Puissant-Lubrano Bénédicte, Puissochet Sylvain, Congy-Jolivet Nicolas, Chauveau Dominique, Decramer Stéphane, Garnier Arnaud, Huart Antoine, Kamar Nassim, Ribes David, Blancher Antoine
Laboratoire d'Immunologie, CHU de Toulouse, Hôpital Rangueil, Toulouse, France; Laboratoire d'Immunogénétique Moléculaire, Université Paul Sabatier, Toulouse 3, Toulouse, France.
Laboratoire d'Immunogénétique Moléculaire, Université Paul Sabatier, Toulouse 3, Toulouse, France.
Clin Immunol. 2017 Oct;183:1-7. doi: 10.1016/j.clim.2017.06.007. Epub 2017 Jun 21.
Eculizumab is a monoclonal anti-C5 antibody used in the treatment of atypical hemolytic uremic syndrome (aHUS). We monitored complement inhibition in 16 eculizumab-treated patients suffering from HUS or transplant rejection (not aHUS patients). Blood samples were obtained one to four weeks after the last eculizumab injection. We observed that eculizumab efficiently blocked the terminal pathway (TP) through classical pathway (CP) activation measured by kinetic hemolytic assay (HA) (<10%) but incompletely blocked the TP through alternative pathway (AP) activation measured by rabbit (APH50>23%) or chicken erythrocytes HA (AP100>15%). Conversely, functional ELISA revealed a complete blockade of TP through AP activation in all patients (<10%). C5a and sC5b9 levels were not correlated with residual APH50 or AP100. Similar results were obtained after in vitro addition of increasing amounts of eculizumab to a control serum (in vitro APH50>60% and AP100>20%). We also showed that ELISA was less sensitive than HA.
依库珠单抗是一种单克隆抗C5抗体，用于治疗非典型溶血尿毒综合征（aHUS）。我们监测了16例接受依库珠单抗治疗的溶血尿毒综合征（HUS）或移植排斥反应患者（非aHUS患者）的补体抑制情况。在最后一次注射依库珠单抗后1至4周采集血样。我们观察到，依库珠单抗通过动力学溶血试验（HA）测量的经典途径（CP）激活有效地阻断了终末途径（TP）（<10%），但通过兔源（APH50>23%）或鸡红细胞HA（AP100>15%）测量的替代途径（AP）激活未完全阻断TP。相反，功能性ELISA显示所有患者通过AP激活对TP的阻断是完全的（<10%）。C5a和sC5b9水平与残余的APH50或AP100不相关。在对照血清中体外添加越来越多的依库珠单抗后也获得了类似结果（体外APH50>60%，AP100>20%）。我们还表明ELISA比HA敏感性更低。
