Our main topic of interest is drug allergy. Whereas our adaptive immune system is supposed to recognize large molecular structures from microorganisms for immune protections, it can happen that our immune system becomes activated by small molecular compounds like chemical drugs. In severe cases the activation of the immune system becomes out of control and puts the life of the affected individual at stake. In our research we try to understand the cellular and molecular mechanisms involved in drug allergic reactions.

HLA associated drug hypersensitivity reactions
Some genetic factors (HLAs) have been identified to be associated with hypersensitivity reactions to particular drugs. For example Abacavir, an effective drug used in the treatment of HIV infection causes hypersensitivity reactions only in individuals carrying the HLA-B*57:01 allele (~5% of the European population). On this topic, we are developing models to investigate the interactions between HLA molecules, the drug and the immune T cell receptor.

Metamizole induced agranulocytosis
Metamizole is a painkiller with antipyretic properties. Although this drug is very effective, its safety profile is not totally secure. In rare cases, treatment with metamizole can lead to life-threatening agranulocytosis. We aim to identify whether the adaptive immune system could be activated by metamizole and then play a cytotoxic role toward granulocyte precursor cells.

Link between T cell activation mechanisms and allergic symptoms
In drug hypersensitivity reactions, drug-reacting T cells can often be found in the blood of allergic patients or in the lesions directly. Two different models can explain the activation of T cell by drug: the hapten model for which antigenic peptides are covalently modified by the drug or its metabolites; or the pi model (Pharmacological Interaction), for which interactions are mediated by van der Waals interactions only and so no covalent modifications are necessary. Until now, the clinical relevance of each model is not clear. We are running a study investigating whether the broad range and the severity of the symptoms of drug allergy (urticarial, maculo-papular erythema, Steven-Johnson Syndrome, DRESS) can be correlated with the activation mechanism of involved drug-reacting T cells.

Publication


Mitarbeitende/Team

Daniel Yerly, PhD, Wissenschaftlicher Assistant
Klara Eriksson, Laborantin
Dolores Dina, Doktorandin