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Current Allergy and Asthma Reports
Published in: Current Allergy and Asthma Reports 9/2015

Open Access 01-09-2015 | Immunologic/Diagnostic Tests in Allergy (M Chapman and A Pomés, Section Editors)

Applications of Molecular Diagnostic Testing in Food Allergy

Authors: Karin Hoffmann-Sommergruber, Sabine Pfeifer, Merima Bublin

Published in: Current Allergy and Asthma Reports | Issue 9/2015

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Abstract

IgE-mediated food allergy is a relevant health problem inducing symptoms ranging from mild local reactions up to severe life-threatening situations. Currently, no immunotherapy is available and avoidance of the incriminating food is the method of choice. Therefore, reliable diagnostic tools to formulate dietary recommendations and to avoid unnecessary exclusion diets for the individual patient are urgently needed. This review provides an update on the current knowledge on food allergens and their application in various diagnostic approaches such as skin prick test, basophil activation test, and serum IgE testing. Furthermore, these new approaches are discussed and compared to conventional extract-based assays and correlated to the gold standard of food allergy diagnosis, the double-blind placebo-controlled food challenge. Finally, the application of food allergens for preventive measurements such as allergen detection assays and the determination of threshold levels for allergen levels are discussed.
Literature
1.
Nwaru BI, Hickstein L, Panesar SS, Roberts G, Muraro A, Sheikh A. Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy. 2014;69(8):992–1007.CrossRefPubMed
2.
Nwaru BI, Hickstein L, Panesar SS, Muraro A, Werfel T, Cardona V, et al. The epidemiology of food allergy in Europe: a systematic review and meta-analysis. Allergy. 2014;69(1):62–75.CrossRefPubMed
3.
Muraro A, Werfel T, Hoffmann-Sommergruber K, Roberts G, Beyer K, Bindslev-Jensen C, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014;69(8):1008–25.CrossRefPubMed
4.
Steckelbroeck S, Ballmer-Weber BK, Vieths S. Potential, pitfalls, and prospects of food allergy diagnostics with recombinant allergens or synthetic sequential epitopes. J Allergy Clin Immunol. 2008;121(6):1323–30.CrossRefPubMed
5.
Hoffmann-Sommergruber K, Mills EN, Vieths S. Coordinated and standardized production, purification and characterization of natural and recombinant food allergens to establish a food allergen library. Mol Nutr Food Res. 2008;52 Suppl 2:S159–65.CrossRefPubMed
6.
Sancho AI, Hoffmann-Sommergruber K, Alessandri S, Conti A, Giuffrida MG, Shewry P, et al. Authentication of food allergen quality by physicochemical and immunological methods. Clin Exp Allergy. 2010;40(7):973–86.CrossRefPubMed
7.
Hoffmann-Sommergruber K, Mills EN. Food allergen protein families and their structural characteristics and application in component-resolved diagnosis: new data from the EuroPrevall project. Anal Bioanal Chem. 2009;395(1):25–35.CrossRefPubMed
8.
Alessandri S, Sancho A, Vieths S, Mills CE, Wal JM, Shewry PR, et al. High-throughput NMR assessment of the tertiary structure of food allergens. PLoS One. 2012;7(7):e39785.PubMedCentralCrossRefPubMed
9.
10.
Radauer C, Nandy A, Ferreira F, Goodman RE, Larsen JN, Lidholm J, et al. Update of the WHO/IUIS allergen nomenclature database based on analysis of allergen sequences. Allergy. 2014;69(4):413–9.CrossRefPubMed
11.
Breiteneder H, Radauer C. A classification of plant food allergens. J Allergy Clin Immunol. 2004;113(5):821–30.CrossRefPubMed
12.
Radauer C, Breiteneder H. Evolutionary biology of plant food allergens. J Allergy Clin Immunol. 2007;120(3):518–25.CrossRefPubMed
13.
Jenkins JA, Breiteneder H, Mills EN. Evolutionary distance from human homologs reflects allergenicity of animal food proteins. J Allergy Clin Immunol. 2007;120(6):1399–405.CrossRefPubMed
14.
Larenas-Linnemann D, Cox LS. European allergen extract units and potency: review of available information. Ann Allergy Asthma Immunol. 2008;100(2):137–45.CrossRefPubMed
15.
Sander 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):1486–92.CrossRefPubMed
16.
Heinzerling L, Mari A, Bergmann KC, Bresciani M, Burbach G, Darsow U, et al. The skin prick test—European standards. Clin Transl Allergy. 2013;3(1):3.PubMedCentralCrossRefPubMed
17.
Bolhaar ST, van de Weg WE, van Ree R, Gonzalez-Mancebo E, Zuidmeer L, Bruijnzeel-Koomen CA, et al. In vivo assessment with prick-to-prick testing and double-blind, placebo-controlled food challenge of allergenicity of apple cultivars. J Allergy Clin Immunol. 2005;116(5):1080–6.CrossRefPubMed
18.
Ma Y, Zuidmeer L, Bohle B, Bolhaar ST, Gadermaier G, Gonzalez-Mancebo E, et al. Characterization of recombinant Mal d 4 and its application for component-resolved diagnosis of apple allergy. Clin Exp Allergy. 2006;36(8):1087–96.CrossRefPubMed
19.
Garcia BE, Gonzalez-Mancebo E, Barber D, Martin S, Tabar AI, de Durana AM D, et al. Sublingual immunotherapy in peach allergy: monitoring molecular sensitizations and reactivity to apple fruit and Platanus pollen. J Investig Allergol Clin Immunol. 2010;20(6):514–20.PubMed
20.•
Kollmann D, Geroldinger-Simic M, Kinaciyan T, Huber H, Ebner C, Lidholm J, et al. Recombinant Mal d 1 is a reliable diagnostic tool for birch pollen allergen-associated apple allergy. J Allergy Clin Immunol. 2013;132(4):1008–10. This is an interesting proof of concept study—using recombinant Mal d 1, obtained by GMP conditions successfully for SPT—showing the potential of recombinant allergen testing in vivo.CrossRefPubMed
21.
Asero R. Peach-induced contact urticaria is associated with lipid transfer protein sensitization. Int Arch Allergy Immunol. 2011;154(4):345–8.CrossRefPubMed
22.
Peeters KA, Koppelman SJ, Penninks AH, Lebens A, Bruijnzeel-Koomen CA, Hefle SL, et al. Clinical relevance of sensitization to lupine in peanut-sensitized adults. Allergy. 2009;64(4):549–55.CrossRefPubMed
23.
Flinterman AE, van Hoffen E, den Hartog Jager CF, Koppelman S, Pasmans SG, Hoekstra MO, et al. Children with peanut allergy recognize predominantly Ara h 2 and Ara h 6, which remains stable over time. Clin Exp Allergy. 2007;37(8):1221–8.CrossRefPubMed
24.
Chapman MD, Ferreira F, Villalba M, Cromwell O, Bryan D, Becker WM, et al. The European Union CREATE project: a model for international standardization of allergy diagnostics and vaccines. J Allergy Clin Immunol. 2008;122(5):882–9 e2.CrossRefPubMed
25.
Andersson K, Ballmer-Weber BK, Cistero-Bahima A, Ostling J, Lauer I, Vieths S, et al. Enhancement of hazelnut extract for IgE testing by recombinant allergen spiking. Allergy. 2007;62(8):897–904.CrossRefPubMed
26.
27.••
Eller E, Bindslev-Jensen C. Clinical value of component-resolved diagnostics in peanut-allergic patients. Allergy. 2013;68(2):190–4. This study compares the outcome of molecular diagnosis and DBPCFCs and highlights that application of molecular diagnosis can reduce the number of necessary DBPCFCs considerably. In this study, a cutoff for Ara h 2 >1.63 kU/L would have reduced the number of challenges performed from 205 to 92.CrossRefPubMed
28.••
Beyer K, Grabenhenrich L, Hartl M, Beder A, Kalb B, Ziegert M, et al. Predictive values of component-specific IgE for the outcome of peanut and hazelnut food challenges in children. Allergy. 2015;70(1):90–8. Prospective and multicenter German study, highlighting the predictive value of CRD in hazelnut and peanut allergy and reducing the number of necessary DBPCFCs accordingly.CrossRefPubMed
29.
Erdmann SM, Sachs B, Schmidt A, Merk HF, Scheiner O, Moll-Slodowy S, et al. In vitro analysis of birch-pollen-associated food allergy by use of recombinant allergens in the basophil activation test. Int Arch Allergy Immunol. 2005;136(3):230–8.CrossRefPubMed
30.
Sato S, Tachimoto H, Shukuya A, Ogata M, Komata T, Imai T, et al. Utility of the peripheral blood basophil histamine release test in the diagnosis of hen’s egg, cow’s milk, and wheat allergy in children. Int Arch Allergy Immunol. 2011;155 Suppl 1:96–103.CrossRefPubMed
31.•
Glaumann S, Nopp A, Johansson SG, Rudengren M, Borres MP, Nilsson C. Basophil allergen threshold sensitivity, CD-sens, IgE-sensitization and DBPCFC in peanut-sensitized children. Allergy. 2012;67(2):242–7. In a peanut allergic collective, results were obtained from basophil test, molecular diagnosis, and DBPCFCs. When comparing the results, negative BAT outcome and spIgE testing for peanut allergens were identified as safe, time-saving, and cost-effective complements to DBPCFCs.CrossRefPubMed
32.
Santos AF, Du Toit G, Douiri A, Radulovic S, Stephens A, Turcanu V, et al. Distinct parameters of the basophil activation test reflect the severity and threshold of allergic reactions to peanut. J Allergy Clin Immunol. 2015;135(1):179–86.PubMedCentralCrossRefPubMed
33.
Hochwallner H, Schulmeister U, Swoboda I, Spitzauer S, Valenta R. Cow’s milk allergy: from allergens to new forms of diagnosis, therapy and prevention. Methods. 2014;66(1):22–33.PubMedCentralCrossRefPubMed
34.
35.
Burney PG, Potts J, Kummeling I, Mills EN, Clausen M, Dubakiene R, et al. The prevalence and distribution of food sensitization in European adults. Allergy. 2014;69(3):365–71.CrossRefPubMed
36.
Fernandez-Rivas M, Bolhaar S, Gonzalez-Mancebo E, Asero R, van Leeuwen A, Bohle B, et al. Apple allergy across Europe: how allergen sensitization profiles determine the clinical expression of allergies to plant foods. J Allergy Clin Immunol. 2006;118(2):481–8.CrossRefPubMed
37.
Fernandez-Rivas M, Gonzalez-Mancebo E, Rodriguez-Perez R, Benito C, Sanchez-Monge R, Salcedo G, et al. Clinically relevant peach allergy is related to peach lipid transfer protein, Pru p 3, in the Spanish population. J Allergy Clin Immunol. 2003;112(4):789–95.CrossRefPubMed
38.••
Boyano-Martinez T, Pedrosa M, Belver T, Quirce S, Garcia-Ara C. Peach allergy in Spanish children: tolerance to the pulp and molecular sensitization profile. Pediatr Allergy Immunol. 2013;24(2):168–72. Oral food challenges were performed and results compared with CDR and SPTs using purified nPru p 3. Even with Pru p 3 sensitization, only a subset of patients reacted with peach during challenges. In addition, most of the patients tolerated peach pulp—showing that Pru p 3 is enriched in peach peel.CrossRefPubMed
39.
Pastorello EA, Farioli L, Stafylaraki C, Mascheri A, Scibilia J, Pravettoni V, et al. Anti-rPru p 3 IgE levels are inversely related to the age at onset of peach-induced severe symptoms reported by peach-allergic adults. Int Arch Allergy Immunol. 2013;162(1):45–9.CrossRefPubMed
40.
Bublin M, Dennstedt S, Buchegger M, Antonietta Ciardiello M, Bernardi ML, Tuppo L, et al. The performance of a component-based allergen microarray for the diagnosis of kiwifruit allergy. Clin Exp Allergy. 2011;41(1):129–36.CrossRefPubMed
41.
Bublin M, Pfister M, Radauer C, Oberhuber C, Bulley S, Dewitt AM, et al. Component-resolved diagnosis of kiwifruit allergy with purified natural and recombinant kiwifruit allergens. J Allergy Clin Immunol. 2010;125(3):687–94. 94 e1.CrossRefPubMed
42.••
Le TM, Bublin M, Breiteneder H, Fernandez-Rivas M, Asero R, Ballmer-Weber B, et al. Kiwifruit allergy across Europe: clinical manifestation and IgE recognition patterns to kiwifruit allergens. J Allergy Clin Immunol. 2013;131(1):164–71. This European study included 311 individuals from outpatient clinics. CRD highlighted different sensitization patterns in different geographic regions and correlated sensitization to Act d 1 with severe symptoms.CrossRefPubMed
43.
Bauermeister K, Ballmer-Weber BK, Bublin M, Fritsche P, Hanschmann KM, Hoffmann-Sommergruber K, et al. Assessment of component-resolved in vitro diagnosis of celeriac allergy. J Allergy Clin Immunol. 2009;124(6):1273–81. e2.CrossRefPubMed
44.
Gadermaier G, Egger M, Girbl T, Erler A, Harrer A, Vejvar E, et al. Molecular characterization of Api g 2, a novel allergenic member of the lipid-transfer protein 1 family from celery stalks. Mol Nutr Food Res. 2011;55(4):568–77.CrossRefPubMed
45.
Vejvar E, Himly M, Briza P, Eichhorn S, Ebner C, Hemmer W, et al. Allergenic relevance of nonspecific lipid transfer proteins 2: identification and characterization of Api g 6 from celery tuber as representative of a novel IgE-binding protein family. Mol Nutr Food Res. 2013;57(11):2061–70.CrossRefPubMed
46.••
Ballmer-Weber BK, Skamstrup Hansen K, Sastre J, Andersson K, Batscher I, Ostling J, et al. Component-resolved in vitro diagnosis of carrot allergy in three different regions of Europe. Allergy. 2012;67(6):758–66. Diagnosis of carrot allergy was assessed by DBPCFCs and CRD test sensitivity and specificity determined and compared to extract-based approach. This study highlighted different sensitization patterns in different geographic regions and between carrot-tolerant and carrot-allergic individuals.CrossRefPubMed
47.
Hansen KS, Ballmer-Weber BK, Sastre J, Lidholm J, Andersson K, Oberhofer H, et al. Component-resolved in vitro diagnosis of hazelnut allergy in Europe. J Allergy Clin Immunol. 2009;123(5):1134–41. 41 e1-3.CrossRefPubMed
48.••
Masthoff LJ, Mattsson L, Zuidmeer-Jongejan L, Lidholm J, Andersson K, Akkerdaas JH, et al. Sensitization to Cor a 9 and Cor a 14 is highly specific for a hazelnut allergy with objective symptoms in Dutch children and adults. J Allergy Clin Immunol. 2013;132(2):393–9. An important study showing the diagnostic value of spIgE against Cor a 9 and Cor a 14 for hazelnut allergic patients, both in adults and in children.
49.••
Datema MR, Zuidmeer-Jongejan L, Asero R, Barreales L, Belohlavkova S, de Blay F, et al. Hazelnut allergy across Europe dissected molecularly: a EuroPrevall outpatient clinic survey. J Allergy Clin Immunol. 2015. Prospective study recruiting participants form outpatient clinics. A subset of those underwent DBPCFCs. In parallel, sensitization pattern to 17 hazelnut allergens was assessed, and in addition, spIgE levels of Cor a 1, Cor a 2, Cor a 8, Cor a 9, Cor a 11, and Cor a 14 also Cor a 12 were assessed.
50.
Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol. 2007;120(3):638–46.CrossRefPubMed
51.••
Nicolaou N, Poorafshar M, Murray C, Simpson A, Winell H, Kerry G, et al. Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics. J Allergy Clin Immunol. 2010;125(1):191–7. e1-13. Birth cohort study, investigating peanut allergy versus peanut sensitization in 8-year-old children.CrossRefPubMed
52.
Hong X, Caruso D, Kumar R, Liu R, Liu X, Wang G, et al. IgE, but not IgG4, antibodies to Ara h 2 distinguish peanut allergy from asymptomatic peanut sensitization. Allergy. 2012;67(12):1538–46.PubMedCentralPubMed
53.•
Klemans RJ, Liu X, Knulst AC, Knol MJ, Gmelig-Meyling F, Borst E, et al. IgE binding to peanut components by four different techniques: Ara h 2 is the most relevant in peanut allergic children and adults. Clin Exp Allergy. 2013;43(8):967–74. This is the first part of two studies dealing with the diagnostic value of spIgE against Ara h 2 as a marker of peanut allergy.CrossRefPubMed
54.•
Klemans RJ, Knol EF, Bruijnzeel-Koomen CA, Knulst AC. The diagnostic accuracy of specific IgE to Ara h 6 in adults is as good as Ara h 2. Allergy. 2014;69(8):1112–4. This is the second part of a peanut study, identifying the role of Ara h 6, another 2S albumin from peanut, in in vitro diagnosis.CrossRefPubMed
55.
Ackerbauer D, Bublin M, Radauer C, Varga EM, Hafner C, Ebner C, et al. Component-resolved IgE profiles in Austrian patients with a convincing history of peanut allergy. Int Arch Allergy Immunol. 2015;166(1):13–24.CrossRefPubMed
56.
Ebisawa M, Moverare R, Sato S, Maruyama N, Borres MP, Komata T. Measurement of Ara h 1-, 2-, and 3-specific IgE antibodies is useful in diagnosis of peanut allergy in Japanese children. Pediatr Allergy Immunol. 2012;23(6):573–81.CrossRefPubMed
57.•
Ballmer-Weber BK, Lidholm J, Fernandez-Rivas M, Seneviratne S, Hanschmann KM, Vogel L, et al. IgE recognition patterns in peanut allergy are age dependent: perspectives of the EuroPrevall study. Allergy. 2015;70(4):391–407. European study on peanut allergy, including patients with positive DBPCFCs. Geographic and age-related differences were observed. Role of Ara h 2 as a marker allergen confirmed; sensitization to Ara h 1, 2, and 3 is acquired in childhood.CrossRefPubMed
58.
Muraro A, Hoffmann-Sommergruber K, Holzhauser T, Poulsen LK, Gowland MH, Akdis CA, et al. EAACI food allergy and anaphylaxis guidelines. Protecting consumers with food allergies: understanding food consumption, meeting regulations and identifying unmet needs. Allergy. 2014;69(11):1464–72.CrossRefPubMed
59.
Palacin A, Rodriguez J, Blanco C, Lopez-Torrejon G, Sanchez-Monge R, Varela J, et al. Immunoglobulin E recognition patterns to purified kiwifruit (Actinidinia deliciosa) allergens in patients sensitized to kiwi with different clinical symptoms. Clin Exp Allergy. 2008;38(7):1220–8.CrossRefPubMed
Metadata
Title
Applications of Molecular Diagnostic Testing in Food Allergy
Authors
Karin Hoffmann-Sommergruber
Sabine Pfeifer
Merima Bublin
Publication date
01-09-2015
Publisher
Springer US
Published in
Current Allergy and Asthma Reports / Issue 9/2015
Print ISSN: 1529-7322
Electronic ISSN: 1534-6315
DOI
https://doi.org/10.1007/s11882-015-0557-6

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