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在健康献血者的血浆中发现了针对化疗药物奥沙利铂的抗体。

Antibodies to oxaliplatin, a chemotherapeutic, are found in plasma of healthy blood donors.

机构信息

American Red Cross, Southern California Blood Services Region, Pomona, CA91768, USA.

出版信息

Transfusion. 2011 Aug;51(8):1740-4. doi: 10.1111/j.1537-2995.2010.03040.x. Epub 2011 Feb 8.

DOI:10.1111/j.1537-2995.2010.03040.x
PMID:21303372
Abstract

BACKGROUND

Oxaliplatin is one of the platinum chemotherapeutics that includes cisplatin and carboplatin. Antibodies to all three drugs have caused immune hemolytic anemia (IHA). In an investigation of oxaliplatin-induced IHA, the negative plasma control agglutinated oxaliplatin-coated red blood cells (RBCs). Previous preparations of this control had not agglutinated oxaliplatin- or cisplatin-coated RBCs.

STUDY DESIGN AND METHODS

Drug-coated RBCs, prepared by incubating 1/10th volume of RBCs with 1 mg/mL drug in phosphate-buffered saline for 1 hour at 37°C, were incubated with plasma from random blood donors and patients. Plasma was treated with dithiothreitol to determine the immunoglobulin class. Hapten inhibition was performed by incubating plasma with solutions of oxaliplatin or cisplatin.

RESULTS

Nineteen of 121 (16%) donors' plasma samples agglutinated oxaliplatin-coated RBCs; 7 of 102 (7%) donors' plasma samples agglutinated cisplatin-coated RBCs. Two of 50 (4%) patients' samples agglutinated oxaliplatin-coated RBCs. The agglutinin was immunoglobulin M and inhibited by oxaliplatin and cisplatin.

CONCLUSION

An agglutinin reactive with oxaliplatin-coated RBCs was found in 16% of donors' and 4% of patients' samples. Inhibition by oxaliplatin and cisplatin indicates the antibody may be directed to platinum. The presence of this antibody in healthy individuals may be related to the increasing environmental presence of platinum in air and soil as a byproduct of automobile catalytic converters and pharmaceuticals in our water and food chain. This antibody in individuals without IHA suggests that testing untreated and enzyme-treated RBCs in the presence of a solution of drug may be the best method to investigate IHA caused by drugs in the platinum family.

摘要

背景

奥沙利铂是铂类化疗药物之一,包括顺铂和卡铂。所有三种药物的抗体都会导致免疫性溶血性贫血(IHA)。在对奥沙利铂引起的 IHA 进行调查时,阴性血浆对照会凝集奥沙利铂包被的红细胞(RBC)。以前制备的这种对照物不会凝集奥沙利铂或顺铂包被的 RBC。

研究设计和方法

通过将 RBC 的 1/10 体积与 1 mg/mL 药物在磷酸盐缓冲盐水(pH7.4)中于 37°C 孵育 1 小时来制备药物包被的 RBC,然后将这些 RBC 与来自随机献血者和患者的血浆孵育。用二硫苏糖醇处理血浆以确定免疫球蛋白类别。通过将血浆与奥沙利铂或顺铂溶液孵育来进行半抗原抑制。

结果

121 份供体血浆样本中的 19 份(16%)凝集奥沙利铂包被的 RBC;102 份供体血浆样本中的 7 份(7%)凝集顺铂包被的 RBC。50 份患者样本中的 2 份(4%)凝集奥沙利铂包被的 RBC。凝集素为免疫球蛋白 M,可被奥沙利铂和顺铂抑制。

结论

在 16%的供体和 4%的患者样本中发现了与奥沙利铂包被 RBC 反应的抗体。奥沙利铂和顺铂的抑制表明该抗体可能针对铂。在健康个体中存在这种抗体可能与空气中和土壤中铂作为汽车催化转化器的副产品以及我们水和食物链中的药物的环境存在增加有关。在没有 IHA 的个体中存在这种抗体表明,在存在药物溶液的情况下测试未经处理和酶处理的 RBC 可能是研究铂类药物引起的 IHA 的最佳方法。

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