Casadevall Nicole
Service d'Hématologie Biologique, Hôtel-Dieu, Paris, France.
Nephrol Dial Transplant. 2002;17 Suppl 5:42-7. doi: 10.1093/ndt/17.suppl_5.42.
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.
重组人促红细胞生成素（rHuEPO）已成功用于纠正慢性肾衰竭贫血超过12年。在此期间，仅报道过3例患者出现中和性抗促红细胞生成素抗体。然而，在过去2年中，有21例接受rHuEPO治疗的患者因对重组激素突然产生耐药性以及出现需要输血的纯红细胞再生障碍而被转诊至我们实验室。这些患者呈现的临床症状表明他们可能产生了中和性抗促红细胞生成素抗体。在所有病例中，均有证据表明存在强效中和抗体。首先检测了患者血清中和促红细胞生成素以及抑制正常骨髓红细胞集落形成的能力。然后通过使用天然、去糖基化和变性的促红细胞生成素对放射性标记的促红细胞生成素进行免疫沉淀，直接证实了抗促红细胞生成素抗体的存在。这些患者产生抗促红细胞生成素抗体的原因尚不清楚，尽管显然与rHuEPO治疗有关。一个合理的解释可能是生产过程中的轻微改变导致了所生产激素的某种抗原性。然而，这一假设尚未得到证实。迅速检测此类抗体似乎对于限制抗体滴度和加速恢复很有必要。16例患者在接受免疫抑制治疗后抗体消失。
