Abstract：
Complement factor I (FI) is the nexus for classical, lectin and alternative pathway complement regulation. FI is an 88 kDa plasma protein that circulates in an inactive configuration until it forms a trimolecular complex with its cofactor and substrate whereupon a structural reorganization allows the catalytic triad to cleave its substrates, C3b and C4b. In keeping with its role as the master complement regulatory enzyme, deficiency has been linked to immunopathology. In the setting of complete FI deficiency, a consumptive C3 deficiency results in recurrent infections with encapsulated microorganisms. Aseptic cerebral inflammation and vasculitic presentations are also less commonly observed. Heterozygous mutations in the factor I gene (CFI) have been demonstrated to be enriched in atypical haemolytic uraemic syndrome, albeit with a very low penetrance. Haploinsufficiency of CFI has also been associated with decreased retinal thickness and is a strong risk factor for the development of age-related macular degeneration. Supplementation of FI using plasma purified or recombinant protein has long been postulated, however, technical difficulties prevented progression into clinical trials. It is only using gene therapy that CFI supplementation has reached the clinic with GT005 in phase I/II clinical trials for geographic atrophy.
摘要：
补充因子I(FI)是经典，凝集素和替代途径补体调节。FI是一种88kDa血浆蛋白，以非活性构型循环，直到与其辅因子和底物形成三分子复合物，因此结构重组允许催化三联体裂解其底物，C3b和C4b。为了保持其作为主要补体调节酶的作用，缺乏与免疫病理学有关。在完全FI缺乏的情况下，消耗性C3缺乏导致包囊微生物的反复感染。无菌脑炎症和血管表现也较不常见。已证明因子I基因（CFI）的杂合突变在非典型溶血性尿毒症综合征中富集，尽管外显率很低.CFI的单倍功能不全也与视网膜厚度减少有关,并且是年龄相关性黄斑变性发展的强危险因素。使用血浆纯化或重组蛋白补充FI早已被假定，然而,技术困难阻碍了进入临床试验的进展。仅使用基因疗法，在地理萎缩的I/II期临床试验中，CFI补充已与GT005一起进入临床。
