Drug hypersensitivity reaction is an unexpected immune response that may be experienced after taking a medication. The symptoms may range from mild to severe or even life-threatening. This type of response is more likely with newer drugs which have not yet had all possible side-effects discovered.
Although this type of reaction may be rare, the seriousness of the symptoms cannot be ignored. New drugs may need to be removed from the market when such severe side-effects come to light. Why some drugs activate a drastic immune response is not fully understood. Research to discover how to predict, prevent, or control such symptoms will be useful to develop better drugs.
A recent study at the FDA attempted to gain some understanding of the hypersensitivity reaction. The work focused on abacavir, an anti-retroviral HIV drug, which is known to commonly induce such undesired reaction. The severe immune response sometimes experienced with abacavir is known to be associated with a specific genetic variation, which is generally screened for prior to use.
In the lab, genetically altered mice were generated to produce the drug-hypersensitive variation. The mice were treated with abacavir for 8 days. Cellular and transcriptomic responses to the treatment were measured.
The research uncovered novel immune mechanisms driven by this molecule, related to inflammatory triggers involving Treg cells and CD4+ cells. Critical pathways that may be useful targets for therapy were identified in this study. Further research and understanding of these targets will help to prevent and manage the severe drug hypersensitivity reactions. This will reduce the risk and increase the benefit of drugs with this side-effect.
Cardone M, Baghdassarian H, Khalaj M, et al. Insights into regulatory T-cell and type-I interferon roles in determining abacavir-induced hypersensitivity or immune tolerance. Front Immunol. 2025 Jun 6:16:1612451. PMID: 40547023