Monitoring Ravulizumab effect on complement assays
Monitoring Ravulizumab effect on complement assays
复制标题
DOI：
10.1016/j.jim.2020.112944
复制
发表时间：
2021-02-02
影响因子：
2.2
通讯作者：
Murray, David L.
中科院分区：
文献类型：
--
作者：
Willrich, Maria A., V;Ladwig, Paula M.;Murray, David L.
Ravulizumab是一种新的C5抑制剂治疗性单克隆抗体，半衰期比依库珠单抗更长。通过依库珠单抗监测完全补体阻断允许在特定环境中进行个性化治疗。预期ravulizumab具有类似作用。Ravulizumab与依库珠单抗具有4个不同的氨基酸，其允许对FcRn免疫球蛋白受体的更大亲和力并改变分子对C5的亲和力。在这里，我们调查了传统上用于监测依库珠单抗的补体阻断的临床实验室测试是否适合于监测由ravulizumab引起的补体阻断。将具有已知正常补体活性的去识别血清样品掺入增加量的ravulizumab，从0到1000 μ g/mL。使用脂质体方法（和子Diagnostics）测量经典途径功能（CH 50）和C5功能显示从50 μ g/mL的ravulizumab开始>50%的补体抑制，但未实现>95%的补体活性抑制，在700 μ g/mL下的残留测量值为11%。相反，使用ELISA（AH 50，Wieslab）测量旁路途径功能显示，在50 μ g/mL的ravulizumab下旁路途径功能抑制为80%，在200 μ g/mL下> 95%，这与ravulizumab >175 μ g/mL的预期治疗浓度一致。如果在患者血清中复制，AH 50可能是一个合适的治疗监测工具。
Ravulizumab is a new C5 inhibitor therapeutic monoclonal antibody with a longer half-life than eculizumab. Monitoring complete complement blockade by eculizumab has allowed personalized therapy in specific settings. Similar action is expected with ravulizumab. Ravulizumab has 4 different amino acids from eculizumab, which allow greater affinity for the FcRn immunoglobulin receptor and change the affinity of the molecule for C5. Here we investigate if clinical lab tests traditionally used to monitor complement blockade for eculizumab are appropriate for monitoring complement blockade caused by ravulizumab.De-identified serum samples with known normal complement activity were spiked with increasing amounts of ravulizumab, from zero to 1000 mu g/mL. Measurement of classical pathway function (CH50) and C5 function using a liposome method (Wako Diagnostics) showed >50% complement inhibition starting with 50 mu g/mL of ravulizumab, but inhibition >95% of complement activity was not achieved, with residual measurements of 11% at 700 mu g/mL. In contrast, measurement of alternative pathway function using an ELISA (AH50, Wieslab) showed alternative pathway function inhibition of 80% at 50 mu g/mL of ravulizumab and > 95% at 200 mu g/mL, which is consistent with expected therapeutic concentrations of ravulizumab >175 mu g/mL. If replicated in patient sera, AH50 could be a suitable therapeutic monitoring tool.