The National Renal Complement Therapeutics Centre, aHUS Service, Building 26, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK.
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Semin Immunopathol. 2018 Jan;40(1):49-64. doi: 10.1007/s00281-017-0663-8. Epub 2018 Jan 11.
Atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and paroxysmal nocturnal hemoglobinuria (PNH) are prototypical disorders of complement dysregulation. Although complement overactivation is common to all, cell surface alternative pathway dysregulation (aHUS), fluid phase alternative pathway dysregulation (C3G), or terminal pathway dysregulation (PNH) predominates resulting in the very different phenotypes seen in these diseases. The mechanism underlying the dysregulation also varies with predominant acquired autoimmune (C3G), somatic mutations (PNH), or inherited germline mutations (aHUS) predisposing to disease. Eculizumab has revolutionized the treatment of PNH and aHUS although has been less successful in C3G. With the next generation of complement therapeutic in late stage development, these archetypal complement diseases will provide the initial targets.
非典型溶血性尿毒症综合征 (aHUS)、C3 肾小球病 (C3G) 和阵发性夜间血红蛋白尿症 (PNH) 是补体失调的典型疾病。尽管所有这些疾病都存在补体过度激活，但细胞表面替代途径失调 (aHUS)、液相反 应途径失调 (C3G) 或末端途径失调 (PNH) 占主导地位，导致这些疾病出现非常不同的表型。失调的机制也因主要获得性自身免疫性疾病 (C3G)、体细胞突变 (PNH) 或遗传种系突变 (aHUS) 而有所不同，这些疾病易导致疾病发生。依库珠单抗彻底改变了 PNH 和 aHUS 的治疗方法，尽管在 C3G 方面的疗效较差。随着下一代补体治疗药物进入后期开发阶段，这些典型的补体疾病将成为最初的治疗靶点。
