Component resolved diagnosis is a new concept in the investigation of pediatric allergic disease. The aim of the present paper is to review the available data on component resolved diagnosis with respect to implications for investigation of children with allergic disease. In most conditions head-to-head comparisons of component resolved diagnosis with traditional IgE testing have not been performed. Rather than alternatives the molecular methods should be seen as adjuncts to the cheaper traditional specific IgE tests. It may be appropriate to determine IgE antibodies to components as part of the diagnostic work-up in selected cases of peanut and birch pollen allergy and in hymenoptera allergy. However, cost benefit analyses of component resolved diagnosis compared with traditional work-up of allergy are needed. Prospectively planned protocols for assessment of the extent to which component resolved diagnosis may be able to improve the selection of children to immunotherapy and, thus, the efficacy of immunotherapy, are needed. Finally, studies of component resolved diagnosis with microarray technology in screening panels with hundreds of components should be undertaken before it can be determined to which extent such panel screening, if at all, may be helpful in children. 1. Introduction Traditionally, diagnosis of pediatric allergic disease is based on a careful and thorough history, skin prick testing, and assessment of specific IgE antibodies to allergens in the blood, and on provocation or elimination-provocation-elimination tests. By means of molecular methods over the last few years, it has become possible to measure IgE antibodies to specific components of allergens. The methods are designated as component-resolved diagnosis [1–4]. The molecular structures of many allergens have been characterized and are commercially available as recombinant products. This has focused attention on the need for assessment of the clinical application of the methods in pediatric populations; however, guidelines or consensus on their use have not been defined. The aims of this paper is to introduce the concept of component resolved diagnosis, to identify conditions in which the new diagnostic tool may be helpful in pediatric allergic disease, and to discuss conditions in which more evidence should be provided before large-scale use of the methods may be warranted. 2. Allergens and Components All protein component material possesses a potential for development of allergy. Proteins in allergen sources (e.g., peanuts, pollen, and hymenoptera) often contain several
References
[1]
J. Sastre, “Molecular diagnosis in allergy,” Clinical and Experimental Allergy, vol. 40, no. 10, pp. 1442–1460, 2010.
[2]
M. P. Borres, M. Ebisawa, and P. A. Eigenmann, “Use of allergen components begins a new era in pediatric allergology,” Pediatric Allergy and Immunology, vol. 22, no. 5, pp. 454–461, 2011.
[3]
M. Ferrer, M. L. Sanz, J. Sastre, et al., “Molecular diagnosis in allergologgy: application of the microarray technique,” Journal Allergology and Clinical Immunology, vol. 19, supplement 1, pp. 19–24, 2009.
[4]
J. Lidholm, B. K. Ballmer-Weber, A. Mari, and S. Vieths, “Component-resolved diagnostics in food allergy,” Current Opinion in Allergy and Clinical Immunology, vol. 6, no. 3, pp. 234–240, 2006.
[5]
A. E. Flinterman, E. van Hoffen, C. F. den Hartog Jager et al., “Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time,” Clinical and Experimental Allergy, vol. 37, no. 8, pp. 1221–1228, 2007.
[6]
R. A. McDermott, H. S. Porterfield, R. E. Mezayen et al., “Contribution of Ara h 2 to peanut-specific, immunoglobulin E-mediated, cell activation,” Clinical and Experimental Allergy, vol. 37, no. 5, pp. 752–763, 2007.
[7]
D. Mittag, J. Akkerdaas, B. K. Ballmer-Weber et al., “Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy,” Journal of Allergy and Clinical Immunology, vol. 114, no. 6, pp. 1410–1417, 2004.
[8]
N. Nicolaou, C. Murray, D. Belgrave, M. Poorafshar, A. Simpson, and A. Custovic, “Quantification of specific IgE to whole peanut extract and peanut components in prediction of peanut allergy,” Journal of Allergy and Clinical Immunology, vol. 127, no. 3, pp. 684–685, 2011.
[9]
A. Asarnoj, E. ？stblom, S. Ahlstedt et al., “Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen—results from the BAMSE birth cohort,” Allergy, vol. 65, no. 2, pp. 213–219, 2010.
[10]
E. A. Pastorello, S. Vieths, V. Pravettoni et al., “Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results,” Journal of Allergy and Clinical Immunology, vol. 109, no. 3, pp. 563–570, 2002.
[11]
K. S. Hansen, B. K. Ballmer-Weber, J. Sastre et al., “Component-resolved in vitro diagnosis of hazelnut allergy in Europe,” Journal of Allergy and Clinical Immunology, vol. 123, no. 5, pp. 1134–e3, 2009.
[12]
T. Komata, L. S？derstr？m, M. P. Borres, H. Tachimoto, and M. Ebisawa, “Usefulness of wheat and soybean specific IgE antibody titers for the diagnosis of food allergy,” Allergology International, vol. 58, no. 4, pp. 599–603, 2009.
[13]
K. Ito, M. Futamura, M. P. Borres et al., “IgE antibodies to ω-5 gliadin associate with immediate symptoms on oral wheat challenge in Japanese children,” Allergy, vol. 63, no. 11, pp. 1536–1542, 2008.
[14]
F. Battais, F. Pineau, Y. Popineau et al., “Food allergy to wheat: identification of immunogloglin E and immunoglobulin G-binding proteins with sequential extracts and purified proteins from wheat flour,” Clinical and Experimental Allergy, vol. 33, no. 7, pp. 962–970, 2003.
[15]
K. Ito, S. Sj？lander, S. Sato et al., “IgE to Gly m 5 and Gly m 6 is associated with severe allergic reactions to soybean in Japanese children,” Journal of Allergy and Clinical Immunology, vol. 128, no. 3, pp. 673–675, 2011.
[16]
T. Holzhauser, O. Wackermann, B. K. Ballmer-Weber et al., “Soybean (Glycine max) allergy in Europe: Gly？m 5 (β-conglycinin) and Gly？m 6 (glycinin) are potential diagnostic markers for severe allergic reactions to soy,” Journal of Allergy and Clinical Immunology, vol. 123, no. 2, pp. 452.e4–458.e4, 2009.
[17]
H. J. Park, J. H. Kim, J. E. Kim, et al., “Diagnostic value of the serum-specific IgE ratio of ?-5 gliadin to wheat in adult patients with wheat-induced anaphylaxis,” International Archives of Allergy and Immunology, vol. 157, no. 2, pp. 147–150, 2011.
[18]
P. Kosma, S. Sj？lander, E. Landgren, M. P. Borres, and G. Hedlin, “Severe reactions after the intake of soy drink in birch pollen-allergic children sensitized to Gly m 4,” Acta Paediatrica, vol. 100, no. 2, pp. 305–307, 2011.
[19]
A. H. Benhamou, J. C. Caubet, P. A. Eigenmann et al., “State of the art and new horizons in the diagnosis and management of egg allergy,” Allergy, vol. 65, no. 3, pp. 283–289, 2010.
[20]
H. Ando, R. Movérare, Y. Kondo et al., “Utility of ovomucoid-specific IgE concentrations in predicting symptomatic egg allergy,” Journal of Allergy and Clinical Immunology, vol. 122, no. 3, pp. 583–588, 2008.
[21]
H. Lemon-Mulé, H. A. Sampson, S. H. Sicherer, W. G. Shreffler, S. Noone, and A. Nowak-Wegrzyn, “Immunologic changes in children with egg allergy ingesting extensively heated egg,” Journal of Allergy and Clinical Immunology, vol. 122, no. 5, pp. 977.e1–983.e1, 2008.
[22]
T. Boyano-Martínez, C. García-Ara, M. Pedrosa, J. M. Díaz-Pena, and S. Quirce, “Accidental allergic reactions in children allergic to cow's milk proteins,” Journal of Allergy and Clinical Immunology, vol. 123, no. 4, pp. 883–888, 2009.
[23]
C. Constantin, S. Quirce, M. Poorafshar et al., “Micro-arrayed wheat seed and grass pollen allergens for component-resolved diagnosis,” Allergy, vol. 64, no. 7, pp. 1030–1037, 2009.
[24]
C. Hejl, P. A. Wurtzen, J. Kleine-Tebbe, N. Johansen, L. Broge, and H. Ipsen, “Phleum pratense alone is sufficient for allergen-specific immunotherapy against allergy to Pooideae grass pollens,” Clinical and Experimental Allergy, vol. 39, no. 5, pp. 752–759, 2009.
[25]
I. Swoboda, T. Twaroch, R. Valenta, and M. Grote, “Tree pollen allergens,” Clinical Allergy and Immunology, vol. 21, pp. 87–105, 2008.
[26]
G. Menz, C. Dolecek, U. Sch？nheit-Kenn et al., “Serological and skin-test diagnosis of birch pollen allergy with recombinant Bet v I, the major birch pollen allergen,” Clinical and Experimental Allergy, vol. 26, no. 1, pp. 50–60, 1996.
[27]
R. Movérare, K. Westritschnig, M. Svensson et al., “Different IgE reactivity profiles in birch pollen-sensitive patients from six European populations revealed by recombinant allergens: an imprint of local sensitization,” International Archives of Allergy and Immunology, vol. 128, no. 4, pp. 325–335, 2002.
[28]
N. Mothes and R. Valenta, “Biology of tree pollen allergens,” Current Allergy and Asthma Reports, vol. 4, no. 5, pp. 384–390, 2004.
[29]
A. Martínez, J. A. Asturias, J. Monteseirín et al., “The allergenic relevance of profilin (Ole e 2) from Olea europaea pollen,” Allergy, vol. 57, supplement 71, pp. 17–23, 2002.
[30]
R. Valenta, B. Hayek, S. Seiberler et al., “Calcium-binding allergens: from plants to man,” International Archives of Allergy and Immunology, vol. 117, no. 3, pp. 160–166, 1998.
[31]
G. Pittner, S. Vrtala, W. R. Thomas et al., “Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens,” Clinical and Experimental Allergy, vol. 34, no. 4, pp. 597–603, 2004.
[32]
J. Fernandes, A. Reshef, L. Patton, R. Ayuso, G. Reese, and S. B. Lehrer, “Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews,” Clinical and Experimental Allergy, vol. 33, no. 7, pp. 956–961, 2003.
[33]
H. Gr？nlund, T. Saarne, G. Gafvelin, and M. van Hage, “The major cat allergen, fel d 1, in diagnosis and therapy,” International Archives of Allergy and Immunology, vol. 151, no. 4, pp. 265–274, 2010.
[34]
C. Hilger, M. Kohnen, F. Grigioni, C. Lehners, and F. Hentges, “Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels,” Allergy, vol. 52, no. 2, pp. 179–187, 1997.
[35]
S. Saarelainen, A. Taivainen, M. Rytk？nen-Nissinen et al., “Assessment of recombinant dog allergens Can f 1 and Can f 2 for the diagnosis of dog allergy,” Clinical and Experimental Allergy, vol. 34, no. 10, pp. 1576–1582, 2004.
[36]
L. Mattsson, T. Lundgren, H. Everberg, H. Larsson, and J. Lidholm, “Prostatic kallikrein: a new major dog allergen,” Journal of Allergy and Clinical Immunology, vol. 123, no. 2, pp. 362.e3–368.e3, 2009.
[37]
R. Cabanas, M. C. Lopez-Serrano, J. Carreira, et al., “Importance of albumin in cross-reactivity among cat, dog and horse allergens,” Journal of Investigational Allergology and Clinical Immunology, vol. 10, pp. 71–77, 2000.
[38]
S. Saarelainen, M. Rytk？nen-Nissinen, J. Rouvinen et al., “Animal-derived lipocalin allergens exhibit immunoglobulin E cross-reactivity,” Clinical and Experimental Allergy, vol. 38, no. 2, pp. 374–381, 2008.
[39]
D. C. De Graaf, M. Aerts, E. Danneels, and B. Devreese, “Bee, wasp and ant venomics pave the way for a component-resolved diagnosis of sting allergy,” Journal of Proteomics, vol. 72, no. 2, pp. 145–154, 2009.
[40]
B. M. Biló, F. Rueff, H. Mosbech et al., “Diagnosis of Hymenoptera venom allergy,” Allergy, vol. 60, no. 11, pp. 1339–1349, 2005.
[41]
K. Skamstrup Hansen and L. K. Poulsen, “Component resolved testing for allergic sensitization,” Current Allergy and Asthma Reports, vol. 10, no. 5, pp. 340–348, 2010.
[42]
O. D. Wolthers and M. Staberg, “A comparison of the usefulness of the multiple allergen simultaneous test-chemiluminescent assay as compared to the phadia immunocap IgE test panel system in children and adolescents.,” Recent Patents on Inflammation & Allergy Drug Discovery. In press.
