Merle N S, Boudhabhay I, Leon J, Fremeaux-Bacchi V, Roumenina L T
Centre de recherche des cordeliers, Inserm, Sorbonne université, USPC, Université Paris Descartes, Université Paris Diderot, 75006 Paris, France.
Centre de recherche des cordeliers, Inserm, Sorbonne université, USPC, Université Paris Descartes, Université Paris Diderot, 75006 Paris, France; Service d'immunologie biologique, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, Paris, France.
Transfus Clin Biol. 2019 May;26(2):116-124. doi: 10.1016/j.tracli.2019.02.008. Epub 2019 Feb 22.
Intravascular hemolysis is a hallmark of a large spectrum of diseases, including the sickle cell disease (SCD), and is characterized by liberation of red blood cell (RBC) degradation products in the circulation. Released Hb, heme, RBC fragments and microvesicles (MVs) exert pro-inflammatory, pro-oxidative and cytotoxic effects and contribute to vascular and tissue damage. The innate immune complement system not only contributes to the RBC lysis, but it is also itself activated by heme, RBC MVs and the hypoxia-altered endothelium, amplifying thus the cell and tissue damage. This review focuses on the implication of the complement system in hemolysis and hemolysis-mediated injuries in SCD and in cases of delayed hemolytic transfusion reactions (DHTR). We summarize the evidences for presence of biomarkers of complement activation in patients with SCD and the mechanisms of complement activation in DHTR. We discuss the role of antibodies-dependent activation of the classical complement pathway as well as the heme-dependent activation of the alternative pathway. Finally, we describe the available evidences for the efficacy of therapeutic blockade of complement in cases of DHTR. In conclusion, complement blockade is holding promises but future prospective studies are required to introduce Eculizumab or another upcoming complement therapeutic for DHTR and even in SCD.
血管内溶血是包括镰状细胞病（SCD）在内的多种疾病的一个标志，其特征是红细胞（RBC）降解产物在循环中释放。释放的血红蛋白（Hb）、血红素、红细胞碎片和微泡（MVs）具有促炎、促氧化和细胞毒性作用，并导致血管和组织损伤。天然免疫补体系统不仅有助于红细胞溶解，而且其自身也会被血红素、红细胞微泡和缺氧改变的内皮细胞激活，从而放大细胞和组织损伤。本综述重点关注补体系统在SCD以及迟发性溶血性输血反应（DHTR）中的溶血和溶血介导损伤中的作用。我们总结了SCD患者补体激活生物标志物存在的证据以及DHTR中补体激活的机制。我们讨论了抗体依赖性经典补体途径激活以及血红素依赖性替代途径激活的作用。最后，我们描述了在DHTR病例中补体治疗性阻断疗效的现有证据。总之，补体阻断有前景，但未来需要前瞻性研究来引入依库珠单抗或其他即将出现的用于DHTR甚至SCD的补体疗法。
