Arquivos de Asma, Alergia e Imunologia
https://aaai-asbai.org.br/article/doi/10.5935/2526-5393.20200069
Arquivos de Asma, Alergia e Imunologia
Artigo Original

Characterization of the sensitization profile of bee venom allergic patients – Association with the severity of reaction?

Caracterização do perfil de sensibilização molecular de doentes alérgicos à picada de abelha - Associação com a gravidade da reação?

Catarina Coutinho; Fernando Pineda; Miriam Castillo; Elisa Pedro; Maria Conceição Pereira-Santos

Downloads: 0
Views: 28

Abstract

Introduction: Bee venom (BV) allergy, a common cause of anaphylaxis in adults, is often associated with severe reactions. The use of component-resolved diagnostics (CRD) increases diagnostic accuracy. Objectives: To characterize the sensitization profile of BV allergic patients and a possible correlation with the severity of reaction. Materials and methods: We selected patients with a clinical history of BV allergy, positive skin tests, and specific IgE (sIgE) for BV. The allergenic profile was analyzed by both CRD and Western blot using a well-defined and properly characterized BV extract. Results: Forty-four patients were included, 30 (68.2%) were men. Mean age was 48.9 (SD 17.9) years. Eleven (25%) had large local reactions (LLRs) and 33 (75%) had systemic sting reactions (SSRs). One patient with negative sIgE for BV had positive sIgE for Api m 1, Api m 5, and Api m 10. The sensitization frequency for BV, Api m 1, Api m 2, Api m 3, Api m 5, and Api m 10 was 97.7%, 75%, 47.7%, 20.5%, 40.9%, and 61.4%, respectively. Five patients (11.4%) were sensitized to all BV components. CRD association showed that 5 patients (11.4%) were sensitized only to Api m 1, 8 (18.2%) to Api m 1/Api m 3/Api m 10, and 16 (36.6%) to Api m 1/ Api m 10. Twenty-eight patients (84.8%) with SSRs were sensitized to Api m 1, and concomitant sensitization to Api m 1/Api m 10 was detected in 20 (60.6%). There was a significant difference in Api m 1 between patients with LLRs and SSRs (p = 0.0104). Similar profiles were identified by Western blot analysis, with relevance for the detection of Api m 6 in 28 (64%) and Api m 4 in 16 (36%) patients. Conclusion: The analysis of the sensitization profile using CRD and the association of several of these components can increase diagnostic accuracy in BV allergy. Our data showed that concomitant sensitization to Api m 1 and Api m 10, detected by both CRD and electrophoretic profile, may be associated with SSRs. We emphasize the identification of sensitization to Api m 6 in >50% of patients, which may be considered a major allergen, and to Api m 4, which may be related to reactions during BV immunotherapy

Keywords

Allergy, bee venom, systemic sting reaction, large local reaction, molecular diagnosis, Western blot.

Resumo

Introdução: A alergia ao veneno de abelha (VA) é uma causa frequente de anafilaxia em adultos e está muitas vezes associada a reações graves. O diagnóstico por componentes moleculares (CRD) contribui para uma melhor caracterização desta alergia. Objetivos: Caracterização do perfil de sensibilização molecular de doentes alérgicos ao veneno de abelha e possível correlação com a gravidade da reação. Material e métodos: Selecionaram-se doentes com história de alergia a VA, testes cutâneos e IgE específica (sIgE) positivos para VA. Avaliou-se o perfil alergênico por CRD e por Western Blot, utilizando extrato de VA bem caracterizado. Resultados: 44 doentes, 30 (68,2%) sexo masculino. Média de idades 48,9 ± 17,9 anos, 11 (25%) com reacções locais exuberantes e 33 (75%) com reações sistêmicas à picada (SSR). Um doente tinha sIgE negativa para VA, mas Api m 1, Api m 5 e Api m 10 positivas. A frequência de sensibilização para VA, Api m 1, Api m 2, Api m 3, Api m 5 e Api m 10 foi 97,7%; 75%; 47,7%; 20,5%; 40,9% e 61,4%, respectivamente. Cinco (11,4%) doentes estavam sensibilizados a todos os componentes. Por associação de CRD, detectaram-se 5 (11,4%) doentes sensibilizados apenas a Api m 1, 8 (18,2%) a Api m 1/Api m 3/Api m 10, e 16 (36,6%) a Api m 1/Api m 10. Vinte e oito (84,8%) doentes com SSR tinham Api m 1 positiva e 20 (60,6%) tinham Api m 1/Api m 10 simultaneamente positivas. Observou-se uma diferença estatisticamente significativa para a Api m 1 entre doentes com reações locais exuberantes e sistêmicas (p = 0,0104). Os perfis detectados por Western Blot foram semelhantes, de referir, à detecção de Api m 6 em 28 (64%) e Api m 4 em 16 (36%) dos doentes. Conclusão: A análise do perfil de sensibilização através de CRD e a sua associação aumentam a precisão do diagnóstico de alergia a VA. Sensibilização simultânea a Api m 1 e Api m 10 identificados tanto por CRD como por perfil eletroforético, pode estar associada à ocorrência de SSR. Destaca-se a sensibilização a Api m 6 em > 50% dos doentes, podendo ser considerado um alergênio major, e a Api m 4, possivelmente associado a reações durante a imunoterapia com VA.

Palavras-chave

Alergia, veneno de abelha, reação local exuberante, reação sistêmica à picada, diagnóstico molecular, Western Blot.

Referências

1. Sturm GJ, Varga EM, Roberts G, Mosbech H, Bilò MB, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy. Allergy. 2018;73(4):744-64.

2. Bonifazi F, Bilo BM. Epidemiology of insect-venom anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8:330-7.

3. Worm M, Scherer K, Lang R, Cardona V. First European data from the network of severe allergic reactions (NORA). Eur J Allergy Clin Immunol. 2014;69(4):1397-404.

4. Tavares B. Alergia a veneno de himenópteros: novos métodos de diagnóstico. Acta Med Port. 2005;18(6):445-52.

5. Dhami S, Zaman H, Varga EM, Sturm GJ, Muraro A, Akdis CA, et al. Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis. Allergy. 2017;72(3):342-65.

6. Bilò MB, Pravettoni V, Bignardi D, Bonadonna P, Mauro M, Novembre E, et al. Hymenoptera venom allergy: Management of children and adults in clinical practice. J Investig Allergol Clin Immunol. 2019;29(3):180-205.

7. Sánchez-Machín I, Moreno C, González R, Iglesias-Souto J, Pérez E, Matheu V. Safety of a 2-visit cluster schedule of venom immunotherapy in outpatients at risk of life-threatening anaphylaxis. J Investig Allergol Clin Immunol. 2010;20(1):91-2.

8. Treudler R, Simon JC. Overview of component resolved diagnostics. Curr Allergy Asthma Rep. 2013;13(1):110-7.

9. WHO/IUIS Allergen Nomenclature Subcommittee. Allergen nomenclature.

10. Köhler J, Blank S, Müller S, Bantleon F, Frick M, Huss-Marp J, et al. Component resolution reveals additional major allergens in patients with honeybee venom allergy. J Allergy Clin Immunol. 2014;133(5):1383-9.

11. Alfaya Arias T, Soriano Gómis V, Soto Mera T, Vega-Castro A, Vega Gutiérrez JM, Alonso Llamazares A, et al. Key issues in hymenoptera venom allergy: An update. J Investig Allergol Clin Immunol. 2017;27(1):19-31.

12. Antolín-Amérigo D, Ruiz-León B, Boni E, Alfaya Arias T, ÁlvarezMon M, Barbarroja-Escudero J, et al. Component-resolved diagnosis in hymenoptera allergy. Allergol Immunopathol (Madr). 2018;46(3):253‑62.

13. Blank S, Seismann H, Michel Y, McIntyre M, Cifuentes L, Braren I, et al. Api m 10, a genuine A. mellifera venom allergen, is clinically relevant but underrepresented in therapeutic extracts. Allergy. 2011;66(10):1322-9.

14. Mueller H. Diagnosis and treatment of insect sensitivity. J Asthma Res. 1966;3(4):331-3.

15. Vega-Castro A, Rodriguez-Gil D, Martínez-Gomariz M, Gallego R, Peña M, Palacios R. Api m 6 and Api m 10 as Major Allergens in Patients with Honeybee Venom Allergy. J Investig Allergol Clin Immunol. 2020;32(2).

16. Jakob T, Rafei-Shamsabadi D, Spillner E, Müller S. Diagnostics in Hymenoptera venomallergy: current concepts and developments with special focus onmolecular allergy diagnostics. Allergo J Int. 2017;26:93-105.

17. Hofmann S, 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. J Allergy Clin Immunol. 2011;127:265-7.

18. Müller U, Schmid-Grendelmeier, P Hausmann O, Helbling A. IgE to recombinant allergens Api m 1, Ves v 1, and Ves v 5 distinguish double sensitization from crossreaction in venom allergy. Allergy. 2012;67:1069-73.

19. Korošec P, Valenta R, Mittermann I, Celesnik N, Erzen R, Zidarn M, et al. Low sensitivity of commercially available rApim1 for diagnosis of honeybee venomallergy. J Allergy Clin Immunol. 2011;128:671-3.

20. Sturm GJ, Hemmer W, Hawranek T, Lang R, Ollert M, Spillner E, et al. Detection of IgE to recombinant Api m1 and rVes v5 is valuable but not sufficient to distinguish bee from wasp venom allergy. J Allergy Clin Immunol. 2011;128:247-8.

21. Grunwald T, Bockisch B, Spillner E, Ring J, Bredehorst R, Ollert M. Molecular cloning and expression in insect cells of honeybee venom allergen acid phosphatase (Api m 3). J Allergy Clin Immunol. 2006;117:848-54.

22. Blank S, Seismann H, Bockisch B, Braren I, Cifuentes L, McIntyre M, et al. Identification, recombinant expression, and characterization of the 100kDa high molecular weight Hymenoptera venom allergens Api m 5 and Ves v 3. J Immunol. 2010;184:5403-13.

23. Ruiz B, Serrano P, Moreno C. IgE-Api m 4 is useful for identifying a particular phenotype of bee venom allergy. J Investig Allergol Clin Immunol. 2016;26(6):355-61.

24. Ruiz B, Serrano P, Verdú 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):350-2.

25. Frick M, Fischer J, Helbling A, Rueff F, Wieczoreck D, Ollert M, et al. Predominant Api m 10 sensitization as risk factor for treatment failure in honey bee venom immunotherapy. J Allergy Clin Immunol. 2016;138(6):1663-71.e9.

26. Ollert M, Blank S. Anaphylaxis to insect venom allergens: Role of molecular diagnostics. Curr Allergy Asthma Rep. 2015;15(5):26.

27. Pereira Santos MC, Lourenço T, Pedro E, Pereira Barbosa M, Branco Ferreira M. Evolution of Api m 10 specific IgE and IgG4 after one year of bee venom immunotherapy. Eur Ann Allergy Clin Immunol. 2020;52(4):175-81.

28. 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.


Submetido em:
27/11/2020

Aceito em:
05/12/2020

6a184c86a95395492b0758af aaai Articles
Links & Downloads

Arq Asma Alerg Imunol

Share this page
Page Sections