Noguchi A, Mukuria C J, Suzuki E, Naiki M
Department of Veterinary Science, National Institute of Health, Tokyo, Japan.
Nephron. 1996;72(4):599-603. doi: 10.1159/000188946.
Recombinant human erythropoietin (rHUEPO) was produced by Chinese hamster ovary cells and commercially distributed to hospitals by two pharmaceutical companies in Japan ('ESPO' by Kirin Brewery Co. Ltd., and Sankyo Co. Ltd., and 'EPOGIN' by Chugai Pharmaceutical Co. Ltd.) These products contained about 1% N-glycolylneuraminic acid (Neu5Gc) in total sialic acid content. Since humans do not synthesize Neu5Gc, successive injection of Neu5Gc-containing products was feared to lead to allergic-like symptoms. Therefore, serum levels of antibodies of Neu5Gc epitope in 90 patients who received repeated i.v. injections of ESPO or EPOGIN were determined by an enzyme immunoassay using Neu5Gc alpha 2-3Gal beta 1-4Glc-Cer, GM3(Neu5Gc), as an antigen and compared with those in 100 healthy persons. Either no or low antibody levels were detected in both groups with no significant difference. In 40 patients who received s.c. injections of ESPO or EPOGIN, serum HD antibody levels were determined before and after weekly therapeutic injections carried out for one to several months, but no significant elevations were detected in all patients. The above results indicated that therapeutic administration of rHuEPO to patients to patients with chronic renal failure is safe from allergic-like side effects associated with the production of Neu5Gc-specific antibodies, and it was concluded that Neu5Gc epitope of rHuEPO is minimally antigenic in humans.
重组人促红细胞生成素（rHUEPO）由中国仓鼠卵巢细胞产生，由日本两家制药公司在医院进行商业销售（麒麟啤酒株式会社和三共株式会社生产的“ESPO”，以及中外制药株式会社生产的“EPOGIN”）。这些产品的总唾液酸含量中含有约1%的N-羟乙酰神经氨酸（Neu5Gc）。由于人类不合成Neu5Gc，因此担心连续注射含Neu5Gc的产品会导致类似过敏的症状。因此，使用Neu5Gcα2-3Galβ1-4Glc-Cer、GM3（Neu5Gc）作为抗原，通过酶免疫测定法测定了90例接受ESPO或EPOGIN重复静脉注射患者的Neu5Gc表位抗体血清水平，并与100例健康人的水平进行了比较。两组均未检测到或仅检测到低水平抗体，无显著差异。在40例接受ESPO或EPOGIN皮下注射的患者中，在每周进行一至数月的治疗性注射前后测定血清HD抗体水平，但所有患者均未检测到显著升高。上述结果表明，对慢性肾功能衰竭患者进行rHuEPO治疗不会产生与Neu5Gc特异性抗体产生相关的类似过敏的副作用，得出的结论是rHuEPO的Neu5Gc表位在人类中的抗原性极低。
