美国国立卫生研究院NIAID临床基因组计划Michael J. Lenardo和土耳其马尔马拉大学医学院Ahmet Ozen研究组合作取得最新进展。他们发现在补体过度活化、血管性血栓形成和蛋白质丢失性肠病（CHAPLE疾病）中具有C5抑制作用的广泛有效的代谢和免疫恢复。2021年1月4日出版的《自然-免疫学》杂志发表了这一成果。

他们报告了体内补体C5抑制剂依库丽单抗治疗CHAPLE疾病患者的数据。他们观察到胃肠道病理中止以及正常免疫力和新陈代谢的恢复。他们发现，患者可通过适体分析快速恢复免疫球蛋白浓度和其他血清蛋白的正常值，重新建立健康的肠道微生物组，中止免疫球蛋白替代和其他治疗并表现出追赶性生长。因此，他们表明依库丽单抗对C5的阻断有效地重新建立了对先天性免疫补体系统的调节，从而大大降低了人类CD55缺乏的病理生理表现。

据介绍，CHAPLE疾病是由补体调节蛋白CD55的遗传缺失引起的致死性疾病，导致补体和先天免疫过度活化，以及肠道中免疫球蛋白的浪费导致免疫缺陷。

附：英文原文

Title: Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease

Author: Ahmet Ozen, Nurhan Kasap, Ivan Vujkovic-Cvijin, Richard Apps, Foo Cheung, Elif Karakoc-Aydiner, Bilge Akkelle, Sinan Sari, Engin Tutar, Figen Ozcay, Dilara Kocacik Uygun, Ali Islek, Gamze Akgun, Merve Selcuk, Oya Balci Sezer, Yu Zhang, Gunsel Kutluk, Erdem Topal, Ersin Sayar, Cigdem Celikel, Roderick H. J. Houwen, Aysen Bingol, Ismail Ogulur, Sevgi Bilgic Eltan, Andrew L. Snow, Camille Lake, Giovanna Fantoni, Camille Alba, Brian Sellers, Samuel D. Chauvin, Clifton L. Dalgard, Olivier Harari, Yan G. Ni, Ming-Dauh Wang, Kishor Devalaraja-Narashimha, Poorani Subramanian, Rabia Ergelen, Reha Artan, Sukru Nail Guner, Buket Dalgic, John Tsang, Yasmine Belkaid, Deniz Ertem, Safa Baris, Michael J. Lenardo

Issue&Volume: 2021-01-04

Abstract: Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans. CHAPLE disease is a lethal syndrome caused by genetic loss of the complement regulatory protein CD55. Lenardo, Ozen and their colleagues report that blockade of C5 complement activation in a small cohort of pediatric patients with CHAPLE disease reduced gastrointestinal pathology and restored their immunity and growth.

DOI: 10.1038/s41590-020-00830-z

Source: https://www.nature.com/articles/s41590-020-00830-z