In their report (1) Xiaoxia Jiang et al. studied the role of phagocytes in drug metabolism by measuring the anti-proliferative effect of products from drug-exposed neutrophils. They did not, however, present physicochemical evidence for reactive drug metabolites reportedly generated by these cells and did not provide evidence for an immunostimulatory effect of these products that might lead to drug-induced lupus. We and others demonstrated specific immune reactions to defined metabolites of lupusinducing drugs. Unlike the parent drugs or unreactive metabolites, the reactive metabolites tested proved immunogenic for T cells and, in a T cell-dependent fashion, activated B cells. Thus, the parent drugs procainamide (PA) (2), propylthiouracil (PTU) (3) (both of them studied by jiang et al.), and gold(I) thiomalate (3) all were shown not to be immunogenic for T cells, and the same results were obtained for the unreactive metabolite N-acetyl-PA (1). In contrast, the reactive intermediates of these drugs, hydroxylamino-PA (2), PTU-sulfonate (3), and gold(III) (4,5)
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