Study of Specific IgE Recognition of New Potential Synthetic Antigenic Determinants for α-Amino-Cephalosporins
Saturday, March 3, 2018
South Hall A2 (Convention Center)
Angela Martin-Serrano Ortiz, Cristobalina Mayorga, PhD, Esther Barrionuevo, MD, PhD, Alba Rodriguez-Nogales, PhD, Ezequiel Perez-Inestrosa, PhD, Maria Jose Torres Jaén, MD, PhD, Maria Isabel Montañez, PhD
RATIONALE: Cephalosporins are, after penicillins, the most important betalactam inductor of immediate allergic reactions. Due to difficulties for studying the structure of cephalosporin-protein conjugates, the antigenic determinants of cephalosporins are still unknown. This fact has hampered the existence of in vitro tests with enough sensitivity to detect allergy to cephalosporins. The objective was to synthesize pyrazinone-like derivatives of two aminocephalosporins as potential antigenic determinants and evaluate their specific IgE recognition.

METHODS: Structures derived from cefaclor and cefadroxil, in accordance with our aminocephalosporins degradation hypothesis, were synthesized using Ugi/Desprotection/Cyclize strategy. These new aminocephalosporins derivatives, along with other previously reported synthetic antigenic determinants, were immunologically evaluated by Radio-Allergo-Sorbent-Test (RAST) inhibition at two concentrations (100 and 10 mM) using sera from 21 patients (10 allergic to cefaclor and 11 to amoxicillin).

RESULTS: RAST inhibition, using sera allergic to cefaclor, was significant at the maximum concentration in a 50% of the patients for pyrazinone-like structure and in a 30% for previously reported antigenic determinant. RAST inhibition, using sera allergic to amoxicillin, was significant at the maximum concentration in a 45% of the patients for pyrazinone-like structure and in a 64% for the previously reported synthetic determinant.

CONCLUSIONS: The new synthetic determinants allowed specific IgE detection, improving the immunoassay sensitivity compared with the previously proposed antigenic determinants of cefaclor. These findings situate us a step closer to the elucidation of the antigenic determinant structures involved in the allergy to aminocephalosporins.