Dendrimeric Antigens for Passive Mast Cell Activation in the Evaluation of Amoxicillin Allergy
Year: 2026
Type: article
Abstract: BACKGROUND: Amoxicillin (AX) is frequently implicated in immediate IgE-mediated allergic reactions. Diagnosis is challenging, highlighting the need for new approaches enhancing in vitro sensitivity and specificity. Engineered nanostructures can mimic immunological recognition of hapten-carrier conjugates, offering a strategy to improve diagnostic accuracy. METHODS: Dendrimeric Antigens (DeAns), with controlled size (1st-5th generation) and multivalent AX determinants (8-128 units, respectively), were synthesized for in vitro immunological evaluation. In vitro IgE recognition was studied by competitive radio-immunoassay. Allergenic activity was evaluated in mouse bone marrow-derived mast cells (MC) sensitized with mouse anti-AX IgE monoclonal antibody and humanized RBL-2H3 (huRBL-2H3) and LUVA cells sensitized with sera from β-lactam-allergic subjects and tolerant controls, measuring degranulation in response to DeAns stimulation. RESULTS: Five different DeAns were obtained as pure compounds. All DeAns were recognized by AX-sIgE. A clear size-dependent activation pattern was observed in the three cell models: lower-generation (1st-2nd) DeAns failed to induce degranulation, whereas DeAns of bigger size (3rd-5th generation) triggered significant, dose-dependent activation. Notably, no activation was observed in tolerants and unsensitized cells or with blank dendrimers. In patient-sera assays, the passive MC activation test (pMAT) with DeAns provided complete diagnostic discrimination, with activation restricted to AX-allergic patients. CONCLUSIONS: DeAns are effective platforms for investigating effector cell activation in AX allergy. By fine-tuning structural attributes-size and multivalence-we reveal the promising utility of DeAns in pMAT that leverage commercial cell lines and patient sera. This approach could address key limitations of β-lactam allergy diagnostics, enabling more reliable and standardized in vitro testing.
Source: Allergy
DOI: 10.1111/all.70250
Institutions: Andalusian Centre for Nanomedicine and Biotechnology, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Hospital Regional Universitario de Málaga, Consejo Superior de Investigaciones Científicas, Instituto de Investigación en Ciencias de la Alimentación, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,300
Awards: G1105844351, G1175115578, G1855990336, G1962745078, G201340151, G2262748287, G2309174360, G2601397997, G2660406951, G2672435700, Aplicación de nanoarquitecturas sintéticas al estudio de los mecanismos de activación del basófilo y al diagnóstico en reacciones alérgicas a amoxicilina, G300979063, G3117242519, Nuevas aproximaciones aplicadas al diagnóstico de alergia a fármacos: Desarrollo de nanoestructuras que incorporan ligando TLR y determinantes antigénicos de antibióticos betalactámicos., G3480869486, G3681454997, Nanoarquitecturas altamente eficientes para un entrecruzamiento eficaz de la IgE en mastocitos y basófilos. Aplicación al diagnóstico de reacciones alérgicas a amoxicilina y ácido clavulánico., G4004671811, G4042783231, G425668148, G430777504, G4833715428, Optimización diagnóstica en alergia a betalactámicos: de la estandarización y racionalización de las pruebas in vivo, al desarrollo de test in vitro innovadores basados en nanotecnología y metabolómica., G491712853, Nanomedicine Doctoral Programme, G4937468798, G5080475149, G5167452342, G5195188938, G5421974903, G5781591375, G5997385541, G683931746, G7084143925, Nanodiagnóstico para la hipersensibilidad a betalactámicos, G7805626310, G7834924252, G7863371703, G7892477181, G8347645112, G8497050386, G8696694383, G871842226, G8777962859, G8824911526, En busca del diagnóstico correcto de la alergia a betalactámicos: desde la validación de una herramienta de estratificación del riesgo a un endotipado preciso, G8920660035, G8988427660, G99296377
OpenAlex ID: W7128607652