New Insights of Biomarkers in IgE and Non-IgE-Mediated Drug Hypersensitivity

  • Cristobalina MayorgaEmail author
  • R. Muñoz-Cano
  • A. Rodríguez-Nogales
  • R. Fernandez-Santamaría
  • T. D. Fernandez
Drug Allergy (C Mayorga, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Drug Allergy


Background Drug hypersensitivity reactions (DHRs) occurring less than 6 h after the drug intake are named immediate reactions. They include allergic reactions, and pseudo-allergic or non-allergic reactions, and despite their similar clinical manifestations, the underlying mechanism is different. Its identification is essential for their management. In IgE-mediated-DHRs, the best biomarker is drug-specific IgE, which can be determined by in vivo and in vitro tests. Identifying the culprit drug is critical for the design of avoidance strategies and the recommendation of safe alternatives for future treatments.

Recent findings It has been suggested the existence of other mechanisms beyond IgE and related with the drug interaction with MRGPRX2 or IgG receptors, or mediated by their effect on some enzymes. However, the lack of a clear biomarker for characterizing them, together with the difficulty of predicting cross-reactivity, makes the management of non-allergic reactions very complex.

Desensitization is standard intervention in allergic patients who need the drug. It is successful in IgE-mediated DHRs but its value on non-IgE-mediated DHRs is not well-known.

Summary Further research is needed to identify the mechanism involved in DHRs considering that IgE and non-allergic reactions cannot be mutually exclusive and can happen simultaneously, increasing their severity. It is crucial the identification of biomarkers in non-allergic reactions.


Drug Hypersensitivity IgE Basophil Mast cells Anaphylaxis 



The present study has been supported by Institute of Health “Carlos III” of the Ministry of Economy and Competitiveness (grants cofunded by European Regional Development Fund (ERDF): PI15/01206, PI16/00696 and RETICS ARADYAL RD16/0006/0001, RD16/0006/0007; Andalusian Regional Ministry Health (grant: PI-0241-2016). CM holds a “Nicolas Monardes” research contract by Andalusian Regional Ministry Health: C-0044-2012 SAS 2013. RM-C is a recipient of a Juan Rodes fellowship (Carlos II Health Institute JR16/00016). TDF holds a “Ramon y Cajal” research contract from Ministry of Economy and Competitiveness (RYC-2013-13138).

Compliance with Ethical Standards

Conflict of Interest

Cristobalina Mayorga, R. Muñoz-Cano, A. Rodríguez-Nogales, R. Fernandez-Santamaría, and T. D. Fernandez declare that they have no conflicts of interest.

Human and Animal rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Cristobalina Mayorga
    • 1
    • 2
    • 3
    Email author
  • R. Muñoz-Cano
    • 4
    • 5
  • A. Rodríguez-Nogales
    • 1
  • R. Fernandez-Santamaría
    • 1
  • T. D. Fernandez
    • 1
  1. 1.Allergy Research GroupInstituto de Investigación Biomédica de Málaga-IBIMA. ARADyAL. Hospital CivilMálagaSpain
  2. 2.Allergy UnitHospital Regional Universitario de Málaga. ARADyAL Hospital CivilMálagaSpain
  3. 3.Nanostructures for Diagnosing and Treatment of Allergic Diseases Laboratory, Andalusian Center for Nanomedicine and Biotechnology-BIONANDMálagaSpain
  4. 4.Allergy Section, Neumology Department, Hospital Clinic, ARADyALUniversity of BarcelonaBarcelonaSpain
  5. 5.Clinical and Experimental Respiratory Immunoallergy (IRCE)August Pi i Sunyer Biomedical Research Institute (IDIBAPS)BarcelonaSpain

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