Using the A-RISC index to predict IgE cross-reactivity in legume allergens: An in silico approach
Main Article Content
Keywords
Legume Allergens, Cross-reactivity, A-RISC Index, In Silico, Component-resolved Diagnosis, Food Allergy
Abstract
Introduction: Legumes are a common source of allergic sensitization in many regions worldwide. Structural similarity among homologous proteins can lead to IgE-mediated cross--reactivity. In this context, in silico analysis offers a valuable approach to predict potential molecular interactions among related allergens and to support the interpretation of risk in patients with multiple sensitizations.
Methods: An in silico analysis was conducted to evaluate sequence homology, structural conservation, and surface exposure of IgE epitopes across five major protein families: 11S globulins, 7S globulins, 2S albumins, nsLTPs, and PR-10. Tools included multiple sequence alignment, A-RISC index calculation, and 3D visualization with ChimeraX.
Results: PR-10 proteins exhibited high homology (A-RISC >0.75), suggesting a high risk of cross-reactivity. Vicilins and glycinins showed intermediate similarity (A-RISC 0.45–0.57), while nsLTPs and 2S albumins displayed low A-RISC values (<0.50), although conserved structural motifs were identified in immunologically relevant regions.
Conclusion: This in silico approach enables early identification of cross-reactivity potential, reinforces the value of component-resolved molecular diagnostics, and contributes to improved food labeling, clinical decision-making, and nutritional safety in patients with -multiple sensitizations.
References
2. Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014;133(2):291–307. 10.1016/j.jaci.2013.11.020
3. Sánchez A, Sánchez J, Cardona R. Results and limitations of epidemiological studies on food allergy. Focus on tropical countries. Rev Alerg Mex. 2019;66(1):9–17. 10.29262/ram.v66i1.340
4. Besler M, Steinhart H, Paschke A. Stability of food allergens and allergenicity of processed foods [Internet]. J Chromatography B. 2001. Available from: www.elsevier.com/locate/chromb
5. Breiteneder H, Mills ENC. Molecular properties of food allergens. J Allergy Clin Immunol. 2005;115(1):14–23. 10.1016/j.jaci.2004.10.022
6. Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes. EFSA J. 2014;12(11):3894. 10.2903/j.efsa.2014.3894
7. Hoffmann-Sommergruber K, Hilger C, Santos A, De Las Vecillas L, Dramburg S. Molecular Allergology User’s Guide 2.0. 2023;34 Suppl 28:e13854. 10.1111/pai.13854
8. Pomés A, Davies JM, Gadermaier G, Hilger C, Holzhauser T, Lidholm J, et al. WHO/IUIS Allergen Nomenclature: Providing a common language. Mol Immunol. 2018;100:3–13. 10.1016/j.molimm.2018.03.003
9. Chruszcz M, Kapingidza AB, Dolamore C, Kowal K. A robust method for the estimation and visualization of IgE cross--reactivity likelihood between allergens belonging to the same protein family. PLoS One. 2018;13(11):e0208276. 10.1371/journal.pone.0208276
10. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7:539. 10.1038/msb.2011.75
11. Ffitima Ferreira B, Hirtenlehner K, Jilek A, Godnik-Cvarfl Heimo Breiteneder J, Grimm R, Karin Hoffmann-Sommergruber I, et al. Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: Potential use of hypoallergenic isoforms for immunotherapy. 1996:183(2):599–609. 10.1084/jem.183.2.599
12. Mittag D, Vieths S, Vogel L, Wagner-Loew D, Starke A, Hunziker P, et al. Birch pollen-related food allergy to legumes: Identification and characterization of the Bet v 1 homologue in mungbean (Vigna radiata), Vig r 1. Clin Exp Allergy. 2005;35(8):1049–55. 10.1111/j.1365-2222.2005.02309.x
13. Palladino C, Breiteneder H. Peanut allergens. Mol Immunol. 2018;100:58–70. 10.1016/j.molimm.2018.04.005
14. Salcedo G, Sánchez-Monge R, Barber D, Díaz-Perales A. Plant non-specific lipid transfer proteins: An interface between plant defence and human allergy. Biochim Biophys Acta. 2007;1771(6):781–91. 10.1016/j.bbalip.2007.01.001
15. Borges JP, Barre A, Culerrier R, Granier C, Didier A, Rougé P. Lipid transfer proteins from Rosaceae fruits share consensus epitopes responsible for their IgE-binding cross-reactivity. Biochem Biophys Res Commun. 2008;365(4):685–90. 10.1016/j.bbrc.2007.11.046
16. López-Torrejón G, Salcedo G, Martín-Esteban M, Díaz-Perales A, Pascual CY, Sánchez-Monge R. Len c 1, a major allergen and vicilin from lentil seeds: Protein isolation and cDNA cloning. J Allergy Clin Immunol. 2003;112(6):1208–15. 10.1016/j.jaci.2003.08.035
17. L’Hocine L, Boye JI. Allergenicity of soybean: New developments in identification of allergenic proteins, cross-reactivities and hypoallergenization technologies. Crit Rev Food Sci Nutr. 2007;47(2):127–43. 10.1080/10408390600626487
18. Chruszcz M, Maleki SJ, Majorek KA, Demas M, Bublin M, Solberg R, et al. Structural and immunologic characterization of Ara h 1, a major peanut allergen. J Biol Chem. 2011;286(45):39318–27. 10.1074/jbc.M111.270132
19. Moreno FJ, Clemente A. 2S Albumin storage proteins: What makes them food allergens? Open Biochem J. 2008;2:16–28. 10.2174/1874091X00802010016
20. Bueno-Díaz C, Martín-Pedraza L, Parrón J, Cuesta-Herranz J, Cabanillas B, Pastor Vargas C, Batanero E, Villalba M. Characterization of relevant biomarkers for the diagnosis of food allergies: An overview of the 2S albumin family. Foods. 2021;10(6):1235. 10.3390/foods10061235
21. Dreskin SC, Koppelman SJ, Andorf S, Nadeau KC, Kalra A, Braun W, et al. The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts, and sesame seeds. J Allergy Clin Immunol. 2021;147(4):1154–63. 10.1016/j.jaci.2020.11.004
22. Sirvent S, Palomares O, Cuesta-Herranz J, Villalba M, Rodríguez R. Analysis of the structural and immunological stability of 2S albumin, nonspecific lipid transfer protein, and profilin allergens from mustard seeds. J Agric Food Chem. 2012;60(23):6011–8. 10.1021/jf300555h