Acknowledgments
We thank Tomas Barker-Tejeda for the critical reading of the manuscript.
Figure Legends
Figure 1: Diagnostic algorithm and decision tree for AIT using CRD in
Grass pollen allergy. Grass pollen allergy is one of the most studied
allergy models. Major allergen sensitization is required before
considering AIT. The combination of major allergens and pan-allergens
provides the necessary tools for AIT decisions. Profilin allergy, might
be a contraindication only in severe food allergic patients, while
double sensitization to both pan-allergens is associated to many years
of disease evolution, poly-sensitization and poor intervention outcome
Figure 2: Diagnostic algorithm and decision tree for AIT using CRD in
Olive pollen allergy. Olive pollen allergies is one of the most complex
allergy models. Usually olive cultivars cover homogeneous areas and
present acute differences in allergen pollen content. In dense pollen
areas, patients are exposed to the highest pollen counts recorded. Th
existing of complex profiles, marked by minor allergens sensitization,
makes CRD a fundamental tool for patient management and AIT decissions.
Figure 3: Diagnostic algorithm and decision tree for AIT using CRD in
nsLTPs mediated allergies. The existence of cross-reactivity between
nsLPTs from Artemisia and Platanus pollens, makes CRD
necessary. LTP immunotherapy with an enriched Pru p 3 can be considered
in Countries with availability of this type of therapy
Figure 4: Diagnostic algorithm for in vitro diagnostics and Decision
tree for AIT using CRD in pollen allergies. Discrimination of primary
sensitizers and pan-allergens positivity is needed. AIT guidelines do
not recommend AIT for poly-sensitized patients
Figure 5: Diagnostic algorithm for in vitro diagnostics in epithelia
allergy and associated decision tree for AIT using CRD. The proposed
algorithm discriminates between primary sensitization and cross-reactive
sIgE response. Only patients sensitized to major allergens should be
eligible for AIT.
Figure 6: Established discriminating and cross-reactive allergens of
HBV, YJV and PDV. While allergens are identified that enable a
differentiation between HBV (Api m 1, Api m 3, Api m 4 and Api m 10) and
YJV/PDV (Ves v 1/Pold 1 and Ves v 5/Pol d 5) sensitization, the so far
known allergens of YJV and PDV exhibit cross-reactivity.
Figure 7: Diagnostic algorithm for in vitro diagnostics of (A) HBV and
YJV allergy and (B) YJV and PDV allergy. The diagnostic algorithm shown
in (A), with the corresponding PDV allergens Pol d 1 and Pol d 5 can
also be used to discriminate between HBV and PDV allergy. In addition,
to discriminate in the case of double-positive test results, CRD might
also be useful in cases of negative results despite a convincing history
of venom allergy or in cases of discrepancies between history, skin
tests and venom extract-based testing. A plus indicates a positive and a
minus a negative test result. Of note, the allergens Api m 4 and Pol d 1
(in brackets) are only available for selected multiplex sIgE test
platforms. *The allergens Api m 2 and Api m 5 are potentially
cross-reactive with their homologues from YJV and PDV (not available for
CRD) and, hence, a positive test results does not necessarily exclude
allergy to vespid venom.
Figure 8: Diagnostic algorithm for in vitro diagnostics in peanut
allergy oriented to make POIT decision. Discriminant analysis between
storage allergens and cross-reactive to pollen and nsLTPs is proposed.
Only patients with positive sIgE to any of the Ara h 1,2,3,6 should be
eligible for POIT.
BOXES:
MAJOR MILESTONES:
- IgE Discovery (1968)
- First commercial reagents for specific IgE (1973)
- Knowledge and Characterization of the most relevant allergens
(1985-2005)
- Development of multiplexed allergens: 1999
- Handbook of Molecular Allergology: 2016
- Progressive use in clinical practice of CRD: 2010-2021
- Progressive understanding of AIT mechanisms: 2010-2021
- First AIT product registered following Pharmaceutical development
guidelines: 2007
- First OIT for peanut allergy registered: 2020
FUTURE RESEARCH PERSPECTIVES:
- Affinity and avidity need to be explored in IgE response to allergens
- T-cell reactivity to allergens is a critical parameter
- Combination of new biologics and AIT and associated diagnosis will
open new intervention strategies
- New regulation of in vitro diagnostics will increase the quality of
CRD , but might limmit innovation and available molecules
REFERENCES
1. Bonertz A, Roberts GC, Hoefnagel M,
et al. Challenges in the implementation of EAACI guidelines on allergen
immunotherapy: A global perspective on the regulation of allergen
products. Allergy. 2018;73(1):64-76.
2. Bonertz A, Roberts G, Slater JE, et
al. Allergen manufacturing and quality aspects for allergen
immunotherapy in Europe and the United States: An analysis from the
EAACI AIT Guidelines Project. Allergy. 2018;73(4):816-826.
3. van Ree R, Chapman MD, Ferreira F,
et al. The CREATE project: development of certified reference materials
for allergenic products and validation of methods for their
quantification. Allergy. 2008;63(3):310-326.
4. Matricardi PM, Kleine-Tebbe J,
Hoffmann HJ, et al. EAACI Molecular Allergology User’s Guide.Pediatr Allergy Immunol. 2016;27 Suppl 23:1-250.
5. Barker-Tejeda TC, Bazire R, Obeso
D, et al. Exploring novel systemic biomarker approaches in grass-pollen
sublingual immunotherapy using omics. Allergy. 2020.
6. Sokolowska M, Boonpiyathad T,
Escribese MM, Barber D. Allergen-specific immunotherapy: Power of
adjuvants and novel predictive biomarkers. Allergy.2019;74(11):2061-2063.
7. Barber D, Villasenor A, Escribese
MM. Metabolomics strategies to discover new biomarkers associated to
severe allergic phenotypes. Asia Pac Allergy. 2019;9(4):e37.
8. Sanchez-Solares J, Delgado-Dolset
MI, Mera-Berriatua L, et al. Respiratory allergies with no associated
food allergy disrupt oral mucosa integrity. Allergy.2019;74(11):2261-2265.
9. Obeso D, Mera-Berriatua L,
Rodriguez-Coira J, et al. Multi-omics analysis points to altered
platelet functions in severe food-associated respiratory allergy.Allergy. 2018;73(11):2137-2149.
10. Rosace D, Gomez-Casado C,
Fernandez P, et al. Profilin-mediated food-induced allergic reactions
are associated with oral epithelial remodeling. J Allergy Clin
Immunol. 2019;143(2):681-690 e681.
11. Eguiluz-Gracia I, Tay TR, Hew M,
et al. Recent developments and highlights in biomarkers in allergic
diseases and asthma. Allergy. 2018;73(12):2290-2305.
12. Barber D, Rico P, Blanco C,
Fernandez-Rivas M, Ibanez MD, Escribese MM. GRAZAX(R): a sublingual
immunotherapy vaccine for Hay fever treatment: from concept to
commercialization. Hum Vaccin Immunother. 2019;15(12):2887-2895.
13. Varona R, Ramos T, Escribese MM,
et al. Persistent regulatory T-cell response 2 years after 3 years of
grass tablet SLIT: Links to reduced eosinophil counts, sIgE levels, and
clinical benefit. Allergy. 2019;74(2):349-360.
14. Suarez-Fueyo A, Ramos T, Galan A,
et al. Grass tablet sublingual immunotherapy downregulates the TH2
cytokine response followed by regulatory T-cell generation. J
Allergy Clin Immunol. 2014;133(1):130-138 e131-132.
15. van de Veen W, Akdis M. Tolerance
mechanisms of allergen immunotherapy. Allergy.2020;75(5):1017-1018.
16. Satitsuksanoa P, van de Veen W,
Akdis M. B-cell responses in allergen immunotherapy. Curr Opin
Allergy Clin Immunol. 2019;19(6):632-639.
17. Jansen K, Cevhertas L, Ma S,
Satitsuksanoa P, Akdis M, van de Veen W. Regulatory B cells, A to Z.Allergy. 2021.
18. Ma S, Satitsuksanoa P, Jansen K,
Cevhertas L, van de Veen W, Akdis M. B regulatory cells in allergy.Immunol Rev. 2021;299(1):10-30.
19. Eljaszewicz A, Ruchti F,
Radzikowska U, et al. Trained immunity and tolerance in innate lymphoid
cells, monocytes, and dendritic cells during allergen-specific
immunotherapy. J Allergy Clin Immunol. 2020.
20. A WAO - ARIA - GA(2)LEN consensus
document on molecular-based allergy diagnosis (PAMD@): Update 2020.World Allergy Organ J. 2020;13(2):100091.
21. Goodman RE, Breiteneder H. The
WHO/IUIS Allergen Nomenclature. Allergy. 2019;74(3):429-431.
22. Costa J, Bavaro SL, Benede S, et
al. Are Physicochemical Properties Shaping the Allergenic Potency of
Plant Allergens? Clin Rev Allergy Immunol. 2020.
23. Costa J, Villa C, Verhoeckx K, et
al. Are Physicochemical Properties Shaping the Allergenic Potency of
Animal Allergens? Clin Rev Allergy Immunol. 2021.
24. Kaul S, Zimmer J, Dehus O, et al.
Validation of ELISA methods for quantification of the major birch
allergen Bet v 1 (BSP090). Pharmeur Bio Sci Notes.2017;2017:69-87.
25. Kaul S, Zimmer J, Dehus O, 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;71(10):1414-1424.
26. Vieths S, Barber D, Chapman M, et
al. Establishment of recombinant major allergens Bet v 1 and Phl p 5a as
Ph. Eur. reference standards and validation of ELISA methods for their
measurement. Results from feasibility studies. Pharmeur Bio Sci
Notes. 2012;2012:118-134.
27. Nolte M, Barber D, Maloney J, et
al. Timothy specific IgE levels are associated with efficacy and safety
of timothy grass sublingual immunotherapy tablet. Ann Allergy
Asthma Immunol. 2015;115(6):509-515 e502.
28. Duffort O, Palomares O,
Lombardero M, et al. Variability of Ole e 9 allergen in olive pollen
extracts: relevance of minor allergens in immunotherapy treatments.Int Arch Allergy Immunol. 2006;140(2):131-138.
29. Barber D, Moreno C, Ledesma A, et
al. Degree of olive pollen exposure and sensitization patterns. Clinical
implications. J Investig Allergol Clin Immunol. 2007;17 Suppl
1:11-16.
30. Hatzler L, Panetta V, Lau S, et
al. Molecular spreading and predictive value of preclinical IgE response
to Phleum pratense in children with hay fever. J Allergy Clin
Immunol. 2012;130(4):894-901 e895.
31. Posa D, Perna S, Resch Y, et al.
Evolution and predictive value of IgE responses toward a comprehensive
panel of house dust mite allergens during the first 2 decades of life.J Allergy Clin Immunol. 2017;139(2):541-549 e548.
32. Custovic A, Sonntag HJ, Buchan
IE, Belgrave D, Simpson A, Prosperi MCF. Evolution pathways of IgE
responses to grass and mite allergens throughout childhood. J
Allergy Clin Immunol. 2015;136(6):1645-1652 e1648.
33. Matricardi PM. Allergen-specific
immunoprophylaxis: toward secondary prevention of allergic rhinitis?Pediatr Allergy Immunol. 2014;25(1):15-18.
34. Lund G, Brand S, Ramos T, et al.
Strong and frequent T-cell responses to the minor allergen Phl p 12 in
Spanish patients IgE-sensitized to Profilins. Allergy.2018;73(5):1013-1021.
35. Barber D, de la Torre F, Feo F,
et al. Understanding patient sensitization profiles in complex pollen
areas: a molecular epidemiological study. Allergy.2008;63(11):1550-1558.
36. Barber D, de la Torre F,
Lombardero M, et al. Component-resolved diagnosis of pollen allergy
based on skin testing with profilin, polcalcin and lipid transfer
protein pan-allergens. Clin Exp Allergy. 2009;39(11):1764-1773.
37. Cipriani F, Mastrorilli C,
Tripodi S, et al. Diagnostic relevance of IgE sensitization profiles to
eight recombinant Phleum pratense molecules. Allergy.2018;73(3):673-682.
38. Hernandez-Ramirez G, Pazos-Castro
D, Gomez Torrijos E, et al. Group 1 allergens, transported by mold
spores, induce asthma exacerbation in a mouse model. Allergy.2020;75(9):2388-2391.
39. Asero R, Monsalve R, Barber D.
Profilin sensitization detected in the office by skin prick test: a
study of prevalence and clinical relevance of profilin as a plant food
allergen. Clin Exp Allergy. 2008;38(6):1033-1037.
40. Ruiz-Garcia M, Garcia Del Potro
M, Fernandez-Nieto M, Barber D, Jimeno-Nogales L, Sastre J. Profilin: a
relevant aeroallergen? J Allergy Clin Immunol.2011;128(2):416-418.
41. Alvarado MI, Jimeno L, De La
Torre F, et al. Profilin as a severe food allergen in allergic patients
overexposed to grass pollen. Allergy. 2014;69(12):1610-1616.
42. Rodriguez Del Rio P, Diaz-Perales
A, Sanchez-Garcia S, et al. Profilin, a Change in the Paradigm. J
Investig Allergol Clin Immunol. 2018;28(1):1-12.
43. Matricardi PM. IgE to
cross-reactive carbohydrate determinants: Origins, functions, and
confounding role in nPhl p 4-IgE assays. J Allergy Clin Immunol.2020;145(6):1554-1555.
44. Salcedo G, Sanchez-Monge R,
Barber D, Diaz-Perales A. Plant non-specific lipid transfer proteins: an
interface between plant defence and human allergy. Biochim Biophys
Acta. 2007;1771(6):781-791.
45. Skypala IJ, Bartra J, Ebo DG, et
al. The diagnosis and management of allergic reactions in patients
sensitized to non-specific Lipid Transfer Proteins. Allergy.2021.
46. Fernandez-Rivas M, Garrido
Fernandez S, Nadal JA, et al. Randomized double-blind,
placebo-controlled trial of sublingual immunotherapy with a Pru p 3
quantified peach extract. Allergy. 2009;64(6):876-883.
47. Gomez F, Bogas G, Gonzalez M, et
al. The clinical and immunological effects of Pru p 3 sublingual
immunotherapy on peach and peanut allergy in patients with systemic
reactions. Clin Exp Allergy. 2017;47(3):339-350.
48. Palomares F, Gomez F, Bogas G, et
al. Immunological Changes Induced in Peach Allergy Patients with
Systemic Reactions by Pru p 3 Sublingual Immunotherapy. Mol Nutr
Food Res. 2018;62(3).
49. Biedermann T, Winther L, Till SJ,
Panzner P, Knulst A, Valovirta E. Birch pollen allergy in Europe.Allergy. 2019;74(7):1237-1248.
50. Biedermann T, Kuna P, Panzner P,
et al. The SQ tree SLIT-tablet is highly effective and well tolerated:
Results from a randomized, double-blind, placebo-controlled phase III
trial. J Allergy Clin Immunol. 2019;143(3):1058-1066 e1056.
51. Nolte H, Waserman S, Ellis AK,
Biedermann T, Wurtzen PA. Treatment Effect of the Tree Pollen
SLIT-Tablet on Allergic Rhinoconjunctivitis During Oak Pollen Season.J Allergy Clin Immunol Pract. 2021.
52. Wurtzen PA, Gronager PM, Lund G,
et al. Simplified AIT for allergy to several tree pollens-Arguments from
the immune outcome analyses following treatment with SQ tree
SLIT-tablet. Clin Exp Allergy. 2021;51(2):284-295.
53. van der Valk JPM, Nagl B, van
Wljk RG, Bohle B, de Jong NW. The Effect of Birch Pollen Immunotherapy
on Apple and rMal d 1 Challenges in Adults with Apple Allergy.Nutrients. 2020;12(2).
54. Till SJ, Stage BS, Skypala I,
Biedermann T. Potential treatment effect of the SQ tree SLIT-tablet on
pollen food syndrome caused by apple. Allergy.2020;75(8):2059-2061.
55. Sanchez Acosta G, Kinaciyan T,
Kitzmuller C, Mobs C, Pfutzner W, Bohle B. IgE-blocking antibodies
following SLIT with recombinant Mal d 1 accord with improved apple
allergy. J Allergy Clin Immunol. 2020;146(4):894-900 e892.
56. Okamoto Y, Okubo K, Yonekura S,
et al. Efficacy and safety of sublingual immunotherapy for two seasons
in patients with Japanese cedar pollinosis. Int Arch Allergy
Immunol. 2015;166(3):177-188.
57. Gotoh M, Yonekura S, Imai T, et
al. Long-Term Efficacy and Dose-Finding Trial of Japanese Cedar Pollen
Sublingual Immunotherapy Tablet. J Allergy Clin Immunol Pract.2019;7(4):1287-1297 e1288.
58. Alvaro-Lozano M, Akdis CA, Akdis
M, et al. EAACI Allergen Immunotherapy User’s Guide. Pediatr
Allergy Immunol. 2020;31 Suppl 25:1-101.
59. Christensen LH, Ipsen H, Nolte H,
et al. Short ragweeds is highly cross-reactive with other ragweeds.Ann Allergy Asthma Immunol. 2015;115(6):490-495 e491.
60. Creticos PS, Maloney J, Bernstein
DI, et al. Randomized controlled trial of a ragweed allergy
immunotherapy tablet in North American and European adults. J
Allergy Clin Immunol. 2013;131(5):1342-1349 e1346.
61. Nolte H, Bernstein DI, Nelson HS,
Ellis AK, Kleine-Tebbe J, Lu S. Efficacy and Safety of Ragweed
SLIT-Tablet in Children with Allergic Rhinoconjunctivitis in a
Randomized, Placebo-Controlled Trial. J Allergy Clin Immunol
Pract. 2020;8(7):2322-2331 e2325.
62. Uriarte SA, Sastre J. Clinical
relevance of molecular diagnosis in pet allergy. Allergy.2016;71(7):1066-1068.
63. Ukleja-Sokolowska N,
Gawronska-Ukleja E, Zbikowska-Gotz M, et al. Analysis of feline and
canine allergen components in patients sensitized to pets. Allergy
Asthma Clin Immunol. 2016;12:61.
64. Nordlund B, Konradsen JR, Kull I,
et al. IgE antibodies to animal-derived lipocalin, kallikrein and
secretoglobin are markers of bronchial inflammation in severe childhood
asthma. Allergy. 2012;67(5):661-669.
65. Schoos AM, Nwaru BI, Borres MP.
Component-resolved diagnostics in pet allergy: Current perspectives and
future directions. J Allergy Clin Immunol. 2021.
66. Uriarte SA, Gronlund H,
Wintersand A, Bronge J, Sastre J. Clinical and immunologic changes due
to subcutaneous immunotherapy with cat and dog extracts using an
ultrarush up-dosing phase: a real-life study. J Investig Allergol
Clin Immunol. 2020:0.
67. Asarnoj A, Hamsten C, Waden K, et
al. Sensitization to cat and dog allergen molecules in childhood and
prediction of symptoms of cat and dog allergy in adolescence: A
BAMSE/MeDALL study. J Allergy Clin Immunol. 2016;137(3):813-821
e817.
68. Nanda A, O’Connor M, Anand M, et
al. Dose dependence and time course of the immunologic response to
administration of standardized cat allergen extract. J Allergy
Clin Immunol. 2004;114(6):1339-1344.
69. Wintersand A, Asplund K, Binnmyr
J, et al. Allergens in dog extracts: Implication for diagnosis and
treatment. Allergy. 2019;74(8):1472-1479.
70. Lent AM, Harbeck R, Strand M, et
al. Immunologic response to administration of standardized dog allergen
extract at differing doses. J Allergy Clin Immunol.2006;118(6):1249-1256.
71. Uriarte SA, Sastre J.
Subcutaneous Immunotherapy With High-Dose Cat and Dog Extracts: A
Real-life Study. J Investig Allergol Clin Immunol.2020;30(3):169-174.
72. Uriarte S, Sastre J. Safety of an
Ultrarush (4 Hours) Subcutaneous Immunotherapy Schedule With Cat and Dog
Extracts Using an Infusion Pump. J Investig Allergol Clin
Immunol. 2018;28(6):430-432.
73. Barber D, Arias J, Boquete M, et
al. Analysis of mite allergic patients in a diverse territory by
improved diagnostic tools. Clin Exp Allergy.2012;42(7):1129-1138.
74. Celi G, Brusca I, Scala E, et al.
House dust mite allergy in Italy-Diagnostic and clinical relevance of
Der p 23 (and of minor allergens): A real-life, multicenter study.Allergy. 2019;74(9):1787-1789.
75. Arias-Irigoyen J, Lombardero M,
Arteaga C, Carpizo JA, Barber D. Limited IgE cross-reactivity between
Dermatophagoides pteronyssinus and Glycyphagus domesticus in patients
naturally exposed to both mite species. J Allergy Clin Immunol.2007;120(1):98-104.
76. Blanco C, Quiralte J, Castillo R,
et al. Anaphylaxis after ingestion of wheat flour contaminated with
mites. J Allergy Clin Immunol. 1997;99(3):308-313.
77. Arroabarren E, Echechipia S,
Galbete A, Lizaso MT, Olaguibel JM, Tabar AI. Association Between
Component-Resolved Diagnosis of House Dust Mite Allergy and Efficacy and
Safety of Specific Immunotherapy. J Investig Allergol Clin
Immunol. 2019;29(2):164-167.
78. Rodriguez-Dominguez A, Berings M,
Rohrbach A, et al. Molecular profiling of allergen-specific antibody
responses may enhance success of specific immunotherapy. J Allergy
Clin Immunol. 2020;146(5):1097-1108.
79. Tripodi S, Frediani T, Lucarelli
S, et al. Molecular profiles of IgE to Phleum pratense in children with
grass pollen allergy: implications for specific immunotherapy. J
Allergy Clin Immunol. 2012;129(3):834-839 e838.
80. Insights into social insects from
the genome of the honeybee Apis mellifera. Nature.2006;443(7114):931-949.
81. Honeybee Genome Sequencing C.
Insights into social insects from the genome of the honeybee Apis
mellifera. Nature. 2006;443(7114):931-949.
82. Peiren N, Vanrobaeys F, de Graaf
DC, Devreese B, Van Beeumen J, Jacobs FJ. The protein composition of
honeybee venom reconsidered by a proteomic approach. Biochim
Biophys Acta. 2005;1752(1):1-5.
83. Van Vaerenbergh M, Debyser G,
Devreese B, de Graaf DC. Exploring the hidden honeybee (Apis mellifera)
venom proteome by integrating a combinatorial peptide ligand library
approach with FTMS. J Proteomics. 2014;99:169-178.
84. Radauer C, Nandy A, Ferreira F,
et al. Update of the WHO/IUIS Allergen Nomenclature Database based on
analysis of allergen sequences. Allergy. 2014;69(4):413-419.
85. Spillner E, Blank S, Jakob T.
Hymenoptera allergens: from venom to ”venome”. Front Immunol.2014;5:77.
86. Frick M, Fischer J, Helbling A,
et al. Predominant Api m 10 sensitization as risk factor for treatment
failure in honey bee venom immunotherapy. The Journal of allergy
and clinical immunology. 2016;138(6):1663-1671 e1669.
87. Kohler J, Blank S, Muller S, et
al. Component resolution reveals additional major allergens in patients
with honeybee venom allergy. The Journal of allergy and clinical
immunology. 2014;133(5):1383-1389, 1389 e1381-1386.
88. Blank S, Bantleon FI, McIntyre M,
Ollert M, Spillner E. The major royal jelly proteins 8 and 9 (Api m 11)
are glycosylated components of Apis mellifera venom with allergenic
potential beyond carbohydrate-based reactivity. Clinical and
experimental allergy : journal of the British Society for Allergy and
Clinical Immunology. 2012;42(6):976-985.
89. Blank S, Seismann H, McIntyre M,
et al. Vitellogenins are new high molecular weight components and
allergens (Api m 12 and Ves v 6) of Apis mellifera and Vespula vulgaris
venom. PloS one. 2013;8(4):e62009.
90. Michel Y, McIntyre M, Ginglinger
H, et al. The putative serine protease inhibitor Api m 6 from Apis
mellifera venom: recombinant and structural evaluation. J Investig
Allergol Clin Immunol. 2012;22(7):476-484.
91. Ruiz B, Serrano P, Verdu M,
Moreno C. Sensitization to Api m 1, Api m 2, and Api m 4: association
with safety of bee venom immunotherapy. Ann Allergy Asthma
Immunol. 2015;114(4):350-352.
92. King TP, Spangfort MD. Structure
and biology of stinging insect venom allergens. International
archives of allergy and immunology. 2000;123(2):99-106.
93. Muller UR. Recombinant
Hymenoptera venom allergens. Allergy. 2002;57(7):570-576.
94. Kolarich D, Leonard R, Hemmer W,
Altmann F. The N-glycans of yellow jacket venom hyaluronidases and the
protein sequence of its major isoform in Vespula vulgaris. FEBS
J. 2005;272(20):5182-5190.
95. Seismann H, Blank S, Braren I, et
al. Dissecting cross-reactivity in hymenoptera venom allergy by
circumvention of alpha-1,3-core fucosylation. Mol Immunol.2010;47(4):799-808.
96. Blank S, Seismann H, Bockisch B,
et al. Identification, recombinant expression, and characterization of
the 100 kDa high molecular weight Hymenoptera venom allergens Api m 5
and Ves v 3. Journal of immunology. 2010;184(9):5403-5413.
97. Cifuentes L, Vosseler S, Blank S,
et al. Identification of Hymenoptera venom-allergic patients with
negative specific IgE to venom extract by using recombinant allergens.The Journal of allergy and clinical immunology.2014;133(3):909-910.
98. Ebo DG, Faber M, Sabato V, Leysen
J, Bridts CH, De Clerck LS. Component-resolved diagnosis of wasp (yellow
jacket) venom allergy. Clinical and experimental allergy : journal
of the British Society for Allergy and Clinical Immunology.2013;43(2):255-261.
99. Korosec P, Valenta R, Mittermann
I, et al. High sensitivity of CAP-FEIA rVes v 5 and rVes v 1 for
diagnosis of Vespula venom allergy. The Journal of allergy and
clinical immunology. 2012;129(5):1406-1408.
100. Mittermann I, Zidarn M, Silar
M, et al. Recombinant allergen-based IgE testing to distinguish bee and
wasp allergy. The Journal of allergy and clinical immunology.2010;125(6):1300-1307 e1303.
101. Seismann H, Blank S, Cifuentes
L, et al. Recombinant phospholipase A1 (Ves v 1) from yellow jacket
venom for improved diagnosis of hymenoptera venom hypersensitivity.Clin Mol Allergy. 2010;8:7.
102. Vos B, Kohler J, Muller S,
Stretz E, Rueff F, Jakob T. Spiking venom with rVes v 5 improves
sensitivity of IgE detection in patients with allergy to Vespula venom.The Journal of allergy and clinical immunology.2013;131(4):1225-1227, 1227 e1221.
103. Hofmann SC, Pfender N,
Weckesser S, Huss-Marp J, Jakob T. Added value of IgE detection to rApi
m 1 and rVes v 5 in patients with Hymenoptera venom allergy. The
Journal of allergy and clinical immunology. 2011;127(1):265-267.
104. Muller UR, Johansen N, Petersen
AB, Fromberg-Nielsen J, Haeberli G. Hymenoptera venom allergy: analysis
of double positivity to honey bee and Vespula venom by estimation of IgE
antibodies to species-specific major allergens Api m1 and Ves v5.Allergy. 2009;64(4):543-548.
105. Jin C, Focke M, Leonard R,
Jarisch R, Altmann F, Hemmer W. Reassessing the role of hyaluronidase in
yellow jacket venom allergy. The Journal of allergy and clinical
immunology. 2010;125(1):184-190 e181.
106. Monsalve RI, Vega A, Marques L,
et al. Component-resolved diagnosis of vespid venom-allergic
individuals: phospholipases and antigen 5s are necessary to identify
Vespula or Polistes sensitization. Allergy. 2012;67(4):528-536.
107. Schiener M, Hilger C, Eberlein
B, et al. The high molecular weight dipeptidyl peptidase IV Pol d 3 is a
major allergen of Polistes dominula venom. Sci Rep.2018;8(1):1318.
108. Michel J, Brockow K, Darsow U,
et al. Added sensitivity of component-resolved diagnosis in hymenoptera
venom-allergic patients with elevated serum tryptase and/or
mastocytosis. Allergy. 2016;71(5):651-660.
109. Vickery BP, Vereda A, Casale
TB, et al. AR101 Oral Immunotherapy for Peanut Allergy. N Engl J
Med. 2018;379(21):1991-2001.
110. J OBH, Beyer K, Abbas A, et al.
Efficacy and safety of oral immunotherapy with AR101 in European
children with a peanut allergy (ARTEMIS): a multicentre, double-blind,
randomised, placebo-controlled phase 3 trial. Lancet Child Adolesc
Health. 2020;4(10):728-739.
111. Wang J. Advances in the
management of peanut allergy (oral immunotherapy and epicutaneous
immunotherapy). Allergy Asthma Proc. 2020;41(1):5-9.
112. Foong RX, Dantzer JA, Wood RA,
Santos AF. Improving Diagnostic Accuracy in Food Allergy. J
Allergy Clin Immunol Pract. 2021;9(1):71-80.
113. Santos AF, Barbosa-Morais NL,
Hurlburt BK, et al. IgE to epitopes of Ara h 2 enhance the diagnostic
accuracy of Ara h 2-specific IgE. Allergy. 2020.
114. Santos AF, Du Toit G, O’Rourke
C, et al. Biomarkers of severity and threshold of allergic reactions
during oral peanut challenges. J Allergy Clin Immunol.2020;146(2):344-355.
115. Santos AF. Food allergy
severity prediction: quite a way to go yet? Expert Rev Clin
Immunol. 2020;16(6):543-546.
116. Hemmings O, Du Toit G,
Radulovic S, Lack G, Santos AF. Ara h 2 is the dominant peanut allergen
despite similarities with Ara h 6. J Allergy Clin Immunol.2020;146(3):621-630 e625.
117. Sastre J, Rodriguez F, Campo P,
Laffond E, Marin A, Alonso MD. Adverse reactions to immunotherapy are
associated with different patterns of sensitization to grass allergens.Allergy. 2015;70(5):598-600.
118. Calderon MA, Simons FE, Malling
HJ, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy:
mode of action and its relationship with the safety profile.Allergy. 2012;67(3):302-311.
119. Valenta R, Lidholm J,
Niederberger V, Hayek B, Kraft D, Gronlund H. The recombinant
allergen-based concept of component-resolved diagnostics and
immunotherapy (CRD and CRIT). Clin Exp Allergy.1999;29(7):896-904.
120. Matricardi PM, Dramburg S,
Potapova E, Skevaki C, Renz H. Molecular diagnosis for allergen
immunotherapy. J Allergy Clin Immunol. 2019;143(3):831-843.
121. Canonica GW, Bachert C,
Hellings P, et al. Allergen Immunotherapy (AIT): a prototype of
Precision Medicine. World Allergy Organ J. 2015;8(1):31.
122. Matricardi PM, Kleine-Tebbe J.
Molecular Allergology between Precision Medicine and the Choosing Wisely
initiative. Clin Exp Allergy. 2016;46(5):664-667.
123. Di Fraia M, Arasi S, Castelli
S, et al. A new molecular multiplex IgE assay for the diagnosis of
pollen allergy in Mediterranean countries: A validation study.Clin Exp Allergy. 2019;49(3):341-349.
124. Matricardi PM, Potapova E,
Forchert L, Dramburg S, Tripodi S. Digital allergology: Towards a
clinical decision support system for allergen immunotherapy.Pediatr Allergy Immunol. 2020;31 Suppl 24:61-64.
125. Kleine-Tebbe J, Matricardi PM,
Hamilton RG. Allergy Work-Up Including Component-Resolved Diagnosis: How
to Make Allergen-Specific Immunotherapy More Specific. Immunol
Allergy Clin North Am. 2016;36(1):191-203.
126. Sastre J, Landivar ME,
Ruiz-Garcia M, Andregnette-Rosigno MV, Mahillo I. How molecular
diagnosis can change allergen-specific immunotherapy prescription in a
complex pollen area. Allergy. 2012;67(5):709-711.
127. Sastre J, Sastre-Ibanez M.
Molecular diagnosis and immunotherapy. Curr Opin Allergy Clin
Immunol. 2016;16(6):565-570.
128. Agache I, Lau S, Akdis CA, et
al. EAACI Guidelines on Allergen Immunotherapy: House dust mite-driven
allergic asthma. Allergy. 2019;74(5):855-873.
129. Pajno GB, Fernandez-Rivas M,
Arasi S, et al. EAACI Guidelines on allergen immunotherapy: IgE-mediated
food allergy. Allergy. 2018;73(4):799-815.
130. Barber D, Diaz-Perales A,
Villalba M, Chivato T. Challenges for allergy diagnosis in regions with
complex pollen exposures. Curr Allergy Asthma Rep.2015;15(2):496.
131. Shamji MH, Akdis CA, Barber D,
et al. EAACI Research and Outreach Committee: Improving standards and
facilitating global collaboration through a Research Excellence Network.Allergy. 2020;75(8):1899-1901.
132. Gomez-Casado C, Villasenor A,
Rodriguez-Nogales A, Bueno JL, Barber D, Escribese MM. Understanding
Platelets in Infectious and Allergic Lung Diseases. Int J Mol
Sci. 2019;20(7).
133. Blank S, Bilo MB, Ollert M.
Component-resolved diagnostics to direct in venom immunotherapy:
Important steps towards precision medicine. Clin Exp Allergy.2018;48(4):354-364.
Table 1: Characteristics and significance of pollen, vegetables, mites
and epithelia allergens available for CRD and relevant for AIT decisions