Open AccessBroadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease
Author(s) -
Ahmet Özen,
Nurhan Kasap,
Ivan Vujkovic-Cvijin,
Richard Apps,
Foo Cheung,
Elif Karakoç-Aydıner,
Bilge Şahin Akkelle,
Sinan Sarı,
Engin Tutar,
Figen Özçay,
Dilara Kocacik Uygun,
Ali İşlek,
Gamze Akgun,
Merve Selcuk,
Oya Balcı Sezer,
Yu Zhang,
Günsel Kutluk,
Erdem Topal,
Ersin Sayar,
Çiğdem Ataizi Çelikel,
Roderick H. J. Houwen,
Ayşen Bingöl,
İsmail Öğülür,
Sevgi Bilgiç Eltan,
Andrew L. Snow,
Camille Lake,
Giovanna Fantoni,
Camille Alba,
Brian A. Sellers,
Samuel D. Chauvin,
Clifton L. Dalgard,
Olivier Harari,
Ni Yan,
Ming-Dauh Wang,
Kishor Devalaraja-Narashimha,
Poorani Subramanian,
Rabia Ergelen,
Reha Artan,
Şükrü Nail Güner,
Buket Dalgıç,
John S. Tsang,
Yasmine Belkaid,
Deniz Ertem,
Safa Barış,
Michael J. Lenardo
Publication year - 2021
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-020-00830-z
Subject(s) - eculizumab , enteropathy , immunology , complement system , innate immune system , biology , immune system , complement component 5 , immunity , antibody , common variable immunodeficiency , disease , medicine
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.