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

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.

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.

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.

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.