Mastellos Dimitrios C, Ricklin Daniel, Yancopoulou Despina, Risitano Antonio, Lambris John D
NCSR 'Demokritos' - INRASTES, Division of Biodiagnostic Sciences and Technologies, Aghia Paraskevi Attikis, Greece.
Expert Rev Hematol. 2014 Oct;7(5):583-98. doi: 10.1586/17474086.2014.953926. Epub 2014 Sep 2.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder associated with an acquired deficiency in glycophosphatidylinositol-anchor biosynthesis that renders erythrocytes susceptible to complement attack. Intravascular hemolysis via the membrane attack complex is a clinical hallmark of the disease, and C5 blockade is currently the only approved treatment for PNH. However, residual anemia is an emerging observation for many PNH patients receiving anti-C5 treatment. A range of complement-targeted therapeutic approaches, encompassing surface-directed inhibition of C3 convertases, blockade of membrane attack complex assembly or C3 interception using peptidic inhibitors, has yielded promising results and offers leverage for even more effective treatment of PNH. This article discusses recent advances in this rapidly evolving field, integrating critical perspectives from preclinical PNH models and diverse complement modulation strategies with genetic insights and therapy response profiles. It also evaluates the relative efficacy, limitations and benefits afforded by C3 or C5 inhibition in the context of PNH therapeutics.
阵发性夜间血红蛋白尿（PNH）是一种罕见的血液系统疾病，与糖磷脂酰肌醇锚生物合成的后天缺陷相关，该缺陷使红细胞易受补体攻击。通过膜攻击复合物进行的血管内溶血是该疾病的临床特征，目前C5阻断是PNH唯一获批的治疗方法。然而，对于许多接受抗C5治疗的PNH患者来说，残余贫血是一个新出现的现象。一系列针对补体的治疗方法，包括对C3转化酶的表面定向抑制、膜攻击复合物组装的阻断或使用肽类抑制剂进行C3拦截，都取得了有前景的结果，并为更有效地治疗PNH提供了手段。本文讨论了这个快速发展领域的最新进展，将临床前PNH模型和不同补体调节策略的关键观点与遗传学见解和治疗反应概况相结合。它还评估了在PNH治疗背景下C3或C5抑制所提供的相对疗效、局限性和益处。
