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Eculizumab, a monoclonal antibody against the C5 component of complement, decreases hemolysis and thrombosis in congenital and acquired paroxysmal nocturnal hemoglobinuria (PNH). The agent is effective in almost all patients with this disorder.
To determine the cause of occasional eculizumab resistance, investigators conducted a manufacturer-supported study of PNH in 11 Japanese patients and 1 Argentinean patient of Asian ancestry. All patients had persistently elevated lactic dehydrogenase and hemolysis despite therapeutic blood levels of eculizumab.
Genetic analysis revealed that the patients resistant to eculizumab had a heterozygous mutation at the C5 binding site; in the Japanese patients, the mutation coded for an Arg885His polymorphism…