Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease
Göster/ Aç
Tarih
2021Yazar
Ozen, Ahmet
Kasap, Nurhan
Vujkovic-Cvijin, Ivan
Apps, Richard
Cheung, Foo
Karakoc-Aydiner, Elif
Akkelle, Bilge
Sari, Sinan
Tutar, Engin
Uygun, Dilara Kocacik
Islek, Ali
Akgun, Gamze
Selcuk, Merve
Sezer, Oya Balci
Ozcay, Figen
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.
Üst veri
Tüm öğe kaydını gösterÖzet
CHAPLE 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.