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

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dc.contributor.authorÖZEN, AHMET OĞUZHAN
dc.contributor.authorsOzen, Ahmet; Kasap, Nurhan; Vujkovic-Cvijin, Ivan; Apps, Richard; Cheung, Foo; Karakoc-Aydiner, Elif; Akkelle, Bilge; Sari, Sinan; Tutar, Engin; Ozcay, Figen; Uygun, Dilara Kocacik; Islek, Ali; Akgun, Gamze; Selcuk, Merve; Sezer, Oya Balci; Zhang, Yu; Kutluk, Gunsel; Topal, Erdem; Sayar, Ersin; Celikel, Cigdem; Houwen, Roderick H. J.; Bingol, Aysen; Ogulur, Ismail; Eltan, Sevgi Bilgic; Snow, Andrew L.; Lake, Camille; Fantoni, Giovanna; Alba, Camille; Sellers, Brian; Chauvin, Samuel D.; Dalgard, Clifton L.; Harari, Olivier; Ni, Yan G.; Wang, Ming-Dauh; Devalaraja-Narashimha, Kishor; Subramanian, Poorani; Ergelen, Rabia; Artan, Reha; Guner, Sukru Nail; Dalgic, Buket; Tsang, John; Belkaid, Yasmine; Ertem, Deniz; Baris, Safa; Lenardo, Michael J.
dc.date.accessioned2022-03-14T09:59:43Z
dc.date.available2022-03-14T09:59:43Z
dc.date.issued2021-02
dc.description.abstractCHAPLE 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. 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.
dc.identifier.doi10.1038/s41590-020-00830-z
dc.identifier.eissn1529-2916
dc.identifier.issn1529-2908
dc.identifier.pubmed33398182
dc.identifier.urihttps://hdl.handle.net/11424/243846
dc.identifier.wosWOS:000604865800004
dc.language.isoeng
dc.publisherNATURE RESEARCH
dc.relation.ispartofNATURE IMMUNOLOGY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectDECAY-ACCELERATING FACTOR
dc.subjectPROTEIN-LOSING ENTEROPATHY
dc.subjectHEMOLYTIC-UREMIC SYNDROME
dc.subjectLUPUS-ERYTHEMATOSUS SLE
dc.subjectENDOTHELIAL-CELLS
dc.subjectCD55 DEFICIENCY
dc.subjectSINGLE-CELL
dc.subjectCOPY-NUMBER
dc.subjectCOMPLEMENT
dc.subjectECULIZUMAB
dc.titleBroadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease
dc.typearticle
dspace.entity.typePublication
local.avesis.ide41448bf-fc17-47f4-930f-4aabb49574d5
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages24
oaire.citation.endPageU24
oaire.citation.issue2
oaire.citation.startPage128
oaire.citation.titleNATURE IMMUNOLOGY
oaire.citation.volume22
relation.isAuthorOfPublication3e9c297b-e636-4836-8f61-dc9c8b7c29cf
relation.isAuthorOfPublication.latestForDiscovery3e9c297b-e636-4836-8f61-dc9c8b7c29cf

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