Return to Contents in this Issue



Hypersensitivity Reactions to β-Lactams: Relevance of Hapten-Protein Conjugates


Ariza A1, Mayorga C1,2, Fernández TD1, Barbero N3,4, Martín-Serrano A1,3, Pérez-Sala D5, Sánchez-Gómez FJ5, Blanca M2, Torres MJ2*, Montañez MI1,3*

1Research Laboratory, IBIMA, Regional University Hospital of Malaga, UMA, Malaga, Spain
2Allergy Unit, IBIMA, Regional University Hospital of Malaga, UMA, Málaga, Spain
3BIONAND—Andalusian Centre for Nanomedicine and Biotechnology, Malaga, Spain
4Department of Organic Chemistry, Faculty of Sciences, IBIMA, University of Malaga, Malaga, Spain
5Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain
*Both authors contributed equally to this work.

J Investig Allergol Clin Immunol 2015; Vol. 25(1): 12-25



β-Lactams (BL) are the drugs most frequently involved in allergic reactions. They are classified according to their chemical structure as penicillins, cephalosporins, monobactams, carbapenems, and clavams. All BL antibiotics have a BL ring that is fused to a 5-member or 6-member ring (except in monobactams) and has 1, 2 or 3 side chains (except in clavams). Differences in chemical structure mean that a wide range of BLs are recognized by the immune system, and patients may experience clinical reactions to one BL while tolerating others. Diagnosis is based on skin and in vitro testing, although both display low sensitivity, possibly because they are based on drugs or drug conjugates that are not optimally recognized by the immune system. BLs are haptens that need to bind to proteins covalently to elicit an immune response. These drugs have a high capacity to form covalent adducts with proteins through nucleophilic attack of amino groups in proteins on the BL ring. Allergenic determinants have been described for all BLs, although benzylpenicillin is the most widely studied. Moreover, formation of BL-protein adducts is selective, as we recently demonstrated for amoxicillin, which mainly modifies albumin, transferrin, and immunoglobulin heavy and light chains in human serum. Given the complexity of BL allergy, understanding the immunological mechanisms involved and optimization of diagnostic methods require multidisciplinary approaches that take into account the chemical structures of the drugs and the carrier molecules, as well as the patient immune response.

Key words: Betalactams. Hapten. Carrier. Proteins. IgE.