Neo-antigens for the serological diagnosis of IgE-mediated drug allergic reactions to antibiotics cephalosporin, carbapenem and monobactam

Autores de IIS La Fe

• Sergi Morais Ezquerro

  Autor

• Ángel Maquieira Catalá

  Autor

Participantes ajenos a IIS La Fe

• Pena-Mendizabal, E

Grupos

• Unidad Mixta de Investigación en Nanomedicina y Sensores

Abstract

New antigens deriving from -lloyl and -llanyl, major and minor determinants, respectively, were produced for beta-lactam antibiotics cefuroxime, cefotaxime, ceftriaxone, meropenem and aztreonam. Twenty beta-lactam antigens were produced using human serum albumin and histone H1 as carrier proteins. Antigens were tested by multiplex in vitro immunoassays and evaluated based on the detection of specific IgG and IgE in the serum samples. Both major and minor determinants were appropriate antigens for detecting specific anti-beta-lactam IgG in immunised rabbit sera. In a cohort of 37 allergic patients, we observed that only the minor determinants (-llanyl antigens) were suitable for determining specific anti-beta-lactam IgE antibodies with high sensitivity (<0.01 IU/mL; 24 ng/L) and specificity (100%). These findings reveal that not only the haptenisation of beta-lactam antibiotics renders improved molecular recognition events when the 4-member beta-lactam ring remains unmodified, but also may contribute to develop promising minor antigens suitable for detecting specific IgE-mediated allergic reactions. This will facilitate the development of sensitive and selective multiplexed in vitro tests for drug-allergy diagnoses to antibiotics cephalosporin, carbapenem and monobactam.