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

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 CelikelRoderick 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)128-139
Number of pages12
JournalNature Immunology
Volume22
Issue number2
DOIs
StatePublished - Feb 2021
Externally publishedYes

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