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Jonas Lidholm - One of the best experts on this subject based on the ideXlab platform.
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ige recognition patterns in peanut allergy are age dependent perspectives of the europrevall study
Allergy, 2015Co-Authors: B K Ballmerweber, Jonas Lidholm, Montserrat Fernandezrivas, Suranjith L Seneviratne, K M Hanschmann, Lothar Vogel, P Bures, Philipp Fritsche, Colin Summers, Andre C KnulstAbstract:BACKGROUND: We tested the hypothesis that specific molecular Sensitization patterns correlate with the clinical data/manifestation in a European peanut allergic population characterized under a common protocol. METHODS: 68 peanut allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting-dose were established by double-blind placebo-controlled food-challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD were determined using ImmunoCAP. RESULTS: 78% of peanut allergics were sensitised to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut allergic population. Geographic differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitisation to rAra h 1 and 2 were exclusively observed in early onset peanut allergy. Peanut tolerant subjects were frequently sensitised to rAra h 8 or 9 but not to storage proteins. Sensitisation to Ara h 2 ≥1.0 kUA /L conferred a 97% probability for a systemic reaction (p=0.0002). Logistic regression revealed a significant influence of peanut extract Sensitization and region on the occurrence of systemic reactions (p=0.0185 and p=0.0436 respectively). CONCLUSION: Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥1.0 kUA /L is significantly associated with the development of systemic reactions to peanut. This article is protected by copyright. All rights reserved.
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component resolution reveals additional major allergens in patients with honeybee venom allergy
The Journal of Allergy and Clinical Immunology, 2014Co-Authors: Julian Kohler, Edzard Spillner, Simon Blank, J Hussmarp, Jonas Lidholm, Sabine Muller, Frank I Bantleon, Marcel Frick, Thilo JakobAbstract:Background Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of Sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. Objective We performed an analysis of Sensitization profiles of patients with HBV allergy to a panel of HBV allergens. Methods Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. Results IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen–specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3– and Api m 10–specific IgG 4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. Conclusion Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed Sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations.
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prevalence and distribution of Sensitization to foods in the european community respiratory health survey a europrevall analysis
Allergy, 2010Co-Authors: Peter Burney, S Chinn, C Summers, Richard Hooper, R Van Ree, Jonas LidholmAbstract:To cite this article: Burney P, Summers C, Chinn S, Hooper R, van Ree R, Lidholm J. Prevalence and distribution of Sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis. Allergy 2010; 65: 1182–1188. Abstract Background: Reports of adverse reactions to foods are increasing, but there is limited information on the comparative prevalence of Sensitization to food allergens using standardized methods. Methods: Sera from the ‘random sample’ of young adults seen during the second phase of the European Community Respiratory Health Survey were analysed for IgE against 24 foods using ImmunoCAP. Sera were tested on five food mixes, and subsequently on individual foods in each positive mix. Results: Sera from 4522 individuals living in 13 countries were tested for at least one food allergen mix. Prevalence of Sensitization to any of the 24 food allergens ranged from 24.6% in Portland (USA) to 7.7% in Reykjavik (Iceland). With few exceptions, the relative prevalence of Sensitization to different foods was similar in all countries. Sensitization rates to egg, fish and milk were each less than 1%, and the most common Sensitizations are not represented in current commercial mixes. The prevalence of Sensitization to foods was not related to that of Sensitization to aeroallergens but was related to the geometric mean total IgE for the country. Conclusions: Sensitization to foods is common but highly variable. The relative prevalence of Sensitization to different foods is more consistent than would be expected by chance, suggesting that quantity of consumption of specific foods does not determine prevalence. The aetiology of food Sensitization is only partly similar to that for aeroallergens but is related to local levels of total IgE. This may provide an important clue to the origins of food Sensitization.
G Salcedo - One of the best experts on this subject based on the ideXlab platform.
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lipid transfer protein syndrome clinical pattern cofactor effect and profile of molecular Sensitization to plant foods and pollens
Clinical & Experimental Allergy, 2012Co-Authors: Mariona Pascal, Arantxa Palacín, R Munozcano, Z Reina, Ramon Vilella, Cesar Picado, Manel Juan, J Sanchezlopez, Maria Rueda, G SalcedoAbstract:SummaryBackground Multiple plant-food Sensitizations with a complex pattern of clinical manifestations are a common feature of lipid transfer protein (LTP)-allergic patients. Component-resolved diagnosis permits the diagnosis of the allergen Sensitization profile. Objective We sought to clinically characterize and describe the plant-food and pollen molecular Sensitization profile in patients with LTP syndrome. Methods Forty-five subjects were recruited, after being diagnosed with multiple plant-food allergies sensitized to LTP, but not to any other plant-food allergen, according to the molecular allergen panel tested (Pru p 3 (LTP), Pru p 1 (Bet v 1-like), Pru p 4 (profilin) and those included in a commercial microarray of 103 allergenic components). IgE-mediated food-allergy symptoms and pollinosis were collected. Patients were skin prick tested with a plant-food and pollens panel, and specific IgE to Tri a 14 was evaluated. Results A heterogeneous group of plant-foods was involved in local and systemic symptoms: oral allergy syndrome (75.6%), urticaria (66.7%), gastrointestinal disorders (55.6%) and anaphylaxis (75.6%), 32.4% of which were cofactor dependent (Non-Steroidal Anti-inflammatory Drugs, exercise). All tested subjects were positive to peach and Pru p 3, Tri a 14 and to some of the LTPs included in the microarray. Pollinosis was diagnosed in 75.6% of subjects, with a broad spectrum of pollen and pollen-allergen Sensitization. Plane tree and mugwort were the statistically significant pollens associated with Pru p 3. Conclusions and Clinical Relevance Several plant-foods, taxonomically unrelated, independent of peach involvement, are implicated in LTP syndrome. Local symptoms should be evaluated as a risk marker for anaphylaxis because they are frequently associated with cofactor-dependent anaphylaxis. The association of these symptoms with pollinosis, especially plane tree pollinosis, could be part of this syndrome in our area.
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component resolved diagnosis of pollen allergy based on skin testing with profilin polcalcin and lipid transfer protein pan allergens
Clinical & Experimental Allergy, 2009Co-Authors: D Barber, Manuel Lombardero, F De La Torre, Mayte Villalba, A I Tabar, I Antepara, C Colas, I Davila, C Vidal, G SalcedoAbstract:BACKGROUND Allergy diagnosis needs to be improved in patients suffering from pollen polySensitization due to the existence of possible confounding factors in this type of patients. OBJECTIVE To evaluate new diagnostic strategies by comparing skin responses to pan-allergens and conventional allergenic extracts with specific IgE (sIgE) to purified allergen molecules. METHODS One thousand three hundred and twenty-nine pollen-allergic patients were diagnosed by a combination of an in vitro method with a panel of 13 purified allergens, including major allergens and pan-allergens, using a high-capacity screening technology (ADVIA-Centaur®) and skin prick test (SPT) to pan-allergens and conventional extracts. RESULTS There was a high concordance (κ index) between in vitro (sIgE to major allergens) and in vivo (SPT to conventional extracts) methods in patients who were not sensitized to pan-allergens, but SPT with conventional extracts failed to diagnose patients with Sensitization to pan-allergens. In patients who were simultaneously sensitized to polcalcins and profilins, there was a duplication both in the number of Sensitizations to major allergens and in the years of disease evolution. There was a statistical association between Sensitization to profilins and/or lipid transfer proteins and food allergy (P<0.0001). CONCLUSION The novel diagnostic strategy has proven to be a valuable tool in daily clinical practice. Introduction of routine SPT to pan-allergens is a simple and feasible way of improving diagnostic efficacy. Patients sensitized to pan-allergens should be tested by an adequate panel of allergenic molecules in order to identify the allergens that are responsible for the allergic disease.
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understanding patient Sensitization profiles in complex pollen areas a molecular epidemiological study
Allergy, 2008Co-Authors: D Barber, Manuel Lombardero, F De La Torre, F Florido, P Guardia, C Moreno, J Quiralte, Mayte Villalba, G Salcedo, Rosalia RodriguezAbstract:Background: Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy. Objective: We studied the Sensitization profile of individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen Sensitizations. Methods: A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur®) in 891 patients. Results: Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin Sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of Sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable. Conclusion: Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient Sensitization. High exposure leads to differential Sensitization profiles some of which are associated with more severe allergic conditions. Profilin Sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen Sensitization.
M. Pignatti - One of the best experts on this subject based on the ideXlab platform.
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Cross-Sensitizations between azo dyes and para-amino compound. A study of 236 azo-dye-sensitive subjects.
Contact Dermatitis, 1997Co-Authors: Stefania Seidenari, L. Mantovani, B. M. Manzini, M. PignattiAbstract:Combined Sensitizations to different azo dyes, probably based both on true cross-Sensitization and on simultaneous positive reactions, have frequently been described. However, since azo dyes are included in the standard series in a minority of countries, the case studies considered comprise, with few exceptions, a small number of subjects. The aim of our study was to investigate cross-reactions between different azo dyes and para-amino compounds in azo-dye-sensitive subjects, to study the clinical aspects of azo dye dermatitis, to assess the relevance of Sensitization to azo dyes, and to relate the pattern of cross-Sensitizations to the chemical structure of the different dyes. Out of 6203 consecutively tested patients, 236 were sensitized to at least 1 of 6 azo compounds employed as textile dyes, included in our standard series. 107 subjects reacted to Disperse Orange 3 (DO3), 104 to Disperse Blue 124 (DB124), 76 to p-aminoazobenzene (PAB), 67 to Disperse Red 1 (DR1), 42 to Disperse Yellow 3 (DY3), and 31 to p-dimethylaminoazobenzene (PDAAB). Co-Sensitizations to para-phenylenediamine were present in most subjects sensitized to DO3 (66%) and PAAB (75%), in 27% and 36% of DR1 and DY3-sensitive subjects, and only in 16% of subjects sensitized to DB124. Apart from the hands and the face, the neck and the axillae were the most frequently involved skin sites. Whereas the involvement of flexural areas was mainly connected with Sensitization to DB124, in patients with hand dermatitis and in those working as hairdressers, Sensitization to DO3 and PAAB was more frequent. Moreover, in the former patient group, a history of textile dye allergy was most frequently obtained. Out of 33 patients tested with an additional textile dye series, only 5 subjects reacted to anthraquinone dyes. Cross-Sensitizations between azo dyes and para-amino compounds can partially be explained on the basis of structural affinities.
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Cross-Sensitizations between azo dyes and para-amino compound - A study of 236 azo-dye-sensitive subjects
1997Co-Authors: Seidenari Stefania, L. Mantovani, M. B. Manzini, M. PignattiAbstract:Combined Sensitizations to different azo dyes, probably based both on true cross-Sensitization and on simultaneous positive reactions, have frequently been described. However, since azo dyes are included in the standard series in a minority of countries, the case studies considered comprise, with few exceptions, a small number of subjects. The aim of our study was to investigate cross-reactions between different azo dyes and para-amino compounds in ate-dye-sensitive subjects, to study the clinical aspects of azo dye dermatitis, to assess the relevance of Sensitization to azo dyes, and to relate the pattern of cross-Sensitizations to the chemical structure of the different dyes. Out of 6203 consecutively tested patients, 236 were sensitized to at least 1 of 6 azo compounds employed as textile dyes, included in our standard series. 107 subjects reacted to Disperse Orange 3 (DO3), 104 to Disperse Blue 124 (DB124): 76 to p-aminoazobenzene (PAB), 67 to Disperse Red 1 (DR1), 42 to Disperse Yellow 3 (DY3), and 31 to p-dimethylaminoazobenzene (PDAAB). Go-Sensitizations to para-phenylenediamine were present in most subjects sensitized to DO3 (66%) and PAAB (75%), in 27% and 36% of DR1 and DY3-sensitive subjects, and only in 16% of subjects sensititzed to DB124. Apart from the hands and the face, the neck and the axillae were the most frequently involved skin sites. Whereas the involvement of flexural areas was mainly connected with Sensitization to DB124, in patients with hand dermatitis and in those working as hairdressers, Sensitization to DO3 and PAAB was more frequent. Moreover, in the former patient group, a history of textile dye allergy was most frequently obtained. Out of 33 patients tested with an additional textile dye series, only 5 subjects reacted to anthraquinone dyes. Cross-Sensitizations between azo dyes and para-amino compounds can partially be explained on the basis of structural affinities
J Pungier - One of the best experts on this subject based on the ideXlab platform.
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quantitative risk assessment for skin sensitisation consideration of a simplified approach for hair dye ingredients
Regulatory Toxicology and Pharmacology, 2012Co-Authors: Carsten Goebel, Harald Schlatter, J F Nicolas, Pieter Jan Coenraads, Brunhilde Blömeke, Thomas L. Diepgen, Axel Schnuch, Maya Krasteva, James S Taylor, J PungierAbstract:With the availability of the local lymph node assay, and the ability to evaluate effectively the relative skin sensitizing potency of contact allergens, a model for quantitative-risk-assessment (QRA) has been developed. This QRA process comprises: (a) determination of a no-expected-sensitisation-induction-level (NESIL), (b) incorporation of Sensitization-assessment-factors (SAFs) reflecting variations between subjects, product use patterns and matrices, and (c) estimation of consumer-exposure-level (CEL). Based on these elements an acceptable-exposure-level (AEL) can be calculated by dividing the NESIL of the product by individual SAFs. Finally, the AEL is compared with the CEL to judge about risks to human health. We propose a simplified approach to risk assessment of hair dye ingredients by making use of precise experimental product exposure data. This data set provides firmly established dose/unit area concentrations under relevant consumer use conditions referred to as the measured-exposure-level (MEL). For that reason a direct comparison is possible between the NESIL with the MEL as a proof-of-concept quantification of the risk of skin Sensitization. This is illustrated here by reference to two specific hair dye ingredients p-phenylenediamine and resorcinol. Comparison of these robust and toxicologically relevant values is therefore considered an improvement versus a hazard-based classification of hair dye ingredients.
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quantitative risk assessment for skin sensitisation consideration of a simplified approach for hair dye ingredients
Regulatory Toxicology and Pharmacology, 2012Co-Authors: Carsten Goebel, Harald Schlatter, J F Nicolas, Pieter Jan Coenraads, Brunhilde Blömeke, Thomas L. Diepgen, Axel Schnuch, Maya Krasteva, James S Taylor, J PungierAbstract:With the availability of the local lymph node assay, and the ability to evaluate effectively the relative skin sensitizing potency of contact allergens, a model for quantitative-risk-assessment (QRA) has been developed. This QRA process comprises: (a) determination of a no-expected-sensitisation-induction-level (NESIL), (b) incorporation of Sensitization-assessment-factors (SAFs) reflecting variations between subjects, product use patterns and matrices, and (c) estimation of consumer-exposure-level (CEL). Based on these elements an acceptable-exposure-level (AEL) can be calculated by dividing the NESIL of the product by individual SAFs. Finally, the AEL is compared with the CEL to judge about risks to human health. We propose a simplified approach to risk assessment of hair dye ingredients by making use of precise experimental product exposure data. This data set provides firmly established dose/unit area concentrations under relevant consumer use conditions referred to as the measured-exposure-level (MEL). For that reason a direct comparison is possible between the NESIL with the MEL as a proof-of-concept quantification of the risk of skin Sensitization. This is illustrated here by reference to two specific hair dye ingredients p-phenylenediamine and resorcinol. Comparison of these robust and toxicologically relevant values is therefore considered an improvement versus a hazard-based classification of hair dye ingredients.
Thilo Jakob - One of the best experts on this subject based on the ideXlab platform.
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current challenges in molecular diagnostics of insect venom allergy
Allergo journal international, 2020Co-Authors: Amilcar Perezriverol, Mario Sergio Palma, Thilo JakobAbstract:Advanced component-resolved diagnostics (CRD) in Hymenoptera venom allergy (HVA) has improved the precise description of individual Sensitization profiles. However, diagnostic gaps, peptide-based cross-reactivity, early identification of severe reactors and diagnosis of patients with a clear history of sting reactions but negative specific IgE and skin tests, remain challenging. Systematic literature search in PubMed and critical analysis of recently published studies on insect venom allergy diagnostics. CRD has increased the sensitivity of IgE testing and improved the discrimination of primary Sensitization from irrelevant cross-reactivity, ultimately providing a better rationale for therapeutic decisions. Despite these major advances, there is still room for improvement in routine HVA diagnostics. Peptide based cross-reactivity among homologous allergens from Vespinae and Polistinae venoms as well as still existing diagnostic gaps are particularly challenging. No marker allergens are currently available to differentiate Vespula and Polistes Sensitizations. Several strategies including clinical setting of basophil activation test (BAT) for routine diagnostics, venomic analysis for the identification of novel allergens and characterization of the molecular basis of cross-reactivity could be used to address major limitations and unresolved issues in molecular diagnostics of HVA.
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component resolved diagnostics for hymenoptera venom allergy
Current Opinion in Allergy and Clinical Immunology, 2017Co-Authors: Thilo Jakob, U Muller, A Helbling, Edzard SpillnerAbstract:PURPOSE OF REVIEW Component-resolved diagnostics makes use of defined allergen molecules to analyse IgE-mediated Sensitizations at a molecular level. Here, we review recent studies on the use of component-resolved diagnostics in the field of Hymenoptera venom allergy (HVA) and discuss its benefits and limitations. RECENT FINDINGS Component resolution in HVA has moved from single molecules to panels of allergens. Detection of specific immunoglobulin E (sIgE) to marker and cross-reactive venom allergens has been reported to facilitate the discrimination between primary Sensitization and cross-reactivity and thus, to provide a better rationale for prescribing venom immunotherapy (VIT), particularly in patients sensitized to both honeybee and vespid venom. Characterization of IgE reactivity to a broad panel of venom allergens has allowed the identification of different Sensitization profiles that in honeybee venom allergy were associated with increased risks for side effects or treatment failure of VIT. In contrast, component resolution so far has failed to provide reliable markers for the discrimination of Sensitizations to venoms of different members of Vespidae. SUMMARY Component-resolved diagnostics allows a better understanding of the complexity of Sensitization and cross-reactivities in HVA. In addition, the enhanced resolution and precision may allow identification of biomarkers, which can be used for risk stratification in VIT. Knowledge about the molecular composition of different therapeutic preparations may enable the selection of appropriate preparations for VIT according to individual Sensitization profiles, an approach consistent with the goals of personalized medicine.
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heterogeneity of molecular Sensitization profiles in grass pollen allergy implications for immunotherapy
Clinical & Experimental Allergy, 2014Co-Authors: Ulf Darsow, Magnus P Borres, Florian Pfab, Knut Brockow, Thilo Jakob, Heidrun Behrendt, J. Ring, Carl Johan Petersson, J HussmarpAbstract:BackgroundData on molecular allergy diagnostics in adults with grass pollen allergy with regard to conjunctival and nasal provocation test outcome and specific immunotherapy are lacking to date. ObjectiveTo assess whether molecular allergy diagnostics for grass pollen allergens could help with predicting provocation test outcomes and serve as a basis for future component-resolved specific immunotherapy. MethodsSera of 101 adults with grass pollen allergy was analysed for IgE against timothy grass pollen (Phleum pratense), rPhl p 1, rPhl p 2, nPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11 and rPhl p12 and correlated with the individuals' outcome in the nasal and conjunctival provocation tests and investigated in regard to a potential component-resolved specific immunotherapy. ResultsAn increasing number of Sensitizations to timothy grass allergens was correlated to a positive reaction in the conjunctival (4.9 vs. 3.6, P=0.003) and nasal provocation tests (4.5 vs. 2.2, P=0.0175). In molecular Sensitization profiles, a substantial heterogeneity was detected, with none of the patients exactly matching the allergen composition of a previously published component-resolved specific immunotherapy containing Phl p 1, Phl p 2, Phl p 5a/b and Phl p 6. The results indicate that in 95% of the patients, a proportion of 50% of timothy-IgE would be targeted with such a specific immunotherapy, while in 50% and 10% of patients, 80% and 90% of timothy-IgE would be targeted, respectively. Conclusion and Clinical RelevanceMolecular allergy diagnostics is a prerequisite for future component-resolved specific immunotherapy due to the high heterogeneity of Sensitization profiles. However, of current clinical relevance is the observed correlation between the number of Sensitizations and provocation test outcome.
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component resolution reveals additional major allergens in patients with honeybee venom allergy
The Journal of Allergy and Clinical Immunology, 2014Co-Authors: Julian Kohler, Edzard Spillner, Simon Blank, J Hussmarp, Jonas Lidholm, Sabine Muller, Frank I Bantleon, Marcel Frick, Thilo JakobAbstract:Background Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of Sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. Objective We performed an analysis of Sensitization profiles of patients with HBV allergy to a panel of HBV allergens. Methods Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. Results IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen–specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3– and Api m 10–specific IgG 4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. Conclusion Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed Sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations.