Abstract：
The complement is a crucial factor of the innate immune system. However, its activation can lead to various diseases, so it needs to be controlled. In mammals, surface-bound complement regulatory proteins safeguard cells from uncontrolled complement-mediated lysis. One of the human complement regulators is CD55, also known as the decay-accelerating factor (DAF), a single-chain, type I cell surface protein anchored to glycosylphosphatidylinositol (GPI). The genetic loss of the complement regulatory protein CD55 leads to a fatal illness known as CHAPLE disease. The complement and innate immunity become hyperactive in this disease, causing angiopathic thrombosis and protein-losing enteropathy. Patients with CHAPLE disease experience abdominal pain, nausea, vomiting, diarrhea, loss of appetite, weight loss, impaired growth, and swelling. This genetic condition has no known cure, and managing its symptoms can be challenging. Pozelimab, a human monoclonal immunoglobulin IgG4 antibody, is a drug that targets the terminal complement protein C5. The drug has a high affinity for both wild-type and variant human C5. Pozelimab has received designations such as fast track, orphan drug, and rare pediatric disease, making it a significant medical breakthrough. It is currently the only available treatment for this disease. In this review, we have summarized the preclinical and clinical data on pozelimab.
摘要：
补体是先天免疫系统的关键因素。然而,它的激活会导致各种疾病，所以需要控制.在哺乳动物中,表面结合的补体调节蛋白保护细胞免受不受控制的补体介导的裂解。人类补体调节因子之一是CD55，也称为衰减加速因子（DAF），一个单链,I型细胞表面蛋白锚定于糖基磷脂酰肌醇(GPI)。补体调节蛋白CD55的遗传缺失导致称为CHAPLE疾病的致命疾病。补体和先天免疫在这种疾病中变得过度活跃，引起血管病性血栓形成和蛋白质丢失性肠病。CHAPLE疾病患者经历腹痛，恶心,呕吐,腹泻,食欲不振,减肥,增长受损，和肿胀。这种遗传病没有治愈方法，管理其症状可能具有挑战性。Pozelimab,人单克隆免疫球蛋白IgG4抗体，是一种靶向末端补体蛋白C5的药物。该药物对野生型和变体人C5均具有高亲和力。Pozelimab收到了诸如快速通道之类的名称，孤儿药,和罕见的儿科疾病，使其成为重大的医学突破。它是目前治疗这种疾病的唯一方法。在这次审查中,我们总结了pozelimab的临床前和临床数据。
