Antibodies against rHuEPO: native and recombinant.
Recombinant human erythropoietin (rHuEPO) has been used successfully to correct the anaemia of chronic renal failure for more than 12 years. During this time, neutralizing anti-erythropoietin antibodies have been reported in only three patients. However, during the last 2 years, 21 rHuEPO-treated patients have been referred to our laboratory because of sudden resistance to the recombinant hormone and a pure red cell aplasia requiring red blood cell transfusion. The clinical pattern presented by these patients suggested that they could have developed neutralizing anti-erythropoietin antibodies. In all cases, there was evidence of the presence of strong neutralizing antibodies. The ability of the patient's sera to neutralize erythropoietin and to inhibit erythroid colony formation from normal bone marrow was tested first. The presence of anti-erythropoietin antibodies was then demonstrated directly by immunoprecipitation of radiolabelled erythropoietin using native, deglycosylated, and denaturated erythropoietin. The reasons for anti-erythropoietin antibody production in these patients is unclear, although it is clearly related to the treatment with rHuEPO. A plausible explanation would be a slight modification in the production process leading to some antigenicity of the manufactured hormone. However, this hypothesis remains unproven. Prompt detection of such antibodies appears necessary to limit antibody titre and to speed recovery. Immunosuppressive treatment was followed by disappearance of the antibodies in 16 of the cases.
Casadevall
Nicole
N
Service d'Hématologie Biologique, Hôtel-Dieu, Paris, France. nicole.casadevall@htd.ap-hop-paris.fr
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D001323:Autoantibodies / Q000097:blood*; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D004921:Erythropoietin / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D011994:Recombinant Proteins
D001323:Autoantibodies; D011994:Recombinant Proteins; D004921:Erythropoietin