Api m 10
Summary
Api m 10, a low abundance glycoprotein from Apis mellifera (honeybee) venom (HBV), of unknown biological function, is a major allergen of HBV and a marker allergen for genuine sensitization to this venom. Api m 10 is underrepresented in HBV extracts, negatively affecting the outcome of venom immunotherapy (VIT) in HBV allergic patients with dominant Api m 10 sensitization.
Epidemiology
Worldwide distribution
Api m 10 sensitization has a prevalence of 26% to 75% among HBV-allergic populations ([1-3]) and is usually considered a major allergen in HBV-allergic patients. Api m 10 monosensitization is usually not observed in HBV allergic patients [2-4], and concerns a low percentage of patients when it is identified, less than 5% [4, 5].
Clinical Relevance
Specific molecules
Api m 10 is a marker allergen for HBV genuine sensitization, as it does not cross-react with allergens from other Hymenoptera venoms [1].
Disease severity
Neither the prevalence, nor the level of Api m 10-specific IgE can distinguish between patients experiencing severe versus non severe systemic reactions to HBV stings, nor between HBV allergic and asymptomatic HBV sensitized subjects [1, 3]. However, Api m 10 prevalence and specific IgE levels were reportedly lower in HBV allergic patients experiencing severe adverse effects (SAEs) during VIT compared with those without SAEs (20% and 33%, p 0.04, and median + interquartile range <0.35 + 0.29 kUA/L versus 0.35+0 kUA/L, p 0.03) [3].
Cross-reactive molecules
No cross-reactive allergen has been described so far for Api m 10 [1, 7].
Disease severity
Various patterns of sensitization to HBV allergens have been described, but no clinical correlate of severity has been identified so far [1].
Diagnostics
Diagnosis of genuine sensitization to Apis mellifera venom
Api m 10 is a marker allergen for HBV sensitization. Therefore, the demonstration of specific IgE to Api m 10 confirms genuine sensitization to HBV [1, 10].
With a prevalence of up to 75% in HBV-allergic patients, IgE to Api m 10 is a relevant clinical tool [1]. However, using a panel of HBV marker allergens in addition to Api m 1 and Api m 10 increases the chance of demonstrating genuine sensitization to HBV [1, 2, 5, 11].
Disease severity
In Hymenoptera venom IgE testing, the quantitative result of specific IgE to a molecular allergen or whole venom extract is neither predictive of, nor correlated to the severity of the reaction [1].
Sensitivity of in vitro assays
The prevalence of sensitization to individual HBV allergens, including Api m 10, in HBV-allergic patients varies depending on multiple factors such as geography, patient inclusion criteria, single or double positivity to HBV and Vespid venoms, use of a recombinant allergen from bacterial or insect cell expression versus a natural purified allergen, and assay format [1-3, 5, 7]. Thus, the diagnostic sensitivity of specific IgE to rApi m 10 ranges from 26 to 75% in HBV-allergic patients [1, 2, 5, 7, 11].
Api m 10 sensitization can be detected with commercially available singleplex methods.
Diagnostic specificity
No IgE binding to rApi m 10 was reported in subjects without detectable IgE to HBV whole allergen extract, nor in Vespid-allergic patients without HBV sensitization, and the diagnostic specificity of IgE to rApi m 10 in HBV allergic patients was calculated at 97.6% in a performance study [2, 5, 6, 11].
AIT Prescription
Demonstrated sensitization to Api m 10 confirms genuine sensitization to HBV, thus supporting the accurate diagnosis in patients with double sensitivity to HBV and Vespid venom extracts, as well as in patients with inconsistent clinical history and skin prick tests, and guiding the choice of HBV AIT in eligible patients [1].
Api m 10 sensitization has been associated with poorer responses to, or even therapeutic failure of, HBV VIT, especially in patients with dominant Api m 10 sensitization, i.e. with levels of specific IgE to Api m 10 higher than 50% of the level of specific IgE to HBV extract [1, 6, 7]. This is of particular concern in areas with a high prevalence of Api m 10 sensitization, where dominant Api m 10 sensitization was reported in 10 to 12% of HBV allergic patients [7]. Conversely, a study on 332 HBV allergic patients receiving VIT reported significantly lower figures of prevalence and levels of Api m 10 specific IgE in patients experiencing SAEs as compared to those who did not experience SAEs during VIT [3].
Taken together, these data suggest that in HBV allergic patients with Api m 10 dominant sensitization, VIT should be undertaken with therapeutic HBV extracts with detectable Api m 10 amounts [7].
Prevention And Therapy
Experimental trials
Linear IgE epitope mapping of Api m 10 has identified a peptide with broad recognition that opens the perspective of therapeutic development for immunotherapy [7].
References
- Dramburg S, Hilger C, Santos AF, de Las Vecillas L, Aalberse RC, Acevedo N, et al. EAACI Molecular Allergology User's Guide 2.0. Pediatr Allergy Immunol. 2023;34 Suppl 28:e13854.
- Vega-Castro A, Rodriguez-Gil D, Martinez-Gomariz M, Gallego R, Pena MI, Palacios R. Api m 6 and Api m 10 as Major Allergens in Patients With Honeybee Venom Allergy. J Investig Allergol Clin Immunol. 2022;32(2):116-23.
- Kopac P, Custovic A, Zidarn M, Silar M, Selb J, Bajrovic N, et al. Biomarkers of the Severity of Honeybee Sting Reactions and the Severity and Threshold of Systemic Adverse Events During Immunotherapy. J Allergy Clin Immunol Pract. 2021;9(8):3157-63 e5.
- Jovanovic D, Peric-Popadic A, Djuric V, Stojanovic M, Lekic B, Milicevic O, et al. Molecular diagnostics and inhibition of cross-reactive carbohydrate determinants in Hymenoptera venom allergy. Clin Transl Allergy. 2023;13(3):e12230.
- Kohler J, Blank S, Muller 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, 9 e1-6.
- 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.
- Jakob T, Rauber MM, Perez-Riverol A, Spillner E, Blank S. The Honeybee Venom Major Allergen Api m 10 (Icarapin) and Its Role in Diagnostics and Treatment of Hymenoptera Venom Allergy. Curr Allergy Asthma Rep. 2020;20(9):48.
- UniProt. UniProt Q5BLY4 for Api m 10 2023 [Available from: https://www.uniprot.org/uniprotkb/Q5BLY4/entry.
- IUIS/WHO. IUIS/WHO Apis mellifera 2023 [Available from: http://allergen.org/search.php?allergenname=&allergensource=apis+mellifera&TaxSource=&TaxOrder=&foodallerg=all&bioname=.
- Blank S. Marker allergens in Hymenoptera Venom Allergy - Characteristics and potential use in precision medicine. Allergo J Int. 2020.
- Vachova M, Panzner P, Kopac P, Bidovec Stojkovic U, Korosec P. Routine clinical utility of honeybee venom allergen components. J Allergy Clin Immunol Pract. 2018;6(6):2121-3 e1.