Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, Paris, France; Equipe d'accueil 3518, Paris, France;
Laboratoire d'Immunologie, Assistance Publique-Hôpitaux de Paris, Hôpital Georges Pompidou, Paris, France; Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche Scientifiques 1138, Cordelier Research Center, Team: "Complement and Diseases," Paris, France;
Blood. 2015 Jan 29;125(5):775-83. doi: 10.1182/blood-2014-03-560540. Epub 2014 Dec 4.
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, which is effectively controlled with eculizumab, a humanized monoclonal antibody that binds complement protein 5 (C5). The residual functional activity of C5 can be screened using a 50% hemolytic complement (CH50) assay, which is sensitive to the reduction, absence, and/or inactivity of any components of the classical and terminal complement pathway. Little data exist on complement blockade during treatment. From 2010 to 2012, clinical data, hemolysis biomarkers, complement assessment, and free eculizumab circulating levels were systematically measured immediately before every injection given to 22 patients with hemolytic PNH while receiving eculizumab therapy. During the study, 6 patients received ≥1 red blood cell transfusion. Lack of detectable CH50 activity (defined by CH50 ≤ 10% of normal values) was found in 184 samples (51%) and was significantly associated with lower lactate dehydrogenase levels (P = .002). Low levels of circulating free eculizumab (<50 µg/mL) correlated with detectable CH50 activity (CH50 > 10%; P = .004), elevated bilirubin levels (P < .0001), and the need for transfusions (P = .034). This study suggests that both CH50 activity and circulating free eculizumab levels may help physicians to manage PNH patients receiving eculizumab.
阵发性睡眠性血红蛋白尿症 (PNH) 的特征是血管内溶血，用依库珠单抗（一种与人补体蛋白 5（C5）结合的人源化单克隆抗体）可有效控制。C5 的残留功能活性可通过 50%溶血补体（CH50）测定进行筛选，该测定对经典和末端补体途径的任何成分的减少、缺失和/或失活均敏感。关于治疗期间补体阻断的数据很少。2010 年至 2012 年，我们对 22 例接受依库珠单抗治疗的溶血性 PNH 患者，在每次接受治疗前，系统地测量了临床数据、溶血生物标志物、补体评估和游离依库珠单抗循环水平。在研究期间，6 例患者接受了≥1 次红细胞输注。在 184 个样本（51%）中发现缺乏可检测的 CH50 活性（定义为 CH50≤正常值的 10%），且与较低的乳酸脱氢酶水平显著相关（P=0.002）。循环游离依库珠单抗水平较低（<50μg/mL）与可检测的 CH50 活性（CH50>10%；P=0.004）、胆红素水平升高（P<0.0001）和需要输血（P=0.034）相关。这项研究表明，CH50 活性和循环游离依库珠单抗水平可能有助于医生管理接受依库珠单抗治疗的 PNH 患者。
