Diclofenac‐induced antibodies against red blood cells are heterogeneous and recognize different epitopes

Abstract

BACKGROUND: Diclofenac (DCF) is a widely used nonsteroidal anti-inflammatory drug implicated as a cause of immune hemolytic anemia. Drug derivatives have been suggested to be an important—or probably the primary—immunizing agent in drug-induced immune reactions. A systematic evaluation of 12 patients with DCF-induced immune hemolysis is reported. STUDY DESIGN AND METHODS: All sera samples were evaluated with standard serologic tests for the detection of red blood cells (RBCs) and platelet (PLT) antibodies in the presence of DCF, DCF-urine (DCF-U), and five chemically defined metabolites. RESULTS: Twelve patients’ sera samples reacted with DCF-U, but only 9 reacted with DCF. When derivatives were tested, no metabolite was recognized by all sera samples (although 4′-OH-DCF was recognized by 11/12), and no metabolite remained unrecognized. As demonstrated with Rh_null cells, the Rh complex may represent an important, but not the only, target protein for which drug-dependent antibodies are specific. PLT-reactive antibodies were not detectable. CONCLUSION: There is evidence that patients with DCF-induced immune hemolysis produce a broad spectrum of anti-DCF/RBC antibodies. 4′-OH-DCF seems to represent the most immunogenic metabolite. Nevertheless, all patients’ sera samples contain a mixture of antibodies that recognize several and distinguishable epitopes. These epitopes consist of different drug metabolites and a target protein on the RBC surface, which appears to be the Rh complex in many, but not in all, cases. Additional target proteins remain to be identified.