Allopurinol Sodium

Allopurinol is metabolized to its active metabolite oxypurinol, which serves as the primary driver of CD8+ T cell-mediated hypersensitivity reactions in susceptible individuals. Oxypurinol interacts with peptide/HLA complexes through a labile, non-covalent binding mechanism that does not require intracellular antigen processing. This interaction follows the pharmacological interaction with immune receptors concept, where the drug metabolite forms an immunogenic complex directly at the cell surface. The resulting T cell activation leads to oligoclonal expansions of drug-reactive T cells, with private clonotypic profiles observed in both resolved hypersensitivity cases and drug-naïve healthy donors. These reactive T cells exhibit a proinflammatory immunophenotype similar to T cells described during active Stevens-Johnson syndrome or toxic epidermal necrolysis.

Fig. 1 Allopurinol (ALP) drives oligoclonal expansions of drug-reactive CD8+ T cells via p-i interaction. (Mifsud N A.; et al. 2023)