Observational studyNature immunology2021
Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease.
Open access · bronzeAbstract readObservational Study
In one paragraph
Observational study in Nature immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- A therapeutic atlas of monogenic inflammatory bowel disease.Journal of Crohn's & colitis · 2026Pooled it
- The patient experience of CHAPLE disease: results from interviews conducted as part of a clinical trial for an ultra-rare condition.Orphanet journal of rare diseases · 2025Trial
- Evaluating the efficacy and safety of pozelimab in patients with CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy disease: an open-label phase 2 and 3 study.Lancet (London, England) · 2024Trial
- Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease.Nature immunology · 2022Trial
- C5 inhibition restores B cell homeostasis and humoral immunity in CHAPLE disease patients.Journal of human immunity · 2026Article
- The evolving landscape of complement therapeutics in rheumatology.Annals of the rheumatic diseases · 2026Review
- A Comprehensive Assessment of Health-Related Quality of Life in Hereditary Angioedema as a Patient-Centered Approach.International archives of allergy and immunology · 2026Article
- SARS-CoV-2 enhances complement-mediated endothelial injury via the suppression of membrane complement regulatory proteins.Emerging microbes & infections · 2025Article
- Population pharmacokinetic analyses of pozelimab in patients with CD55-deficient protein-losing enteropathy (CHAPLE disease).Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Cellular and molecular basis of proximal small intestine disorders.Nature reviews. Gastroenterology & hepatology · 2024Review
- Impact of High-Temperature Feeds on Gut Microbiota and MAFLD.Journal of microbiology and biotechnology · 2024Article
- Local complement activation and modulation in mucosal immunity.Mucosal immunology · 2024Review
- Factors affecting decisions of an HMO Drug Exemptions Committee on individual patient requests for coverage of non-formulary drugs.Israel journal of health policy research · 2024Article
- Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.Inflammatory bowel diseases · 2024Review
- Double-Edged Sword: Exploring the Mitochondria-Complement Bidirectional Connection in Cellular Response and Disease.Biology · 2024Review
- Precision medicine in monogenic inflammatory bowel disease: proposed mIBD REPORT standards.Nature reviews. Gastroenterology & hepatology · 2023Review
- Pozelimab: First Approval.Drugs · 2023Review
- CD55-deficiency in Jews of Bukharan descent is caused by the Cromer blood type Dr(a-) variant.Human genetics · 2023Article
- Special issue: the genetics of early onset inflammatory bowel disease (IBD) and diarrheal disorders.Human genetics · 2023Article
- Beyond IBD: the genetics of other early-onset diarrhoeal disorders.Human genetics · 2023Review
Corrections and comments
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Authors and funding
45 authors at 15 institutions in 3 countries.
Ahmet OzenDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey. ahmet.ozen@marmara.edu.tr.ORCID http://orcid.org/0000-0002-9065-1901
Nurhan KasapDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Ivan Vujkovic-CvijinMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8611-4900
Richard AppsTrans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD, USA.
Foo CheungTrans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD, USA.
Elif Karakoc-AydinerDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Bilge AkkelleDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Sinan SariDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, School of Medicine, Gazi University, Ankara, Turkey.
Engin TutarDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Figen OzcayDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baskent University Hospital, Ankara, Turkey.
Dilara Kocacik UygunDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Akdeniz University, Antalya, Turkey.
Ali IslekDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Ataturk University, Erzurum, Turkey.
Gamze AkgunIstanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey.
Merve SelcukDepartment of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Oya Balci SezerDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baskent University Hospital, Ankara, Turkey.
Yu ZhangHuman Immunological Diseases Section, Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA.
Gunsel KutlukDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Kanuni Sultan Süleyman Training and Research Hospital, Health Sciences University, Istanbul, Turkey.
Erdem TopalDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Inonu University, Malatya, Turkey.
Ersin SayarDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Alanya Alaaddin Keykubat University, Alanya, Turkey.
Cigdem CelikelDepartment of Pathology, School of Medicine, Marmara University, Istanbul, Turkey.
Roderick H J HouwenDepartment of Pediatric Gastroenterology, University Medical Center-Wilhelmina Children's Hospital, Utrecht, the Netherlands.
Aysen BingolDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Akdeniz University, Antalya, Turkey.
Ismail OgulurDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Sevgi Bilgic EltanIstanbul Jeffrey Modell Diagnostic Center for Primary Immunodeficiency Diseases, Istanbul, Turkey.
Andrew L SnowDepartment of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Camille LakeDepartment of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Giovanna FantoniTrans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD, USA.
Camille AlbaThe American Genome Center, Henry Jackson Foundation, Uniformed Services University of Health Sciences, Bethesda, MD, USA.
Brian SellersTrans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD, USA.
Samuel D ChauvinClinical Genomics Program, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-0232-751X
Clifton L DalgardDepartment of Anatomy, Physiology and Genetics, The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
Olivier HarariRegeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
Yan G NiRegeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
Ming-Dauh WangRegeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
Kishor Devalaraja-NarashimhaRegeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
Poorani SubramanianBioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-4371-7290
Rabia ErgelenDepartment of Radiology, School of Medicine, Marmara University, Istanbul, Turkey.
Reha ArtanDivision of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, School of Medicine, Akdeniz University, Antalya, Turkey.
Sukru Nail GunerDivision of Pediatric Allergy and Immunology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.
Buket DalgicDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, School of Medicine, Gazi University, Ankara, Turkey.
John TsangTrans-NIH Center for Human Immunology, Autoimmunity, and Inflammation, NIH, Bethesda, MD, USA.
Yasmine BelkaidMetaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9962-3571
Deniz ErtemDivision of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Safa BarisDivision of Allergy and Immunology, Department of Pediatrics, School of Medicine, Marmara University, Istanbul, Turkey.
Michael J LenardoClinical Genomics Program, NIAID, NIH, Bethesda, MD, USA. lenardo@nih.gov.ORCID http://orcid.org/0000-0003-1584-468X
Marmara University · TRNational Institutes of Health · USRegeneron (United States) · USAkdeniz University · TRUniformed Services University of the Health Sciences · USBaşkent University Hospital · TRGazi University · TRAlanya University · TRAtatürk University · TRInonu University · TRJackson Foundation · USNaval Research Laboratory Information Technology DivisionNecmettin Erbakan University · TRSağlık Bilimleri Üniversitesi · TRWilhelmina Children's Hospital · NL
Funding
Center for Human Immunology ZICAI001226 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2018 to 2025
$34.1MRole of the microbiota in immunityZIAAI001115 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2009 to 2025
$22.4MNIAID Microbiome ProgramZICAI001233 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOUTSOPOULOS, NIKI · 2018 to 2025
$18.9MMolecular Mechanisms Of The Autoimmune Lymphoproliferative Syndrome And Other Immunoregulatory DisordersZIAAI000769 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI SU, HELEN · 2009 to 2024
$16.7MIntegrative analysis and modeling of human immune responses and pathologiesZIAAI001152 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI TSANG, JOHN · 2011 to 2022
$14.1MRole of Tissue-Specific Factors in the Control of ImmunityZIAAI001132 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2011 to 2025
$6.4MRole of Vitamins in the Control of ImmunityZIAAI001133 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2010 to 2025
$6.1MChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2MMolecular Mechanisms Of The Autoimmune SyndromeZ01AI000769 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI LENARDO, MICHAEL · 1997 to 2008
$1.1MIntramural NIH HHS Z01 AI000769NIGMS NIH HHS R01 GM129325
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.
Indexed as
Antibodies, Monoclonal, HumanizedBiomarkersCD55 AntigensComplement ActivationComplement C5Complement Inactivating AgentsEnergy MetabolismGenetic Predisposition to DiseaseHumansHypoproteinemiaImmunity, InnateMutationPhenotypeProtein-Losing EnteropathiesTreatment OutcomeAntibodies, Monoclonal, HumanizedBiomarkersCD55 AntigensComplement C5Complement Inactivating Agentseculizumab
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