Broadly Effective Metabolic and Immune Recovery with C5 Inhibition in CHAPLE Disease

Overview

Journal Nat Immunol

Date 2021 Jan 5

PMID 33398182

Citations 18

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

SARS-CoV-2 enhances complement-mediated endothelial injury via the suppression of membrane complement regulatory proteins.

Wu J, Xu S, Li Z, Cong B, Yang Z, Yang Z Emerg Microbes Infect. 2025; 14(1):2467781.

PMID: 39945674 PMC: 11873982. DOI: 10.1080/22221751.2025.2467781.

The patient experience of CHAPLE disease: results from interviews conducted as part of a clinical trial for an ultra-rare condition.

Litcher-Kelly L, Ozen A, Ollis S, Feldman H, Yaworsky A, Medrano P Orphanet J Rare Dis. 2025; 20(1):68.

PMID: 39934837 PMC: 11817392. DOI: 10.1186/s13023-024-03436-y.

Population pharmacokinetic analyses of pozelimab in patients with CD55-deficient protein-losing enteropathy (CHAPLE disease).

Lin K, Mendell J, Davis J, Harnisch L J Pharmacokinet Pharmacodyn. 2024; 51(6):905-917.

PMID: 39349796 PMC: 11579122. DOI: 10.1007/s10928-024-09941-8.

Cellular and molecular basis of proximal small intestine disorders.

Bildstein T, Charbit-Henrion F, Azabdaftari A, Cerf-Bensussan N, Uhlig H Nat Rev Gastroenterol Hepatol. 2024; 21(10):687-709.

PMID: 39117867 DOI: 10.1038/s41575-024-00962-9.

Impact of High-Temperature Feeds on Gut Microbiota and MAFLD.

Xue L, Li K, Jia Y, Yao D, Guo X, Zhang S J Microbiol Biotechnol. 2024; 34(9):1789-1802.

PMID: 39113196 PMC: 11473614. DOI: 10.4014/jmb.2405.05023.

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