Yazdanbakhsh K
Complement Biology, New York Blood Center, NY 10021, USA.
Immunohematology. 2005;21(3):109-18.
The complement system plays a crucial role in fighting infections and is an important link between the innate and adaptive immune responses. However, inappropriate complement activation can cause tissue damage, and it underlies the pathology of many diseases. In the transfusion medicine setting, complement sensitization of RBCs can lead to both intravascular and extravascular destruction. Moreover, complement deficiencies are associated with autoimmune disorders, including autoimmune hemolytic anemia (AIHA). Complement receptor 1 (CR1) is a large single-pass glycoprotein that is expressed on a variety of cell types in blood, including RBCs and immune cells. Among its multiple functions is its ability to inhibit complement activation. Furthermore, gene knockout studies in mice implicate a role for CR1 (along with the alternatively spliced gene product CR2) in prevention of autoimmunity. This review discusses the possibility that the CR1 protein may be manipulated to prevent and treat AIHA. In addition, it will be shown in an in vivo mouse model of transfusion reaction that recombinant soluble forms of CR1 can reduce complement-mediated RBC destruction, thereby prolonging survival of transfused RBCs. It is proposed that CR1-based therapeutics have potential for effective and safe prophylactic short-term use and for treatment of hemolytic transfusion reactions.
补体系统在抗感染中发挥关键作用，是天然免疫反应和适应性免疫反应之间的重要纽带。然而，补体的不适当激活会导致组织损伤，并且是许多疾病病理过程的基础。在输血医学领域，红细胞的补体致敏可导致血管内和血管外破坏。此外，补体缺陷与自身免疫性疾病相关，包括自身免疫性溶血性贫血（AIHA）。补体受体1（CR1）是一种大型单次跨膜糖蛋白，在血液中的多种细胞类型上表达，包括红细胞和免疫细胞。其多种功能之一是具有抑制补体激活的能力。此外，小鼠基因敲除研究表明CR1（以及可变剪接基因产物CR2）在预防自身免疫中起作用。本综述讨论了操纵CR1蛋白以预防和治疗AIHA的可能性。此外，在输血反应的体内小鼠模型中将表明，重组可溶性CR1形式可减少补体介导的红细胞破坏，从而延长输注红细胞的存活时间。有人提出，基于CR1的疗法在有效且安全的短期预防以及溶血性输血反应的治疗方面具有潜力。
