Which Drug has elicited a presumable immune mediated adverse reaction?

ADR-AC will advise which tests make sense and performs them
(or provides help to establish them). We use human cells in vitro.

• Modified lymphocyte transformation tests: >10.000 standard LTTs have been performed over the last 20 years by the drug allergy group at the Inselspital: this experience is a good basis to apply this test in an optimal way to drug allergy diagnosis.
• We have developed new tests to detect drug reactive T cells by other methods (cytokine synthesis, upregulation of activation markers, etc), which can be applied as well. Modifications do also include tests to detect cytotoxic CD8+ T cells reactive to drugs and basophile activation tests, relying on drug specific IGE. These tests are suitable to identify the relevant drug in drug hypersensitivity, be it in phase 1-3 studies or with drugs already on the market.
• Phase 1-3 accompanying studies: To control the sensitizing potential of a drug during drug development (phase 1-3 studies), some accompanying tests may be indicated to clarify the situation (e.g., if preclinical studies gave some indication of a sensitizing potential of a drug).
• Cross-reactivity analysis can be determined by proliferation of PBMC. For some drug groups T cell clones and TCR-transfected hybridomas are available, which would allow a more extensive analysis of cross-reactivity.
• Test to define the "sensitising" risk of a new drug are difficult. Some drugs may indeed sensitize and elecit an own, hapten specific immune reaction. Other drugs may not sensitize but reactivate peptide-specific T cells (= p-i concept). We are developing tests which analyse in vitro the stimulatory capacity in individual, HLA-typed PBMC, which have not been exposed to the drug previously. The sensitising potential of a drug will be determined based on drug specific activation, proliferation, cytokine synthesis, cytotoxicity etc. of the T-cells. Each compound – even if it is a metabolite – has to be tested and evaluated separately.
• Drug binding to T cell receptors TCR): The p-i concept was developed by W.J. Pichler in Bern: It implies that drug hypersensitivity reactions may start by drugs directly binding to TCR. We have developed a test for this TCR-drug binding. The read out reflects different biological functions and is thus also related to the affinity of drug-TCR reactions. It is based on the availability of hybridoma cells transfected with TCR – some of them broadly reactive.

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