp allergen Pen m 1 and the minor allergens Der p 10 (dust mite), Bla g 7 (cockroach), and Ani s 3 (fish parasite)-in terms of IgE binding, structural stability, endolysosomal degradation and subsequent peptide generation, and T-cell cross-reactivity in a BALB/c murine model., Results: Tropomyosins displayed different melting temperatures, which did not correlate with amino acid sequence similarities. Endolysosomal degradation experiments demonstrated differential proteolytic digestion, as a function of thermal stability, generating different peptide repertoires. Pen m 1 (T m 42°C) and Der p 10 (T m 44°C) elicited similar patterns of endolysosomal degradation, but not Bla g 7 (T m 63°C) or Ani s 3 (T m 33°C). Pen m 1-specific T-cell clones, with specificity for regions highly conserved in all four tropomyosins, proliferated weakly to Der p 10, but did not proliferate to Bla g 7 and Ani s 3, indicating lack of T-cell epitope cross-reactivity., Conclusions: Tropomyosin T-cell cross-reactivity, unlike IgE cross-reactivity, is dependent on structural stability rather than amino acid sequence similarity. These findings contribute to our understanding of cross-sensitization among different invertebrates and design of suitable T-cell peptide-based immunotherapies for shrimp and related allergies., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Occupational exposure to foods is responsible for up to 25% of cases of occupational asthma and rhinitis. Animal and vegetable high-molecular-weight proteins present in aerosolized foods during food processing, additives, preservatives, antioxidants, and food contaminants are the main inhalant allergen sources. Most agents typically cause IgE-mediated allergic reactions, causing a distinct form of food allergy (Class 3 food allergy). The allergenicity of a food protein, allergen exposure levels, and atopy are important risk factors. Diagnosis relies on a thorough medical and occupational history, functional assessment, assessment of sensitization, including component-resolved diagnostics where appropriate, and in selected cases specific inhalation tests. Exposure assessment, including allergen determination, is a cornerstone for establishing preventive measures. Management includes allergen exposure avoidance or reduction (second best option), pharmacological treatment, assessment of impairment, and worker's compensation. Further studies are needed to identify and characterize major food allergens and define occupational exposure limits, evaluate the relative contribution of respiratory versus cutaneous sensitization to food antigens, evaluate the role of raw versus cooked food in influencing risk, and define the absolute or relative contraindication of patients with ingestion-related food allergy, pollinosis, or oral allergy syndrome continuing to work with exposure to aerosolized food allergens., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Commercial allergen extracts for allergy skin prick testing (SPT) are widely used for diagnosing fish allergy. However, there is currently no regulatory requirement for standardization of protein and allergen content, potentially impacting the diagnostic reliability of SPTs. We therefore sought to analyse commercial fish extracts for the presence and concentration of fish proteins and in vitro IgE reactivity using serum from fish-allergic patients., Methods: Twenty-six commercial fish extracts from five different manufacturers were examined. The protein concentrations were determined, protein compositions analysed by mass spectrometry, followed by SDS-PAGE and subsequent immunoblotting with antibodies detecting 4 fish allergens (parvalbumin, tropomyosin, aldolase and collagen). IgE-reactive proteins were identified using serum from 16 children with confirmed IgE-mediated fish allergy, with focus on cod, tuna and salmon extracts., Results: The total protein, allergen concentration and IgE reactivity of the commercial extracts varied over 10-fold between different manufacturers and fish species. The major fish allergen parvalbumin was not detected by immunoblotting in 6/26 extracts. In 7/12 extracts, five known fish allergens were detected by mass spectrometry. For cod and tuna, almost 70% of patients demonstrated the strongest IgE reactivity to collagen, tropomyosin, aldolase A or β-enolase but not parvalbumin., Conclusions: Commercial fish extracts often contain insufficient amounts of important allergens including parvalbumin and collagen, resulting in low IgE reactivity. A comprehensive proteomic approach for the evaluation of SPT extracts for their utility in allergy diagnostics is presented. There is an urgent need for standardized allergen extracts, which will improve the diagnosis and management of fish allergy., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Hyper-IgE syndromes (HIES) are a clinically overlapping, heterogeneous group of inborn errors of immunity characterized by elevated serum IgE level, eosinophilia, atopy, and immune dysregulation. Deficiency of DOCK8 protein is potentially a life-threatening autosomal recessive HIES and only curable with bone marrow transplantation. Hence, the diagnosis of DOCK8 deficiency is critical and should be sought at an early stage to initiate definitive therapy., Methods: Serum samples from patients with DOCK8 deficiency and atopic dermatitis were profiled on a cytokine/chemokine panel for potential differential expression., Results: CXCL10 and TNF-A were upregulated in DOCK8 patients when compared to AD, possibly contributing toward increased susceptibility to infections and cancer. In contrast, epidermal growth factor (EGF) was significantly downregulated in a subgroup of DOCK8-deficient and AD patients, while IL-31 expression was comparable between both DOCK8-deficient and AD cohorts, possibly contributing toward pruritus seen in both groups., Conclusion: This comprehensive cytokine profile in HIES patients reveals distinctive biomarkers that differentiate between the DOCK8-deficient and AD patients. The unique expression profile of various inflammatory cytokines in patients with DOCK8 deficiency vs atopic dermatitis likely reflects disease-specific perturbations in multiple cellular processes and pathways leading to a predisposition to infections and allergies seen in these patients. These data agree with the role for EGF replacement therapy in EGF-deficient individuals with AD as well as DOCK8 deficiency through a potential shared pathway. In addition, these novel biomarkers may be potentially useful in distinguishing DOCK8 deficiency from AD allowing early-targeted treatment options., (© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood-processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease., Objective: To investigate the roles of interleukin (IL)-4, IL-13 and the IL-4Ralpha in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins., Methods: BALB/c wild-type (WT) mice and mice deficient in IL-4, IL-13 or IL-4 and IL-13, as well as mice with cell-specific impairment of IL-4Ralpha expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization., Results: In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of T(H)2 cytokines, antigen-specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL-13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL-4 only, or deficient in IL-4 and IL-13 concurrently, as well as in mice deficient in IL-4Ralpha or with impaired IL-4Ralpha expression on CD4(+) T cells., Conclusions: Interleukin-13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL-4 drives systemic sensitization and resultant anaphylactic shock.

Background: Recent reports of fatal asthma cases associated with swarms of locusts affecting African countries have highlighted the importance of this insect in causing asthma morbidity and mortality. However, only limited information is available about the allergic health outcomes such as asthma and its determinants in exposed individuals. In this study, workers exposed to the African migratory locust Locusta migratoria were evaluated for allergic health outcomes as well as the nature of the offending allergens., Methods: Ten scientists and technicians exposed to locusts in a laboratory were investigated for locust-related allergy using questionnaires and immunological tests. The presence of allergy was determined by quantification of specific IgE and IgG to L. migratoria using the UniCAP system and via skin-prick testing (SPT). The allergens were characterized by Western blot and ImmunoCAP inhibition assays., Results: Six of the 10 workers experienced symptoms ranging from urticaria and rhinoconjuctivitis to asthma. Seven individuals demonstrated sensitivity on SPT and five had specific IgE antibodies to L. migratoria. Significant cross-reactivity was demonstrated for allergens in the locust faeces, body and wings but not to cockroach allergens. Novel allergens with molecular weights of approximately 70 kDa were identified in locust wings, which are distinctly different from other known allergen sources from locusts., Conclusion: Exposure to L. migratoria allergens is a potential sensitizer in exposed individuals. Raised levels of locust-specific IgE can be readily quantified. The wings of this insect species have been identified as a novel allergen source.