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Proteomics for Allergy: from Proteins to the Patients

  • Allergens (RK Bush and JA Woodfolk, Section Editors)
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Abstract

Proteomics encompasses a variety of approaches unraveling both the structural features, post-translational modifications, and abundance of proteins. As of today, proteomic studies have shed light on the primary structure of about 850 allergens, enabling the design of microarrays for improved molecular diagnosis. Proteomic methods including mass spectrometry allow as well to investigate protein-protein interactions, thus yielding precise information on critical epitopes on the surface of allergens. Mass spectrometry is now being applied to the unambiguous identification, characterization, and comprehensive quantification of allergens in a variety of matrices, as diverse as food samples and allergen immunotherapy drug products. As such, it represents a method of choice for quality testing of allergen immunotherapy products.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Kenyon GL, DeMarini DM, Fuchs E, Galas DJ, Kirsch JF, Leyh TS, et al. Defining the mandate of proteomics in the post-genomics era: workshop report. Mol Cellular Proteomics. 2002;1(10):763–80.

    CAS  Google Scholar 

  2. The UniProt Consortium. UniProt: a hub for protein information. Nucleic Acids Res 2015;43:D204-212.

  3. Szefler SJ, Wenzel S, Brown R, Erzurum SC, Fahy JV, Hamilton RG, et al. Asthma outcomes: biomarkers. J Allergy Clin Immunol. 2012;129(3 Suppl):S9–23.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Paczesny S. Discovery and validation of graft-versus-host disease biomarkers. Blood. 2013;121(4):585–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yeat NC, Lin C, Sager M, Lin J. Cancer proteomics: developments in technology, clinical use and commercialization. Expert Rev Proteomics. 2015;12(4):391–405.

    Article  CAS  PubMed  Google Scholar 

  6. Mohan C, Assassi S. Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity? BMJ. 2015;351:5079.

    Article  Google Scholar 

  7. Lindsey ML, Mayr M, Gomes AV, Delles C, Arrell DK, Murphy AM, et al. Transformative impact of proteomics on cardiovascular health and disease: a scientific statement from the American heart association. Circulation. 2015;132(9):852–72.

    Article  CAS  PubMed  Google Scholar 

  8. Bousquet J, Anto JM, Akdis M, Auffray C, Keil T, Momas I, et al. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story. Allergy 2016. doi:10.1111/all.12880. Combination of epigenetics, proteomics, transcriptomics and IgE micro-array to better manage allergic diseases.

  9. Nathan RA, Meltzer EO, Derebery J, Campbell UB, Stang PE, Corrao MA, et al. The prevalence of nasal symptoms attributed to allergies in the United States: findings from the burden of rhinitis in an America survey. Allergy Asthma Proc. 2008;29(6):600–8.

    Article  PubMed  Google Scholar 

  10. Ait-Khaled N, Pearce N, Anderson HR, Ellwood P, Montefort S, Shah J. Global map of the prevalence of symptoms of rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC) phase three. Allergy. 2009;64(1):123–48.

    Article  CAS  PubMed  Google Scholar 

  11. Gupta RS, Springston EE, Warrier MR, Smith B, Kumar R, Pongracic J, et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011;128(1):9–17.

    Article  Google Scholar 

  12. Calderon MA, Demoly P, Gerth van Wijk R, Bousquet J, Sheikh A, Frew A, et al. EAACI: a European declaration on immunotherapy. Designing the future of allergen specific immunotherapy. Clin Transl Allergy. 2012;2(1):20.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133(2):291–307. Review on the epidemiology, pathogenesis, diagnosis, and treatment of food allergy.

    Article  CAS  PubMed  Google Scholar 

  14. 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. Public database with official systematic nomenclature of allergenic proteins and links to proteomics resources.

    Article  CAS  PubMed  Google Scholar 

  15. Lowenstein H. Quantitative immunoelectrophoretic methods as a tool for the analysis and isolation of allergens. Prog Allergy. 1978;25:1–62.

    CAS  PubMed  Google Scholar 

  16. Niall HD. Automated Edman degradation: the protein sequenator. Methods Enzymol. 1973;27:942–1010.

    Article  CAS  PubMed  Google Scholar 

  17. Simpson RJ, Nice EC, Moritz RL, Stewart GA. Structural studies on the allergen Der p 1 from the house dust mite Dermatophagoides pteronyssinus: similarity with cysteine proteinases. Protein Seq Data Anal. 1989;2(1):17–21.

    CAS  PubMed  Google Scholar 

  18. Villalba M, Batanero E, Lopez-Otin C, Sanchez LM, Monsalve RI, de la Pena MA G, et al. The amino acid sequence of Ole e I, the major allergen from olive tree (Olea europaea) pollen. Eur J Biochem. 1993;216(3):863–9.

    Article  CAS  PubMed  Google Scholar 

  19. Kettner A, Hughes GJ, Frutiger S, Astori M, Roggero M, Spertini F, et al. Api m 6: a new bee venom allergen. J Allergy Clin Immunol. 2001;107(5):914–20.

    Article  CAS  PubMed  Google Scholar 

  20. Swoboda I, Jilek A, Ferreira F, Engel E, Hoffmann-Sommergruber K, Scheiner O, et al. Isoforms of Bet v 1, the major birch pollen allergen, analyzed by liquid chromatography, mass spectrometry, and cDNA cloning. J Biol Chem. 1995;270(6):2607–13.

    Article  CAS  PubMed  Google Scholar 

  21. Kristensen AK, Schou C, Roepstorff P. Determination of isoforms, N-linked glycan structure and disulfide bond linkages of the major cat allergen Fel d1 by a mass spectrometric approach. Biol Chem. 1997;378(8):899–908.

    CAS  PubMed  Google Scholar 

  22. Helsper JP, Gilissen LJ, van Ree R, America AH, Cordewener JH, Bosch D. Quadrupole time-of-flight mass spectrometry: a method to study the actual expression of allergen isoforms identified by PCR cloning. J Allergy Clin Immunol. 2002;110(1):131–8.

    Article  CAS  PubMed  Google Scholar 

  23. Shefcheck KJ, Musser SM. Confirmation of the allergenic peanut protein, Ara h 1, in a model food matrix using liquid chromatography/tandem mass spectrometry (LC/MS/MS). Journal of Agric Food Chem. 2004;52(10):2785–90.

    Article  CAS  Google Scholar 

  24. Natale M, Bisson C, Monti G, Peltran A, Garoffo LP, Valentini S, et al. Cow’s milk allergens identification by two-dimensional immunoblotting and mass spectrometry. Mol Nutr Food Res. 2004;48(5):363–9.

    Article  CAS  PubMed  Google Scholar 

  25. Abdel Rahman AM, Kamath SD, Lopata AL, Robinson JJ, Helleur RJ. Biomolecular characterization of allergenic proteins in snow crab (Chionoecetes opilio) and de novo sequencing of the second allergen arginine kinase using tandem mass spectrometry. J Proteomics. 2011;74(2):231–41.

    Article  CAS  PubMed  Google Scholar 

  26. Downs ML, Baumert JL, Taylor SL, Mills EN. Mass spectrometric analysis of allergens in roasted walnuts. J Proteomics. 2016;142:62–9.

    Article  CAS  PubMed  Google Scholar 

  27. Batanero E, Villalba M, Monsalve RI, Rodriguez R. Cross-reactivity between the major allergen from olive pollen and unrelated glycoproteins: evidence of an epitope in the glycan moiety of the allergen. J Allergy Clin Immunol. 1996;97(6):1264–71.

    Article  CAS  PubMed  Google Scholar 

  28. Aalberse RC. Clinical relevance of carbohydrate allergen epitopes. Allergy. 1998;53(45 Suppl):54–7.

    Article  CAS  PubMed  Google Scholar 

  29. Kolarich D, Altmann F. N-Glycan analysis by matrix-assisted laser desorption/ionization mass spectrometry of electrophoretically separated nonmammalian proteins: application to peanut allergen Ara h 1 and olive pollen allergen Ole e 1. Anal Biochem. 2000;285(1):64–75.

    Article  CAS  PubMed  Google Scholar 

  30. Dumez ME, Teller N, Mercier F, Tanaka T, Vandenberghe I, Vandenbranden M, et al. Activation mechanism of recombinant Der p 3 allergen zymogen: contribution of cysteine protease Der p 1 and effect of propeptide glycosylation. J Biol Chem. 2008;283(45):30606–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fenaille F, Nony E, Chabre H, Lautrette A, Couret MN, Batard T, et al. Mass spectrometric investigation of molecular variability of grass pollen group 1 allergens. J Proteome Res. 2009;8(8):4014–27.

    Article  CAS  PubMed  Google Scholar 

  32. Almond RJ, Flanagan BF, Antonopoulos A, Haslam SM, Dell A, Kimber I, et al. Differential immunogenicity and allergenicity of native and recombinant human lactoferrins: role of glycosylation. Eur J Immunol. 2013;43(1):170–81.

    Article  CAS  PubMed  Google Scholar 

  33. Berg EA, Platts-Mills TA, Commins SP. Drug allergens and food—the cetuximab and galactose-alpha-1,3-galactose story. Ann Allergy Asthma Immunol. 2014;112(2):97–101.

    Article  CAS  PubMed  Google Scholar 

  34. Soh WT, Le Mignon M, Suratannon N, Satitsuksanoa P, Chatchatee P, Wongpiyaboron J, et al. The house dust mite major allergen Der p 23 displays O-glycan-independent IgE reactivities but no chitin-binding activity. Int Arch Allergy Immunol. 2015;168(3):150–60.

    Article  CAS  PubMed  Google Scholar 

  35. Chen JQ, Heldman MR, Herrmann MA, Kedei N, Woo W, Blumberg PM, et al. Absolute quantitation of endogenous proteins with precision and accuracy using a capillary Western system. Anal Biochem. 2013;442(1):97–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hamm M, Ha S, Rustandi RR. Automated capillary Western dot blot method for the identity of a 15-valent pneumococcal conjugate vaccine. Anal Biochem. 2015;478:33–9.

    Article  CAS  PubMed  Google Scholar 

  37. Hoofnagle AN, Wener MH. The fundamental flaws of immunoassays and potential solutions using tandem mass spectrometry. J Immunol Methods. 2009;347(1-2):3–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Svobodova M, Mairal T, Nadal P, Bermudo MC, O’Sullivan CK. Ultrasensitive aptamer based detection of beta-conglutin food allergen. Food Chem. 2014;165:419–23.

    Article  CAS  PubMed  Google Scholar 

  39. Monaci L, Losito I, Palmisano F, Visconti A. Identification of allergenic milk proteins markers in fined white wines by capillary liquid chromatography-electrospray ionization-tandem mass spectrometry. J Chromatogr A. 2010;1217(26):4300–5.

    Article  CAS  PubMed  Google Scholar 

  40. Faeste CK, Ronning HT, Christians U, Granum PE. Liquid chromatography and mass spectrometry in food allergen detection. J Food Prot. 2011;74(2):316–45.

    Article  CAS  PubMed  Google Scholar 

  41. Monaci L, Pilolli R, De Angelis E, Godula M, Visconti A. Multi-allergen detection in food by micro high-performance liquid chromatography coupled to a dual cell linear ion trap mass spectrometry. J Chromatogr A. 2014;1358:136–44.

    Article  CAS  PubMed  Google Scholar 

  42. Gomaa A, Boye J. Simultaneous detection of multi-allergens in an incurred food matrix using ELISA, multiplex flow cytometry and liquid chromatography mass spectrometry (LC-MS). Food Chem. 2015;175:585–92. Comparability of ELISA, LC-MS and multiplex flow cytometry methods for the detection of multiple allergens.

    Article  CAS  PubMed  Google Scholar 

  43. Petersen A, Suck R, Lindner B, Georgieva D, Ernst M, Notbohm H, et al. Phl p 3: structural and immunological characterization of a major allergen of timothy grass pollen. Clin Exp Allergy. 2006;36(6):840–9.

    Article  CAS  PubMed  Google Scholar 

  44. Schmidt H, Krause S, Gelhaus C, Petersen A, Janssen O, Becker WM. Detection and structural characterization of natural Ara h 7, the third peanut allergen of the 2S albumin family. J Proteome Res. 2010;9(7):3701–9.

    Article  CAS  PubMed  Google Scholar 

  45. Bouley J, Groeme R, Le Mignon M, Jain K, Chabre H, Bordas-Le Floch V, et al. Identification of the cysteine protease Amb a 11 as a novel major allergen from short ragweed. J Allergy Clin Immunol. 2015;136(4):1055–64.

    Article  CAS  PubMed  Google Scholar 

  46. Schulten V, Greenbaum JA, Hauser M, McKinney DM, Sidney J, Kolla R, et al. Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals. Proc Natl Acad Sci U S A. 2013;110(9):3459–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Bordas-Le Floch V, Le Mignon M, Bouley J, Groeme R, Jain K, Baron-Bodo V, et al. Identification of novel short ragweed pollen allergens using combined transcriptomic and immunoproteomic approaches. PLoS One. 2015;10(8), e0136258.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Batard T, Baron-Bodo V, Martelet A, Le Mignon M, Lemoine P, Jain K, et al. Patterns of IgE sensitization in house dust mite-allergic patients: implications for allergen immunotherapy. Allergy. 2016;71(2):220–9.

    Article  CAS  PubMed  Google Scholar 

  49. Meno KH. Allergen structures and epitopes. Allergy. 2011;66 Suppl 95:19–21.

    Article  PubMed  Google Scholar 

  50. Westernberg L, Schulten V, Greenbaum JA, Natali S, Tripple V, McKinney DM, et al. T-cell epitope conservation across allergen species is a major determinant of immunogenicity. J Allergy Clin Immunol 2016;138(2):571–578.e7.

  51. Klimek L, Pfaar O, Worm M. New opportunities for allergen immunotherapy using synthetic peptide immuno-regulatory epitopes (SPIREs). Expert Rev Clin Immunol. 2016.

  52. Spangfort MD, Mirza O, Ipsen H, Van Neerven RJ, Gajhede M, Larsen JN. Dominating IgE-binding epitope of Bet v 1, the major allergen of birch pollen, characterized by X-ray crystallography and site-directed mutagenesis. J Immunol. 2003;171(6):3084–90.

    Article  CAS  PubMed  Google Scholar 

  53. Ichikawa S, Takai T, Inoue T, Yuuki T, Okumura Y, Ogura K, et al. NMR study on the major mite allergen Der f 2: its refined tertiary structure, epitopes for monoclonal antibodies and characteristics shared by ML protein group members. J Biochem. 2005;137(3):255–63.

    Article  CAS  PubMed  Google Scholar 

  54. Padavattan S, Flicker S, Schirmer T, Madritsch C, Randow S, Reese G, et al. High-affinity IgE recognition of a conformational epitope of the major respiratory allergen Phl p 2 as revealed by X-ray crystallography. J Immunol. 2009;182(4):2141–51.

    Article  CAS  PubMed  Google Scholar 

  55. Tan KW, Ong TC, Gao YF, Tiong YS, Wong KN, Chew FT, et al. NMR structure and IgE epitopes of Blo t 21, a major dust mite allergen from Blomia tropicalis. J Biol Chem. 2012;287(41):34776–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gieras A, Cejka P, Blatt K, Focke-Tejkl M, Linhart B, Flicker S, et al. Mapping of conformational IgE epitopes with peptide-specific monoclonal antibodies reveals simultaneous binding of different IgE antibodies to a surface patch on the major birch pollen allergen, Bet v 1. J Immunol. 2011;186(9):5333–44.

    Article  CAS  PubMed  Google Scholar 

  57. Ebner C, Szepfalusi Z, Ferreira F, Jilek A, Valenta R, Parronchi P, et al. Identification of multiple T cell epitopes on Bet v I, the major birch pollen allergen, using specific T cell clones and overlapping peptides. J Immuno. 1993;150(3):1047–54.

    CAS  Google Scholar 

  58. van Milligen FJ, van ’t Hof W, van den Berg M, Aalberse RC. IgE epitopes on the cat (Felis domesticus) major allergen Fel d I: a study with overlapping synthetic peptides. J Allergy Clin Immunol. 1994;93(1):34–43.

    Article  PubMed  Google Scholar 

  59. Miyaji K, Yurimoto T, Saito A, Yasueda H, Takase Y, Shimakura H, et al. Analysis of conformational and sequential IgE epitopes on the major allergen Cry j 2 of Japanese cedar (Cryptomeria japonica) pollen in humans by using monoclonal antibodies for Cry j 2. J Clin Immunol. 2013;33(5):977–83.

    Article  CAS  PubMed  Google Scholar 

  60. Arnon R, Van Regenmortel MH. Structural basis of antigenic specificity and design of new vaccines. Faseb J. 1992;6(14):3265–74.

    CAS  PubMed  Google Scholar 

  61. Coales SJ, Tuske SJ, Tomasso JC, Hamuro Y. Epitope mapping by amide hydrogen/deuterium exchange coupled with immobilization of antibody, on-line proteolysis, liquid chromatography and mass spectrometry. Rapid Commun Mass Spectrom. 2009;23(5):639–47.

    Article  CAS  PubMed  Google Scholar 

  62. Zhang Q, Willison LN, Tripathi P, Sathe SK, Roux KH, Emmett MR, et al. Epitope mapping of a 95 kDa antigen in complex with antibody by solution-phase amide backbone hydrogen/deuterium exchange monitored by Fourier transform ion cyclotron resonance mass spectrometry. Anal Chem. 2011;83(18):7129–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Malito E, Faleri A, Lo Surdo P, Veggi D, Maruggi G, Grassi E, et al. Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen. Proc Natl Acad Sci U S A. 2013;110(9):3304–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Houde D, Engen JR. Conformational analysis of recombinant monoclonal antibodies with hydrogen/deuterium exchange mass spectrometry. Methods Mol Biol. 2013;988:269–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Chapman MD, Heymann PW, Platts-Mills TA. Epitope mapping of two major inhalant allergens, Der p I and Der f I, from mites of the genus Dermatophagoides. J Immunol. 1987;139(5):1479–84.

    CAS  PubMed  Google Scholar 

  66. Chruszcz M, Chapman MD, Vailes LD, Stura EA, Saint-Remy JM, Minor W, et al. Crystal structures of mite allergens Der f 1 and Der p 1 reveal differences in surface-exposed residues that may influence antibody binding. J Mol Biol. 2009;386(2):520–30.

    Article  CAS  PubMed  Google Scholar 

  67. Chruszcz M, Pomes A, Glesner J, Vailes LD, Osinski T, Porebski PJ, et al. Molecular determinants for antibody binding on group 1 house dust mite allergens. J Biol Chem. 2012;287(10):7388–98.

    Article  CAS  PubMed  Google Scholar 

  68. Peters RL, Allen KJ, Dharmage SC, Tang ML, Koplin JJ, Ponsonby AL, et al. Skin prick test responses and allergen-specific IgE levels as predictors of peanut, egg, and sesame allergy in infants. J Allergy Clin Immunol. 2013;132(4):874–80.

    Article  CAS  PubMed  Google Scholar 

  69. Tversky JR, Chelladurai Y, McGready J, Hamilton RG. Performance and pain tolerability of current diagnostic allergy skin prick test devices. J Allergy Clin Immunol Pract. 2015;3(6):888–93.

    Article  PubMed  Google Scholar 

  70. Tanno LK, Calderon MA, Papadopoulos NG, Sanchez-Borges M, Moon HB, Sisul JC, et al. Surveying the new allergic and hypersensitivity conditions chapter of the international classification of diseases (ICD)-11. Allergy. 2016.

  71. Ewan PW, Coote D. Evaluation of a capsulated hydrophilic carrier polymer (the ImmunoCAP) for measurement of specific IgE antibodies. Allergy. 1990;45(1):22–9.

    Article  CAS  PubMed  Google Scholar 

  72. Canonica GW, Ansotegui IJ, Pawankar R, Schmid-Grendelmeier P, van Hage M, Baena-Cagnani CE, et al. A WAO—ARIA—GA(2)LEN consensus document on molecular-based allergy diagnostics. World Allergy Organ J. 2013;6(1):17. A guide for the indications, determination, and interpretation of molecular-based allergy diagnostics for clinicians.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Lupinek C, Wollmann E, Baar A, Banerjee S, Breiteneder H, Broecker BM, et al. Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip. Methods. 2014;66(1):106–19.

    Article  CAS  PubMed  Google Scholar 

  74. Stringari G, Tripodi S, Caffarelli C, Dondi A, Asero R, Di Rienzo Businco A, et al. The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever. J Allergy Clin Immunol. 2014;134(1):75–81. The impact of component-resolved diagnosis on AIT prescription.

    Article  PubMed  Google Scholar 

  75. Khinchi MS, Poulsen LK, Carat F, Andre C, Hansen AB, Malling HJ. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study. Allergy. 2004;59(1):45–53.

    Article  CAS  PubMed  Google Scholar 

  76. Dahl R, Kapp A, Colombo G, de Monchy JG, Rak S, Emminger W, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006;118(2):434–40.

    Article  CAS  PubMed  Google Scholar 

  77. Frew AJ, Powell RJ, Corrigan CJ, Durham SR. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol. 2006;117(2):319–25.

    Article  CAS  PubMed  Google Scholar 

  78. Didier A, Malling HJ, Worm M, Horak F, Jager S, Montagut A, et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol. 2007;120(6):1338–45.

    Article  CAS  PubMed  Google Scholar 

  79. Powell RJ, Frew AJ, Corrigan CJ, Durham SR. Effect of grass pollen immunotherapy with Alutard SQ on quality of life in seasonal allergic rhinoconjunctivitis. Allergy. 2007;62(11):1335–8.

    Article  CAS  PubMed  Google Scholar 

  80. Dahl R, Kapp A, Colombo G, de Monchy JG, Rak S, Emminger W, et al. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J Allergy Clin Immunol. 2008;121(2):512–8.

    Article  CAS  PubMed  Google Scholar 

  81. Cox LS, Casale TB, Nayak AS, Bernstein DI, Creticos PS, Ambroisine L, et al. Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the importance of allergen-specific serum IgE. J Allergy Clin Immunol. 2012;130(6):1327–34.

    Article  CAS  PubMed  Google Scholar 

  82. Worm M, Rak S, de Blay F, Malling HJ, Melac M, Cadic V, et al. Sustained efficacy and safety of a 300IR daily dose of a sublingual solution of birch pollen allergen extract in adults with allergic rhinoconjunctivitis: results of a double-blind, placebo-controlled study. Clin Transl Allergy. 2014;4(1):7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1–55.

    Article  PubMed  Google Scholar 

  84. Esch RE, Plunkett GA. Immunotherapy preparation guidelines, rules, and regulation. Allergy Asthma Rep. 2013;13(4):406–13.

    Article  CAS  Google Scholar 

  85. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/ WC500003333.pdf.

  86. Krause B, Seifert S, Panne U, Kneipp J, Weidner SM. Matrix-assisted laser desorption/ionization mass spectrometric investigation of pollen and their classification by multivariate statistics. Rapid Commun Mass Spectrom. 2012;26(9):1032–8.

    Article  CAS  PubMed  Google Scholar 

  87. Lay Jr JO, Holland RD. Rapid identification of bacteria based on spectral patterns using MALDI-TOFMS. Methods Mol Biol. 2000;146:461–87.

    CAS  PubMed  Google Scholar 

  88. Machen A, Drake T, Wang YF. Same day identification and full panel antimicrobial susceptibility testing of bacteria from positive blood culture bottles made possible by a combined lysis-filtration method with MALDI-TOF VITEK mass spectrometry and the VITEK2 system. PLoS One. 2014;9(2):87870.

    Article  CAS  Google Scholar 

  89. Altun O, Botero-Kleiven S, Carlsson S, Ullberg M, Ozenci V. Rapid identification of bacteria from positive blood culture bottles by MALDI-TOF MS following short-term incubation on solid media. J Med Microbiol. 2015;64(11):1346–52.

    Article  PubMed  Google Scholar 

  90. van Ree R. The CREATE project: EU support for the improvement of allergen standardization in Europe. Allergy. 2004;59(6):571–4.

    Article  PubMed  Google Scholar 

  91. Himly M, Nony E, Chabre H, Van Overtvelt L, Neubauer A, van Ree R, et al. Standardization of allergen products: 1. Detailed characterization of GMP-produced recombinant Bet v 1.0101 as biological reference preparation. Allergy. 2009;64(7):1038–45.

    Article  CAS  PubMed  Google Scholar 

  92. Lowenstein H. Characterization and standardization of allergen extracts. Chem Immunol Allergy. 2014;100:323–32.

    Article  PubMed  Google Scholar 

  93. Himly M, Nandy A, Kahlert H, Thilker M, Steiner M, Briza P, et al. Standardization of allergen products: 2. Detailed characterization of GMP-produced recombinant Phl p 5.0109 as European pharmacopoeia reference standard. Allergy. 2016;71(4):495–504. The importance of proteomics methods for the establishment of well-characterized allergen reference standards.

    Article  CAS  PubMed  Google Scholar 

  94. Kaul S, Zimmer J, Dehus O, Costanzo A, Daas A, Buchheit KH, et al. Standardization of allergen products: 3. validation of candidate european pharmacopoeia standard methods for quantification of major birch allergen bet v 1. Allergy 2016

  95. Nony E, Bouley J, Le Mignon M, Lemoine P, Jain K, Horiot S, et al. Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen-allergic patients. Allergy. 2015;70(7):795–804.

    Article  CAS  PubMed  Google Scholar 

  96. Careri M, Costa A, Elviri L, Lagos JB, Mangia A, Terenghi M, et al. Use of specific peptide biomarkers for quantitative confirmation of hidden allergenic peanut proteins Ara h 2 and Ara h 3/4 for food control by liquid chromatography-tandem mass spectrometry. Anal Bioanal Chem. 2007;389(6):1901–7.

    Article  CAS  PubMed  Google Scholar 

  97. Seppala U, Dauly C, Robinson S, Hornshaw M, Larsen JN, Ipsen H. Absolute quantification of allergens from complex mixtures: a new sensitive tool for standardization of allergen extracts for specific immunotherapy. J Proteome Res. 2011;10(4):2113–22.

    Article  CAS  PubMed  Google Scholar 

  98. Houston NL, Lee DG, Stevenson SE, Ladics GS, Bannon GA, McClain S, et al. Quantitation of soybean allergens using tandem mass spectrometry. J Proteome Res. 2011;10(2):763–73.

    Article  CAS  PubMed  Google Scholar 

  99. Kuppannan K, Albers DR, Schafer BW, Dielman D, Young SA. Quantification and characterization of maize lipid transfer protein, a food allergen, by liquid chromatography with ultraviolet and mass spectrometric detection. Anal Chem. 2011;83(2):516–24.

    Article  CAS  PubMed  Google Scholar 

  100. Koeberl M, Clarke D, Lopata AL. Next generation of food allergen quantification using mass spectrometric systems. J Proteome Res. 2014;13(8):3499–509. A review of state-of-the-art approaches to quantify food allergens.

    Article  CAS  PubMed  Google Scholar 

  101. Briza P. The potential of mass spectrometry as a novel tool in standardization of natural allergen extracts. Arbeiten Paul-Ehrlich-Institut. 2013;97:57–62.

    CAS  Google Scholar 

  102. Barr JR, Maggio VL, Patterson Jr DG, Cooper GR, Henderson LO, Turner WE, et al. Isotope dilution—mass spectrometric quantification of specific proteins: model application with apolipoprotein A-I. Clin Chem. 1996;42(10):1676–82.

    CAS  PubMed  Google Scholar 

  103. Batard T, Nony E, Chabre H, Hrabina M, Bouley J, Lemignon M, et al. Molecular and functional characterization of natural allergen extracts. Arbeiten Paul-Ehrlich-Institut. 2013;97:54–6.

    Google Scholar 

  104. Trusheim MR, Berndt ER, Douglas FL. Stratified medicine: strategic and economic implications of combining drugs and clinical biomarkers. Nat Rev Drug Discov. 2007;6(4):287–93.

    Article  CAS  PubMed  Google Scholar 

  105. Senna G, Calderon M, Makatsori M, Ridolo E, Passalacqua G. An evidence-based appraisal of the surrogate markers of efficacy of allergen immunotherapy. Curr Opin Allergy Clin Immunol. 2011;11(4):375–80.

    Article  CAS  PubMed  Google Scholar 

  106. Moingeon P. Update on immune mechanisms associated with sublingual immunotherapy: practical implications for the clinician. J Allergy Clin Immunol Pract. 2013;1(3):228–41.

    Article  PubMed  Google Scholar 

  107. Shamji MH, Ljorring C, Wurtzen PA. Predictive biomarkers of clinical efficacy of allergen-specific immunotherapy: how to proceed. Immunotherapy. 2013;5(3):203–6.

    Article  CAS  PubMed  Google Scholar 

  108. Willis JC, Lord GM. Immune biomarkers: the promises and pitfalls of personalized medicine. Nature reviews. Immunology. 2015;15(5):323–9.

    CAS  PubMed  Google Scholar 

  109. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69(3):89-95. doi:10.1067/mcp.2001.113989.

  110. Shamji MH, Ljorring C, Francis JN, Calderon MA, Larche M, Kimber I, et al. Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy. Allergy. 2012;67(2):217–26.

    Article  CAS  PubMed  Google Scholar 

  111. Moingeon P. Biomarkers for allergen immunotherapy: a “Panoromic” view. Immunol Allergy Clin North Am. 2016;36(1):161–79. Up-to-date review on the combination of omics methods to identify novel putative BMKs of AIT.

    Article  PubMed  Google Scholar 

  112. Zimmer A, Bouley J, Le Mignon M, Pliquet E, Horiot S, Turfkruyer M, et al. A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy. J Allergy Clin Immunol. 2012;129(4):1020–30.

    Article  CAS  PubMed  Google Scholar 

  113. Gueguen C, Bouley J, Moussu H, Luce S, Duchateau M, Chamot-Rooke J, et al. Changes in markers associated with dendritic cells driving the differentiation of either TH2 cells or regulatory T cells correlate with clinical benefit during allergen immunotherapy. J Allergy Clin Immunol. 2016;137(2):545–58.

    Article  CAS  PubMed  Google Scholar 

  114. Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Devillier P, Montagut A, et al. Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. J Allergy Clin Immunol. 2009;124(3):471–7. 477 e471.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Stallergenes Greer, Research Department, 6 rue Alexis de Tocqueville, 92183, Antony cedex, France

    Emmanuel Nony, Maxime Le Mignon, Sébastien Brier, Armelle Martelet & Philippe Moingeon

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  1. Emmanuel Nony
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  2. Maxime Le Mignon
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  3. Sébastien Brier
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  4. Armelle Martelet
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  5. Philippe Moingeon
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Correspondence to Emmanuel Nony.

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Conflict of Interest

Dr. Moingeon reports funding from Stallergenes Greer and has a patent identity test by MS pending. Dr. Le Mignon reports personal fees from Stallergenes SAS. Dr. Nony has a patent method for Grass Species Identification issued to Stallergenes SAS, a patent sialylated fetuin A as a marker of immunotherapy efficacy pending to Stallergenes SAS, and a patent biomarker of immunotherapy efficacy pending to Stallergenes SAS. Dr. Martelet reports personal fees from Stallergenes SAS.

Human and Animal Rights and Informed Consent

This article does not contain any studies with animal subjects performed by the authors. With regard to the authors’ research cited in this paper, all procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000 and 2008.

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This article is part of the Topical Collection on Allergens

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Nony, E., Le Mignon, M., Brier, S. et al. Proteomics for Allergy: from Proteins to the Patients. Curr Allergy Asthma Rep 16, 64 (2016). https://doi.org/10.1007/s11882-016-0642-5

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  • DOI: https://doi.org/10.1007/s11882-016-0642-5

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