Variability of allergens in commercial fish extracts for skin prick testing
Thimo Ruethers
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorAya C. Taki
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorRoni Nugraha
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Department of Aquatic Product Technology, Bogor Agricultural University, Bogor, Jawa Barat, Indonesia
Search for more papers by this authorTrúc T. Cao
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorMartina Koeberl
Technical Development and Innovation Group, National Measurement Institute, Melbourne, Victoria, Australia
Search for more papers by this authorSandip D. Kamath
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorNicholas A. Williamson
Bio21 Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorSean O'Callaghan
Bio21 Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorShuai Nie
Bio21 Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorSam S. Mehr
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Department of Allergy and Immunology, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Department of Allergy and Immunology, Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorDianne E. Campbell
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Department of Allergy and Immunology, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
Search for more papers by this authorCorresponding Author
Andreas L. Lopata
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Correspondence
Andreas L. Lopata; Pharmacy and Medical Research Building, James Cook University, Townsville, QLD, Australia.
Email: [email protected]
Search for more papers by this authorThimo Ruethers
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorAya C. Taki
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorRoni Nugraha
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Department of Aquatic Product Technology, Bogor Agricultural University, Bogor, Jawa Barat, Indonesia
Search for more papers by this authorTrúc T. Cao
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorMartina Koeberl
Technical Development and Innovation Group, National Measurement Institute, Melbourne, Victoria, Australia
Search for more papers by this authorSandip D. Kamath
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Search for more papers by this authorNicholas A. Williamson
Bio21 Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorSean O'Callaghan
Bio21 Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorShuai Nie
Bio21 Mass Spectrometry and Proteomics Facility, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorSam S. Mehr
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Department of Allergy and Immunology, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Department of Allergy and Immunology, Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
Search for more papers by this authorDianne E. Campbell
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Department of Allergy and Immunology, Children's Hospital at Westmead, Sydney, New South Wales, Australia
Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
Search for more papers by this authorCorresponding Author
Andreas L. Lopata
Molecular Allergy Research Laboratory, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, Queensland, Australia
Centre for Food and Allergy Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia
Correspondence
Andreas L. Lopata; Pharmacy and Medical Research Building, James Cook University, Townsville, QLD, Australia.
Email: [email protected]
Search for more papers by this authorAbstract
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.
Graphical Abstract
Commercial skin prick test (SPT) extracts often contain insufficient amounts of important fish allergens, resulting in low IgE reactivity. Collagen, tropomyosin and aldolase A are of under-recognized importance for the diagnosis of fish allergy. Understanding the molecular allergology of SPT allergen extracts is essential for best diagnostics.
CONFLICTS OF INTEREST
The authors declare that they have no conflicts of interest.
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REFERENCES
- 1Sharp MF, Lopata AL. Fish allergy: in review. Clin Rev Allergy Immunol. 2014; 46(3): 258-271.
- 2Moonesinghe H, Mackenzie H, Venter C, et al. Prevalence of fish and shellfish allergy: a systematic review. Ann Allergy Asthma Immunol. 2016; 117(3): 264-272.
- 3Lopata AL, Jeebhay MF. Airborne seafood allergens as a cause of occupational allergy and asthma. Curr Allergy Asthma Rep. 2013; 13(3): 288-297.
- 4Ruethers T, Taki AC, Johnston EB, et al. Seafood allergy: a comprehensive review of fish and shellfish allergens. Mol Immunol 2018; 100: 28-57.
- 5Matricardi P, Kleine-Tebbe J, Hoffmann H, et al. EAACI molecular allergology user's guide. Pediatr Allergy Immunol 2016; 27(S23): 1350-250.
- 6Ruethers T, Raith M, Sharp M, et al. Characterization of Ras k 1 a novel major allergen in Indian mackerel and identification of parvalbumin as the major fish allergen in 33 Asia-Pacific fish species. Clin Exp Allergy 2018; 48(4): 452-463.
- 7Hoffmann A, Jamin A, Foetisch K, et al. Determination of the allergenic activity of birch pollen and apple prick test solutions by measurement of beta-hexosaminidase release from RBL-2H3 cells. Comparison with classical methods in allergen standardization. Allergy. 1999; 54(5): 446-454.
- 8Sander I, Fleischer C, Meurer U, Bruning T, Raulf-Heimsoth M. Allergen content of grass pollen preparations for skin prick testing and sublingual immunotherapy. Allergy 2009; 64(10): 1486-1492.
- 9Kespohl S, Maryska S, Bünger J, et al. How to diagnose mould allergy? Comparison of skin prick tests with specific IgE results. Clin Exp Allergy 2016; 46(7): 981-991.
- 10Kespohl S, Maryska S, Zahradnik E, Sander I, Bruning T, Raulf-Heimsoth M. Biochemical and immunological analysis of mould skin prick test solution: current status of standardization. Clin Exp Allergy 2013; 43(11): 1286-1296.
- 11Sander I, Merget R, Degens PO, Goldscheid N, Bruning T, Raulf-Heimsoth M. Comparison of wheat and rye flour skin prick test solutions for diagnosis of baker's asthma. Allergy 2004; 59(1): 95-98.
- 12van Kampen V, Merget R, Rabstein S, et al. Comparison of wheat and rye flour solutions for skin prick testing: a multi-centre study (Stad 1). Clin Exp Allergy 2009; 39(12): 1896-1902.
- 13van Kampen V, de Blay F, Folletti I, et al. Evaluation of commercial skin prick test solutions for selected occupational allergens. Allergy 2013; 68(5): 651-658.
- 14Asero R, Scala E, Villalta D, et al. Shrimp allergy: analysis of commercially available extracts for in vivo diagnosis. J Investg Allergol Clin Immunol. 2017; 27(3): 175-182.
- 15Kuehn A, Scheuermann T, Hilger C, Hentges F. Important variations in parvalbumin content in common fish species: a factor possibly contributing to variable allergenicity. Int Arch Allergy Immunol 2010; 153(4): 359-366.
- 16Stephen J, Sharp M, Ruethers T, Taki A, Campbell D, Lopata AL. Allergenicity of bony and cartilaginous fish–molecular and immunological properties. Clin Exp Allergy 2017; 47(3): 300-312.
- 17Liu R, Holck AL, Yang E, Liu C, Xue W. Tropomyosin from tilapia (Oreochromis mossambicus) as an allergen. Clin Exp Allergy 2013; 43(3): 365-377.
- 18Gonzalez-Fernandez J, Veleiro B, Daschner A, Cuellar C. Are fish tropomyosins allergens? Ann Allergy Asthma Immunol 2016; 116(1): 74-76.
- 19Kuehn A, Hilger C, Lehners-Weber C, et al. Identification of enolases and aldolases as important fish allergens in cod, salmon and tuna: component resolved diagnosis using parvalbumin and the new allergens. Clin Exp Allergy 2013; 43(7): 811-822.
- 20Shimizu Y, Nakamura A, Kishimura H, Hara A, Watanabe K, Saeki H. Major allergen and its IgE cross-reactivity among salmonid fish roe allergy. J Agric Food Chem 2009; 57(6): 2314-2319.
- 21Kobayashi Y, Akiyama H, Huge J, et al. Fish collagen is an important panallergen in the Japanese population. Allergy 2016; 71(5): 720-723.
- 22Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-685.
- 23Sharp MF, Stephen JN, Kraft L, Weiss T, Kamath SD, Lopata AL. Immunological cross-reactivity between four distant parvalbumins-Impact on allergen detection and diagnostics. Mol Immunol 2015; 63(2): 437-448.
- 24Kamath SD, Thomassen MR, Saptarshi SR, et al. Molecular and immunological approaches in quantifying the air-borne food allergen tropomyosin in crab processing facilities. Int J Hyg Environ Health 2014; 217(7): 740-750.
- 25Nugraha R, Kamath SD, Johnston E, et al. Rapid and comprehensive discovery of unreported shellfish allergens using large-scale transcriptomic and proteomic resources. J Allergy Clin Immunol. 2018; 141(4): 1501-1504.
- 26Tyanova S, Temu T, Sinitcyn P, et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat Methods 2016; 13(9): 731-740.
- 27Kamath SD, Rahman AM, Voskamp A, et al. Effect of heat processing on antibody reactivity to allergen variants and fragments of black tiger prawn: a comprehensive allergenomic approach. Mol Nutr Food Res 2014; 58(5): 1144-1155.
- 28Raith M, Klug C, Sesztak-Greinecker G, et al. Unusual sensitization to parvalbumins from certain fish species. Ann Allergy Asthma Immunol 2014; 113(5): 571-572.
- 29Kuehn A, Hutt-Kempf E, Hilger C, Hentges F. Clinical monosensitivity to salmonid fish linked to specific IgE-epitopes on salmon and trout beta-parvalbumins. Allergy 2011; 66(2): 299-301.
- 30Ebo DG, Kuehn A, Bridts CH, Hilger C, Hentges F, Stevens WJ. Monosensitivity to Pangasius and Tilapia caused by allergens other than parvalbumin. J Investig Allergol Clin Immunol. 2010; 20(1): 84-88.
- 31Liang J, Tan CC, Taylor SL, Baumert JL, Lopata AL, Lee NA. Quantitative analysis of species specificity of two anti-parvalbumin antibodies for detecting southern hemisphere fish species demonstrating strong phylogenetic association. Food Chem. 2017; 237: 588-596.
- 32Beale JE, Jeebhay MF, Lopata AL. Characterisation of purified parvalbumin from five fish species and nucleotide sequencing of this major allergen from Pacific pilchard Sardinops sagax. Mol Immunol. 2009; 46(15): 2985-2993.
- 33Griesmeier U, Vazquez-Cortes S, Bublin M, et al. Expression levels of parvalbumins determine allergenicity of fish species. Allergy. 2010; 65(2): 191-198.
- 34Chikazawa S, Hashimoto T, Kobayashi Y, Satoh T. Fish-collagen allergy: a pitfall of the prick-to-prick test with raw fish. Br J Dermatol. 2015; 173(5): 1330-1331.
- 35Sakaguchi M, Toda M, Ebihara T, et al. IgE antibody to fish gelatin (type I collagen) in patients with fish allergy. J Allergy Clin Immunol. 2000; 106(3): 579-584.