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Component-Resolved and Complementary Tests in the Diagnosis of Occupational Allergy: Advantages and Limitations

  • Occupational Allergy (S Quirce and J Sastre, Section Editors)
  • Published:
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Opinion Statement

Enhancing the repertoire of in vitro methods together with the development of recombinant technology in the field of allergy diagnosis brought tremendous advances in understanding allergens, allergic reactions, and patients’ care. This review is focusing not only on component-resolved diagnosis with occupational allergens, complementary methods, their advantages to improve the in vitro diagnosis for occupational allergy but also their limitations. Up to now, the number of occupational asthma sensitizers characterized on the molecular level and their availability for routine diagnosis is very low. One exception, however, is Hevea brasiliensis latex as an important occupational allergen source. H. brasiliensis latex is an excellent model for the useful application of recombinant single allergens for improvement of routine diagnostics. Despite the many efforts and excellent research in the field of baker’s asthma to characterize the occupationally relevant allergens the results are highly diverse. No major allergen can be identified and the IgE-sensitization profile of each baker showed great inter-individual variation. Therefore, for routine diagnosis of baker’s asthma, the assessment of allergen-specific IgE with the whole wheat (and/or rye) flour extract is still recommended. Unfortunately, no wheat allergens relevant for baker’s asthma are commercially available, although they might help to discriminate between wheat-induced food allergy, grass pollen allergy, and baker’s asthma. In particular cases with discrepancy between different diagnostic tests, the determination of basophil activation test is a recommended option. Flow cytometry determination of CD63 or CD203c on basophils induced by stimulation with the relevant allergen is a good clinically validated test and also useful for the diagnosis of occupational allergy. It is still necessary to increase the knowledge of occupational allergen molecules and include standardized tools into routine diagnostic. For the future, combination of new diagnostic tools and biomarkers, platforms, and complementary methods in occupational allergy and asthma diagnosis is a promising option. In addition, integration of these possibilities in workplace-related allergy and asthma studies is helpful to understand the complex interaction between work-related exposure, individual susceptibility and health outcome.

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Abbreviations

BAT:

Basophil activation test

CAST:

Cellular antigen stimulation assay

CCD:

Cross-reactive carbohydrate determinant

CRD:

Component-resolved diagnosis

Hev b:

Hevea brasiliensis

Tri a:

Triticum aestivum

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of special interest •• Of outstanding interest

  1. Jeebhay MF, Quirce S. Occupational asthma in the developing and industrialised world: a review. Int J Tuberc Lung Dis. 2007;11:122–33.

    CAS  PubMed  Google Scholar 

  2. Moscato G, Pala G, Barnig C, De Blay F, Del Giacco SR, Folletti I, et al. EAACI consensus statement for investigation of work-related asthma in non-specialized centres. Allergy. 2012;67:491–501.

    Article  CAS  PubMed  Google Scholar 

  3. •• Quirce S, Campo P, Domingues-Ortega, Fernández-Nieto M, Gómez-Torrijo E, Martínez-Arcediano A, et al. New developments in work-related asthma. Expert Rev Clin Immunol. 2017;13:271–281.This state-of-the-art review provides an update on the definitions and the clinical features of the different work-related asthma subtypes as well as new insights into their etiology and the pathophysiological mechanisms involved.

  4. Cartier A. New causes of immunologic occupational asthma 2012-2014. Curr Opin Allergy Clin Immunol. 2015;15:117–23.

    Article  CAS  PubMed  Google Scholar 

  5. •• Quirce S. IgE antibodies in occupational asthma: are they causative or an associated phenomenon? Curr Opin Allergy Clin Immunol. 2014;14:100–5.Critical and comprehensive review about the relevance of IgE determinations in the occupational asthma.

    Article  CAS  PubMed  Google Scholar 

  6. Quirce S, Bernstein JA. Old and new causes of occupational asthma. Immunol Allergy Clin N Am. 2011;31:677–98.

    Article  Google Scholar 

  7. •• Vandenplas O, Suojalehto H, Cullinan P. Diagnosing occupational asthma. Clin Exp Allergy. 2017;47:6–18.State-of-the-art review which provides a technical dossier of the diagnostic value of the available methods on diagnosing occupational asthma.

  8. Renz H, Biedermann T, Bufe A, Eberlein B, Jappe U, Ollert M, et al. In-vitro-Allergiediagnostik. Allergo J. 2010;19:110–28.

    Article  Google Scholar 

  9. van Kampen V, de Blay F, Folletti I, Kobierski P, Moscato G, Olivieri M, et al. Evaluation of commercial skin prick test solutions for selected occupational allergens. Allergy. 2013;68:651–8.

    Article  PubMed  Google Scholar 

  10. van Kampen V, de Blay F, Folletti I, Kobierski P, Moscato G, Olivieri M. EAACI position paper: skin prick testing in the diagnosis of occupational type I allergies. Allergy. 2013;68:580–4.

    Article  PubMed  Google Scholar 

  11. Raulf M. Werkzeuge für die Diagnostik einer berufsbedingten Typ I-Allergie. Atemwegs- und Lungenkrankheiten. 2014;40:128–37.

    Article  Google Scholar 

  12. van Kampen V, Rabstein S, Sander I, Merget R, Brüning T, Broding HC, et al. Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers. Allergy. 2008;63:897–902.

    Article  PubMed  Google Scholar 

  13. • Matricardi PM, Kleine-Tebbe J. Molecular allergology between precision medicine and the choosing wisely initiative. Clin Exp Allergy. 2016;46:664–7.The editorial discusses the findings of a paper, additionally includes some general aspects about the value and the interpretation of results obtained with CRD.

    Article  CAS  PubMed  Google Scholar 

  14. •• Raulf M. Allergen component analysis as a tool in the diagnosis of occupational allergy. Curr Opin Allergy Clin Immunol. 2016;16:93–100.An insightful reappraisal of the state-of-the- art on component-resolved diagnosis in the occupational field.

    Article  CAS  PubMed  Google Scholar 

  15. •• Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, Valenta R, Hilger C, Hofmaier S, et al. EAACI molecular allergology user’s guide. Pediatr Allergy Immunol. 2016;23:1–250.Outstanding overview and highly recommended user’s guide for all those health professionals who are dealing everyday with allergic patients. It is a straightforward guide on molecular allergology describing the relevant molecules, the clinical benefits of testing components as well as how to interpret the results. Should be used as an essential daily pocket guide for allergists working in the allergology field.

    Article  Google Scholar 

  16. Raulf-Heimsoth M, Rihs HP, Rozynek P, Cremer R, Gaspar Â, Pires G, et al. Quantitative analysis of immunoglobulin E reactivity profiles in patients allergic or sensitized to natural rubber latex (Hevea brasiliensis). Clin Exp Allergy. 2007;37:1657–67.

    Article  CAS  PubMed  Google Scholar 

  17. Ebo DG, Hagendorens MM, De Knop KJ, Verweij MM, Bridts CH, De Clerck LS, Stevens WJ. Component-resolved diagnosis from latex allergy by microarray. Clin Exp Allergy. 2010;40:348–58.

    Article  CAS  PubMed  Google Scholar 

  18. • Seyfarth F, Schliemann S, Wiegand C, Hipler UC, Elsner P. Diagnostic value of the ISAC® allergy chip in detecting latex sensitizations. Int Arch Occup Environ Health. 2014;87:775–81.Study comparing the ISAC® chip and the conventional ImmunoCAP k 82 in the context of clinical relevant latex allergy.

    Article  CAS  PubMed  Google Scholar 

  19. Chełmińska M, Specjalski K, Różyło A, Kołakowska A, Jassem E. Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test. Postepy Dermatol Alergol. 2016;33:120–7.

    PubMed  PubMed Central  Google Scholar 

  20. Kespohl S, Schlünssen V, Jacobsen G, Schaumburg I, Maryska S, Meurer U, et al. Impact of cross-reactive carbohydrate determinants on wood dust sensitization. Clin Exp Allergy. 2010;40:1099–106.

    Article  CAS  PubMed  Google Scholar 

  21. Caballero ML, Quirce S. Identification and practical management of latex allergy in occupational settings. Expert Rev Clin Immunol. 2015;11:977–92.

    Article  CAS  PubMed  Google Scholar 

  22. •• Vandenplas O, Froidure A, Meurer U, Rihs HP, Rifflart C, Soetaert S, et al. The role of allergen components for the diagnosis of latex-induced occupational asthma. Allergy. 2016;71:840–9.This study shows that the most reliable tool for predicting bronchial reactivity to natural rubber latex is the combination of the levels of specific IgE antibodies against the recombinant allergen components Hev b 5 with Hev b 6.01 or 6.02.

    Article  CAS  PubMed  Google Scholar 

  23. •• Quirce S, Boyano-Martínez T, Díaz-Perales A. Clinical presentation, allergens, and management of wheat allergy. Expert Rev Clin Immunol. 2016;12:563–72.Overview about the various faces of wheat allergy by exposure through ingestion, inhalation or skin/mucosal contact.

    Article  CAS  PubMed  Google Scholar 

  24. Sander I, Rozynek P, Rihs HP, van Kampen V, Chew FT, Lee WS, et al. Multiple wheat flour allergens and cross-reactive carbohydrate determinants bind IgE in baker’s asthma. Allergy. 2011;66:1208–15.

    Article  CAS  PubMed  Google Scholar 

  25. Olivieri M, Biscardo CA, Palazzo P, Pahr S, Malerba G, Ferrara R, et al. Wheat IgE profiling and wheat IgE levels in bakers with allergic occupational phenotypes. Occup Environ Med. 2013;70:617–22.

    Article  CAS  PubMed  Google Scholar 

  26. Gómez-Casado C, Garrido-Arandia M, Pereira C, Catarino M, Parro V, Armentia A, et al. Component-resolved diagnosis of wheat flour allergy in baker’s asthma. J Allergy Clin Immunol. 2014;134:480–3.

    Article  PubMed  Google Scholar 

  27. Baar A, Pahr S, Constantin C, Giavi S, Manoussaki A, Papadopoulos NG, et al. Specific IgE reactivity to Tri a 36 in children with wheat food allergy. J Allergy Clin Immunol. 2014;133:585–7.

    Article  CAS  PubMed  Google Scholar 

  28. Takahashi H, Matsuo H, Chinuki Y, Kohno K, Tanaka A, Maruyama N, et al. Recombinant high molecular weight-glutenin subunit-specific IgE detection is useful in identifying wheat-dependent exercise-induced anaphylaxis complementary to recombinant omega-5 gliadin-specific IgE test. Clin Exp Allergy. 2012;42:1293–8.

    Article  CAS  PubMed  Google Scholar 

  29. Altenbach SB, Tanaka CK, Pineau F, Lupi R, Drouet M, Beaudouin E, et al. Assessment of the allergenic potential of transgenic wheat (Triticum aestivum) with reduced levels of ω5-gliadins, the major sensitizing allergen in wheat-dependent exercise-induced anaphylaxis. J Agric Food Chem. 2015;63:9323–32.

    Article  CAS  PubMed  Google Scholar 

  30. •• Sander I, Rihs HP, Doekes G, Quirce S, Krop E, Rozynek P, et al. Component-resolved diagnosis of baker’s allergy based on specific IgE to recombinant wheat flour proteins. J Allergy Clin Immunol. 2015;135:1529–37.Very informative study of CRD in baker’s asthma with evaluation of the diagnostic efficiencies of IgE tests with a comprehensive panel of single allergens and assessing their ability to discriminate between patients with baker’s allergy and control subjects.

    Article  CAS  PubMed  Google Scholar 

  31. • Sander I, Rihs HP, Brüning T, Raulf M. A further wheat allergen for baker's asthma: Tri a 40. J Allergy Clin Immunol. 2016;137:1286.Complementary study to answer the question how important are missing wheat allergens for diagnosis of baker’s asthma.

  32. van Rooy FG, Houba R, Palmen N, Zengeni MM, Sander I, Spithoven J, Rooyackers JM, Heederik DJ. A cross-sectional study among detergent workers exposed to liquid detergent enzymes. Occup Environ Med. 2009;66:759–65.

    Article  PubMed  Google Scholar 

  33. • Stöcker B, Grundmann S, Mosters P, Nitzsche P, Brehler R. Occupational sensitization to lactase in the dietary supplement industry. Arch Environ Occup Health. 2016;71:259–67.Interesting field study concerning the occupational sensitization to the enzyme lactase with implementation of different methods to verify the sensitization.

    Article  PubMed  Google Scholar 

  34. de Weck AL, Sanz ML. Cellular allergen stimulation test (CAST) 2003, a review. J Investig Allergol Clin Immunol. 2004;14:253–73.

    PubMed  Google Scholar 

  35. •• Hoffmann HJ, Santos AF, Mayorga C, Nopp A, Eberlein B, Ferrer M, et al. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease. Allergy. 2015;70:1393–405.EAACI position paper providing an overview of the practical and technical details as well as clinical utility of BAT in diagnosis and management of allergic diseases.

    Article  CAS  PubMed  Google Scholar 

  36. Boumiza R, Monneret G, Forisier MF, Savoye J, Gutowksi MC, Powell WS, et al. Marked improvement of the basophil acitivation test by detectiong CD203c instead of CD63. Clin Exp Allergy. 2003;33:259–65.

    Article  CAS  PubMed  Google Scholar 

  37. Sanz ML, Gamboa PM, Mayorga C. Basophil activation tests in the evaluation of immediate drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2009;9:298–304.

    Article  CAS  PubMed  Google Scholar 

  38. Pala G, Pignatti P, Perfetti L, Caminati M, Gentile E, Moscato G. Usefulness of basophil activation test in diagnosis of occupational nonasthmatic eosinophilic bronchitis. Allergy. 2010;65:927–9.

    Article  CAS  PubMed  Google Scholar 

  39. Palacin A, Varela J, Quirce S, del Pozo V, Tordesillas L, Barranco P, et al. Recombinant lipid transfer protein Tri a 14: a novel heat and proteolytic resistant tool for the diagnosis of baker's asthma. Clin Exp Allergy. 2009;39:1267–76.

  40. •• Siracusa A, Folletti I, Gerth van Wijk R, Jeebhay MF, Moscato G, Quirce S, et al. Occupational anaphylaxis-an EAACI task force consensus statement. Allergy. 2015;70:141–52.State-of-the-art overview of occupational anaphylaxis as a benchmark for future policies.

    Article  CAS  PubMed  Google Scholar 

  41. Quirce S, Fiandor A. How should occupational anaphylaxis be managed? Curr Opin Allergy Clin Immunol. 2016;16:86–92.

    Article  CAS  PubMed  Google Scholar 

  42. Raulf-Heimsoth M, Liebig R, Marczynski B, Borowitzki G, Bernard S, Freundt S, et al. Implementation of non-invasive methods in the diagnosis of diisocyanate-induced asthma. Adv Exp Med Biol. 2013;788:293–300.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Prevention and Occupational Medicine of the German Social accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany

    Monika Raulf PhD

  2. Institut für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung, Institut der Ruhr-Universität Bochum (IPA), Kompetenz-Zentrum Allergologie/Immunologie, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany

    Monika Raulf PhD

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Correspondence to Monika Raulf PhD.

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Conflict of Interest

Dr. Monika Raulf received speaker’s honoraria from Astellas Pharma GmbH, ThermoFisher Scientific and HAL Allergy.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Occupational Allergy

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Raulf, M. Component-Resolved and Complementary Tests in the Diagnosis of Occupational Allergy: Advantages and Limitations. Curr Treat Options Allergy 4, 171–180 (2017). https://doi.org/10.1007/s40521-017-0124-6

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