Undressing DReSS as p-i mediated disease

Area of Science:

• Immunology
• Pharmacology
• Toxicology

Background:

• Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a severe T cell-mediated hypersensitivity.
• The underlying mechanism of DReSS has been poorly understood, leading to diagnostic and therapeutic challenges.

Purpose of the Study:

• To elucidate the mechanism of T cell activation in DReSS.
• To propose a unifying explanation for DReSS pathogenesis.
• To identify key factors influencing DReSS development.

Main Methods:

• The study focuses on the p-i (pharmacological interaction with immune receptors) mechanism.
• Analysis of drug-target interactions involving T cell receptors (TCR) and/or HLA molecules.
• Evaluation of drug concentration, duration of therapy, and HLA/TCR binding affinity.

Main Results:

• T cells in DReSS are activated via the p-i mechanism, involving off-target drug binding to TCR and/or HLA.
• High drug doses, prolonged administration (>7 days), and high affinity binding enhance p-i stimulation.
• This leads to delayed but profound immune activation, progressing through four distinct phases.

Conclusions:

• The p-i concept offers a unifying explanation for DReSS.
• Understanding drug concentration, therapy duration, and HLA affinity is crucial for risk assessment.
• This knowledge can improve early diagnosis, management, and prevention strategies for DReSS.