Cell-mediated immunity in allopurinol-induced hypersensitivity

Allopurinol may induce severe hypersensitivity characterized by hepatitis, interstitial nephritis, and skin rash. The mechanisms for this hypersensitivity syndrome are incompletely elucidated. Immunologic studies were performed on tissue and peripheral blood lymphocytes from a patient with allopurinol hypersensitivity. Immunohistochemistry was performed on sections of the liver biopsy utilizing monoclonal antibodies for T and B lymphocytes. Peripheral blood lymphocyte immunophenotyping by flow cytometry and peripheral blood lymphocyte stimulation studies with either allopurinol or oxypurinol measured as tritiated thymidine uptake were performed in the hypersensitive patient and compared to a group of six patients treated with allopurinol without hypersensitivity and eight normal control patients. Additional single- and dual-color immunophenotyping by flow cytometry of oxypurinol-stimulated lymphocytes was performed in the hypersensitive patient and compared to normal controls. The liver biopsy demonstrated predominantly a T lymphocyte infiltrate. The number of peripheral blood lymphocytes expressing activation antigens was significantly greater in the hypersensitive patient compared to that of both control groups. Lymphocytes from the hypersensitive patient were moderately stimulated by allopurinol and markedly stimulated by oxypurinol compared to both control groups. Oxypurinol-stimulated lymphocytes from the hypersensitive patient demonstrated enhanced expression of activation antigens compared to unstimulated lymphocytes from this patient and normal controls. These studies suggest that cell-mediated immunity directed toward allopurinol and more importantly to its oxypurinol metabolite is involved in the pathogenesis of allopurinol-induced hypersensitivity.