Proteomics for Allergy: from Proteins to the Patients

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.

[1]  J. Bousquet,et al.  A WAO - ARIA - GA²LEN consensus document on molecular-based allergy diagnostics , 2013, The World Allergy Organization journal.

[2]  S. Musser,et al.  Confirmation of the allergenic peanut protein, Ara h 1, in a model food matrix using liquid chromatography/tandem mass spectrometry (LC/MS/MS). , 2004, Journal of agricultural and food chemistry.

[3]  L L Needham,et al.  Isotope dilution--mass spectrometric quantification of specific proteins: model application with apolipoprotein A-I. , 1996, Clinical chemistry.

[4]  Rosa Pilolli,et al.  Multi-allergen detection in food by micro high-performance liquid chromatography coupled to a dual cell linear ion trap mass spectrometry. , 2014, Journal of chromatography. A.

[5]  Jimmy Lin,et al.  Cancer proteomics: developments in technology, clinical use and commercialization , 2015, Expert review of proteomics.

[6]  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 , 2013, Journal of Clinical Immunology.

[7]  The Uniprot Consortium,et al.  UniProt: a hub for protein information , 2014, Nucleic Acids Res..

[8]  S. Durham,et al.  Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. , 2006, Journal of Allergy and Clinical Immunology.

[9]  M. Gajhede,et al.  Dominating IgE-Binding Epitope of Bet v 1, the Major Allergen of Birch Pollen, Characterized by X-ray Crystallography and Site-Directed Mutagenesis , 2003, The Journal of Immunology.

[10]  T. Casale,et al.  Surveying the new Allergic and hypersensitivity conditions chapter of the International Classification of Diseases (ICD)‐11 , 2016, Allergy.

[11]  S. Durham,et al.  Functional rather than immunoreactive levels of IgG4 correlate closely with clinical response to grass pollen immunotherapy , 2012, Allergy.

[12]  S. Durham,et al.  Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. , 2006, The Journal of allergy and clinical immunology.

[13]  R. Van Ree,et al.  Quadrupole time-of-flight mass spectrometry: a method to study the actual expression of allergen isoforms identified by PCR cloning. , 2002, The Journal of allergy and clinical immunology.

[14]  M. Chapman,et al.  Epitope mapping of two major inhalant allergens, Der p I and Der f I, from mites of the genus Dermatophagoides. , 1987, Journal of immunology.

[15]  F. Altmann,et al.  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. , 2000, Analytical biochemistry.

[16]  H. R. Anderson,et al.  Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three , 2009, Allergy.

[17]  H. Niall Automated Edman degradation: the protein sequenator. , 1973, Methods in enzymology.

[18]  J. Bousquet,et al.  Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip. , 2014, Methods.

[19]  A. Louise,et al.  A regulatory dendritic cell signature correlates with the clinical efficacy of allergen-specific sublingual immunotherapy. , 2012, The Journal of allergy and clinical immunology.

[20]  R. Valenta,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. , 1993, Journal of immunology.

[21]  Ciara K O'Sullivan,et al.  Ultrasensitive aptamer based detection of β-conglutin food allergen. , 2014, Food chemistry.

[22]  Yu-Fang Jin,et al.  Transformative Impact of Proteomics on Cardiovascular Health and Disease: A Scientific Statement From the American Heart Association , 2015, Circulation.

[23]  R. Moritz,et al.  Structural studies on the allergen Der p1 from the house dust mite Dermatophagoides pteronyssinus: similarity with cysteine proteinases. , 1989, Protein sequences & data analysis.

[24]  P. Moingeon,et al.  Identification of Novel Short Ragweed Pollen Allergens Using Combined Transcriptomic and Immunoproteomic Approaches , 2015, PloS one.

[25]  H. Løwenstein,et al.  Quantitative Immunoelectrophoretic Methods as a Tool for the Analysis and Isolation of Allergens , 1978 .

[26]  T. Casale,et al.  Clinical efficacy of 300IR 5-grass pollen sublingual tablet in a US study: the importance of allergen-specific serum IgE. , 2012, The Journal of allergy and clinical immunology.

[27]  H. Malling,et al.  Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. , 2007, The Journal of allergy and clinical immunology.

[28]  V. Özenci,et al.  Rapid identification of bacteria from positive blood culture bottles by MALDI-TOF MS following short-term incubation on solid media. , 2015, Journal of medical microbiology.

[29]  F. Chew,et al.  NMR Structure and IgE Epitopes of Blo t 21, a Major Dust Mite Allergen from Blomia tropicalis* , 2012, The Journal of Biological Chemistry.

[30]  K. Ogura,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. , 2005, Journal of biochemistry.

[31]  M. Hornshaw,et al.  Absolute quantification of allergens from complex mixtures: a new sensitive tool for standardization of allergen extracts for specific immunotherapy. , 2011, Journal of proteome research.

[32]  R. Arnon,et al.  Structural basis of antigenic specificity and design of new vaccines , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  Julie Snow,et al.  How to Proceed , 2015 .

[34]  M. Calderón,et al.  An evidence-based appraisal of the surrogate markers of efficacy of allergen immunotherapy , 2011, Current opinion in allergy and clinical immunology.

[35]  H. Malling,et al.  Clinical efficacy of sublingual and subcutaneous birch pollen allergen‐specific immunotherapy: a randomized, placebo‐controlled, double‐blind, double‐dummy study , 2004, Allergy.

[36]  A. Dell,et al.  Differential immunogenicity and allergenicity of native and recombinant human lactoferrins: Role of glycosylation , 2013, European journal of immunology.

[37]  D. Coote,et al.  Evaluation of a capsulated hydrophilic carrier polymer (the ImmunoCAP) for measurement of specific IgE antibodies , 1990, Allergy.

[38]  S. Krause,et al.  Detection and structural characterization of natural Ara h 7, the third peanut allergen of the 2S albumin family. , 2010, Journal of proteome research.

[39]  R. Aalberse Clinical relevance of carbohydrate allergen epitopes , 1998, Allergy.

[40]  M. van den Berg,et al.  IgE epitopes on the cat (Felis domesticus) major allergen Fel d I: a study with overlapping synthetic peptides. , 1994, The Journal of allergy and clinical immunology.

[41]  F. Palmisano,et al.  Identification of allergenic milk proteins markers in fined white wines by capillary liquid chromatography-electrospray ionization-tandem mass spectrometry. , 2010, Journal of chromatography. A.

[42]  M. Shamji,et al.  Predictive biomarkers of clinical efficacy of allergen-specific immunotherapy: how to proceed. , 2013, Immunotherapy.

[43]  L. Klimek,et al.  New opportunities for allergen immunotherapy using synthetic peptide immuno-regulatory epitopes (SPIREs) , 2016, Expert review of clinical immunology.

[44]  D. DeMets,et al.  Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework , 2001, Clinical pharmacology and therapeutics.

[45]  Y. Wang,et al.  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 , 2014, PloS one.

[46]  D. Postma,et al.  Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story , 2016, Allergy.

[47]  S. Durham,et al.  Effect of grass pollen immunotherapy with Alutard SQ® on quality of life in seasonal allergic rhinoconjunctivitis , 2007, Allergy.

[48]  Ravi V. Kolla,et al.  Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals , 2013, Proceedings of the National Academy of Sciences.

[49]  H. Løwenstein Quantitative immunoelectrophoretic methods as a tool for the analysis and isolation of allergens. , 1978, Progress in allergy.

[50]  P. Briza,et al.  Standardization of allergen products: 2. Detailed characterization of GMP‐produced recombinant Phl p 5.0109 as European Pharmacopoeia reference standard , 2016, Allergy.

[51]  P. Moingeon,et al.  Identification of the cysteine protease Amb a 11 as a novel major allergen from short ragweed. , 2015, The Journal of allergy and clinical immunology.

[52]  M. Villalba,et al.  Cross-reactivity between the major allergen from olive pollen and unrelated glycoproteins: evidence of an epitope in the glycan moiety of the allergen. , 1996, The Journal of allergy and clinical immunology.

[53]  S. Spector,et al.  Allergen immunotherapy: a practice parameter third update. , 2007, The Journal of allergy and clinical immunology.

[54]  W. Minor,et al.  Molecular Determinants for Antibody Binding on Group 1 House Dust Mite Allergens* , 2011, The Journal of Biological Chemistry.

[55]  R. Esch,et al.  Immunotherapy Preparation Guidelines, Rules, and Regulation , 2013, Current Allergy and Asthma Reports.

[56]  F. Felici,et al.  Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen , 2013, Proceedings of the National Academy of Sciences.

[57]  S. Vieths,et al.  High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phl p 2 As Revealed by X-Ray Crystallography1 , 2009, The Journal of Immunology.

[58]  M. Pallardy,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. , 2016, The Journal of allergy and clinical immunology.

[59]  F. Chew,et al.  Patterns of IgE sensitization in house dust mite‐allergic patients: implications for allergen immunotherapy , 2016, Allergy.

[60]  Dong-Gi Lee,et al.  Quantitation of soybean allergens using tandem mass spectrometry. , 2011, Journal of proteome research.

[61]  Ahmed Gomaa,et al.  Simultaneous detection of multi-allergens in an incurred food matrix using ELISA, multiplex flow cytometry and liquid chromatography mass spectrometry (LC-MS). , 2015, Food chemistry.

[62]  K. Hoffmann‐Sommergruber,et al.  Isoforms of Bet v 1, the Major Birch Pollen Allergen, Analyzed by Liquid Chromatography, Mass Spectrometry, and cDNA Cloning (*) , 1995, The Journal of Biological Chemistry.

[63]  Uwe Christians,et al.  Liquid chromatography and mass spectrometry in food allergen detection. , 2011, Journal of food protection.

[64]  Steve L Taylor,et al.  Mass spectrometric analysis of allergens in roasted walnuts. , 2016, Journal of proteomics.

[65]  J. Greenbaum,et al.  T-cell epitope conservation across allergen species is a major determinant of immunogenicity. , 2016, The Journal of allergy and clinical immunology.

[66]  C. Mohan,et al.  Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity? , 2015, BMJ : British Medical Journal.

[67]  P. Moingeon Biomarkers for Allergen Immunotherapy: A "Panoromic" View. , 2016, Immunology and allergy clinics of North America.

[68]  H. Niall [36] Automated edman degradation: The protein sequenator , 1973 .

[69]  P. Blumberg,et al.  Absolute quantitation of endogenous proteins with precision and accuracy using a capillary Western system. , 2013, Analytical biochemistry.

[70]  J. McGready,et al.  Performance and Pain Tolerability of Current Diagnostic Allergy Skin Prick Test Devices. , 2015, The journal of allergy and clinical immunology. In practice.

[71]  P. Devillier,et al.  Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. , 2009, The Journal of allergy and clinical immunology.

[72]  A. Sheikh,et al.  EAACI: A European Declaration on Immunotherapy. Designing the future of allergen specific immunotherapy , 2012, Clinical and Translational Allergy.

[73]  Mark R. Trusheim,et al.  Stratified medicine: strategic and economic implications of combining drugs and clinical biomarkers , 2007, Nature Reviews Drug Discovery.

[74]  P. Roepstorff,et al.  Determination of Isoforms, N-Linked Glycan Structure and Disulfide Bond Linkages of the Major Cat Allergen Fel d1 by a Mass Spectrometric Approach , 1997, Biological chemistry.

[75]  R. Ree The create project: EU support for the improvement of allergen standardization in Europe , 2004 .

[76]  S. Vieths,et al.  Standardization of allergen products: 3. Validation of candidate European Pharmacopoeia standard methods for quantification of major birch allergen Bet v 1 , 2016, Allergy.

[77]  J. J. Robinson,et al.  Biomolecular characterization of allergenic proteins in snow crab (Chionoecetes opilio) and de novo sequencing of the second allergen arginine kinase using tandem mass spectrometry. , 2011, Journal of proteomics.

[78]  Qian Zhang,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. , 2011, Analytical chemistry.

[79]  E. Meltzer,et al.  The prevalence of nasal symptoms attributed to allergies in the United States: findings from the burden of rhinitis in an America survey. , 2008, Allergy and asthma proceedings.

[80]  F. Spertini,et al.  Api m 6: a new bee venom allergen. , 2001, The Journal of allergy and clinical immunology.

[81]  R. Rustandi,et al.  Automated capillary Western dot blot method for the identity of a 15-valent pneumococcal conjugate vaccine. , 2015, Analytical biochemistry.

[82]  S. Wenzel,et al.  Asthma outcomes: biomarkers. , 2012, The Journal of allergy and clinical immunology.

[83]  P. Matricardi,et al.  Rhinitis , sinusitis , and upper airway disease The effect of component-resolved diagnosis on specific immunotherapy prescription in children with hay fever , 2022 .

[84]  Gerald M Rubin,et al.  Defining the mandate of proteomics in the post-genomics era: workshop report. , 2002, Molecular & cellular proteomics : MCP.

[85]  J. Lay,et al.  Rapid identification of bacteria based on spectral patterns using MALDI-TOFMS. , 2000, Methods in molecular biology.

[86]  Graham M Lord,et al.  Immune biomarkers: the promises and pitfalls of personalized medicine , 2015, Nature Reviews Immunology.

[87]  R. Kumar,et al.  The Prevalence, Severity, and Distribution of Childhood Food Allergy in the United States , 2011, Pediatrics.

[88]  Stephan Seifert,et al.  Matrix-assisted laser desorption/ionization mass spectrometric investigation of pollen and their classification by multivariate statistics. , 2012, Rapid communications in mass spectrometry : RCM.

[89]  C. Radauer,et al.  Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences , 2014, Allergy.

[90]  Massimo Natale,et al.  Cow's milk allergens identification by two-dimensional immunoblotting and mass spectrometry. , 2004, Molecular nutrition & food research.

[91]  S. Durham,et al.  Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. , 2008, The Journal of allergy and clinical immunology.

[92]  S. Paczesny Discovery and validation of graft-versus-host disease biomarkers. , 2011, Blood.

[93]  K. Meno Allergen structures and epitopes , 2011, Allergy.

[94]  M. Ernst,et al.  Phl p 3: Structural and immunological characterization of a major allergen of timothy grass pollen , 2006, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[95]  Dean Clarke,et al.  Next generation of food allergen quantification using mass spectrometric systems. , 2014, Journal of proteome research.

[96]  C. López-Otín,et al.  The amino acid sequence of Ole e I, the major allergen from olive tree (Olea europaea) pollen. , 1993, European journal of biochemistry.

[97]  A. Luxen,et al.  Activation Mechanism of Recombinant Der p 3 Allergen Zymogen , 2008, Journal of Biological Chemistry.

[98]  L. Elviri,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 , 2007, Analytical and bioanalytical chemistry.

[99]  R. Valenta,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 , 2011, The Journal of Immunology.

[100]  R. Van Ree,et al.  Standardization of allergen products: 1. Detailed characterization of GMP‐produced recombinant Bet v 1.0101 as biological reference preparation , 2009, Allergy.

[101]  Scott H Sicherer,et al.  Clinical reviews in allergy and immunology , 2022 .

[102]  A. Roussel,et al.  Development and evaluation of a sublingual tablet based on recombinant Bet v 1 in birch pollen‐allergic patients , 2015, Allergy.

[103]  S. Tuske,et al.  Epitope mapping by amide hydrogen/deuterium exchange coupled with immobilization of antibody, on-line proteolysis, liquid chromatography and mass spectrometry. , 2009, Rapid communications in mass spectrometry : RCM.

[104]  Damian J. Houde,et al.  Conformational analysis of recombinant monoclonal antibodies with hydrogen/deuterium exchange mass spectrometry. , 2013, Methods in molecular biology.

[105]  Andrew N Hoofnagle,et al.  The fundamental flaws of immunoassays and potential solutions using tandem mass spectrometry. , 2009, Journal of immunological methods.

[106]  K. Ruxrungtham,et al.  The House Dust Mite Major Allergen Der p 23 Displays O-Glycan-Independent IgE Reactivities but No Chitin-Binding Activity , 2016, International Archives of Allergy and Immunology.

[107]  T. Platts-Mills,et al.  Drug allergens and food--the cetuximab and galactose-α-1,3-galactose story. , 2014, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[108]  P. Moingeon Update on immune mechanisms associated with sublingual immunotherapy: practical implications for the clinician. , 2013, The journal of allergy and clinical immunology. In practice.

[109]  H. Malling,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 , 2014, Clinical and Translational Allergy.

[110]  E. Ezan,et al.  Mass spectrometric investigation of molecular variability of grass pollen group 1 allergens. , 2009, Journal of proteome research.

[111]  W. Minor,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. , 2009, Journal of molecular biology.

[112]  A. Ponsonby,et al.  Food , drug , insect sting allergy , and anaphylaxis Skin prick test responses and allergen-specific IgE levels as predictors of peanut , egg , and sesame allergy in infants , 2022 .

[113]  H. Bennich,et al.  Immunoglobulin E. A new class of human immunoglobulin. , 1968, Journal of Immunology.