INA (= In vitro detection of drug allergy) – Analysis of differential gene and protein expression for the in vitro detection of drug allergy

Head of consortium:

BfArM (Prof. Dr. Bernhardt Sachs, Dr. Andreas Glässner, Dr. Christine Krämer)

Consortium partners:

University Hospital RWTH Aachen, Clinic for Dermatology and Allergology (Univ.-Prof. Dr. Amir Yazdi)

Life & Brain GmbH (Ltd.) Bonn (Prof. Dr. Markus Nöthen)

Leibniz Institute for Analytical Sciences – ISAS – e.V. Dortmund (Prof. Dr. Albert Sickmann)

Drug allergies are a particularly relevant form of allergy, the frequency of which is likely to increase further due to the demographic change. The diagnosis of drug allergies is currently based on:

  1. Medical history and classification of the clinical phenotype of the reaction.
  2. In vivo tests: prick test and intracutaneous test. These skin tests can be time consuming, have limited sensitivity and are standardized for few active ingredients only.
  3. In vitro tests (laboratory tests): These consist of i) methods to detect specific antibodies (IgE) in immediate-type reactions which are available for a few drugs only and ii) cellular test systems such as the lymphocyte transformation test (LTT). However, the LTT in its traditional form (read-out parameter: 3H-thymidine incorporation into the DNA of the proliferating cells) is rather cumbersome and thus unsuitable for routine diagnostics.
  4. Provocation tests: These tests bear the risk of an allergic reaction and are therefore often rejected by patients. They are contraindicated, if a severe allergic reaction had occurred in the medical history.

In summary, the currently available methods to diagnose drug allergy are limited. This is in contrast to a great need for a reliable method appropriate to be used in routine diagnostics. This method should be safe, not stressful for patients, and not too time consuming. In this respect, in vitro tests are particularly suitable as they only require a blood sample to be taken from the patient and provide the opportunity to test more than one suspected drug.

Aims of the project:
The overall aim of the project is to investigate – by means of innovative, state-of-the art methods – basic principles which could facilitate the development of an in vitro diagnostic test suitable for routine diagnosis in drug allergy. To this end, the differential gene and protein expression of peripheral mononuclear cells (PBMCs) of drug-allergic patients after in vitro stimulation with the suspected drug will be analysed and compared to those of non-allergic test persons.

Project description and methodology:
Patients with confirmed drug allergy as well as control persons without drug allergy will be investigated using the drug in question. PBMCs are isolated from blood and cultured with the drug in question. This is followed by the genome- and proteome-wide analysis of the gene and protein expression in the PBMCs with respect to suitable target genes and/or their transcription products. After suitable read-out parameters have been identified in the first phase of the project, these will be investigated with a larger number of patients in the second phase of the project.

The main work steps of this project are (lead partners in brackets):

  1. recruitment of patients with confirmed drug allergy and control persons without drug allergy (Clinic for Dermatology and Allergology, University Hospital RWTH Aachen)
  2. isolation of the PBMCs of the patients and control persons and co-incubation of these PBMCs with the drug in question followed by isolation of their RNA (Federal Institute for Drugs and Medical Devices, BfArM)
  3. genome- and proteome-wide analysis of differential gene and protein expression (Life & Brain GmbH (Life & Brain); Leibniz Institute for Analytical Sciences (ISAS)
  4. identification of suitable target genes and/or their transcription products as read-out parameters (Life & Brain, ISAS, BfArM)


  1. Sachs B, Glässner A. Editorial – Special Issue on in vitro detection of drug allergy. Journal of Immunological Methods. Vol. 493; June 2021; 113004.
  2. Sachs B, Fatangare A, Sickmann A, Glässner A. Lymphocyte transformation test: History and current approaches. Journal of Immunological Methods. Vol. 493; June 2021; 113036.
  3. Fatangare A, Glässner A, Sachs B, Sickmann A. Future perspectives on in-vitro diagnosis of drug allergy by the lymphocyte transformation test. Journal of Immunological Methods. Vol. 495; August 2021; 113072. https://www.sciencedirect com/science/article/pii/S0022175921001174

This project is funded by the European Regional Development Fund (ERDF) and the State of NRW (Leitmarkt) as well as by resources of the participating partners. Funding period: 2020 -2022.