OBJECTIVES: Loss of the complement inhibitor CD55 leads to a syndrome of early-onset protein-losing enteropathy (PLE), associated with intestinal lymphangiectasia and susceptibility to large-vein thrombosis. The in vitro and short-term treatment benefits of eculizumab (C5-inhibitor) therapy for CD55-deficiency have been previously demonstrated. Here we present the 18-months treatment outcomes for 3 CD55-deficiency patients with sustained therapeutic response. METHODS: Three CD55-deficiency patients received off-label eculizumab treatment. Clinical and laboratory treatment outcomes included frequency and consistency of bowl movements, weight, patient/parent reports of overall well-being, and serum albumin and total protein levels. Membrane attack complex deposition on leukocytes was tested by flow cytometry, before and during eculizumab treatment. RESULTS: Marked clinical improvement was noted in all 3 patients with resolution of PLE manifestations, that is, diarrhea, edema, malabsorption, overall well-being, growth, and quality of life. In correlation with the clinical observations, we observed progress in all laboratory outcome parameters, including increase in albumin and total protein levels, and up to 80% reduction in membrane attack complex deposition on leukocytes (P < 0.001). The progress persisted over 18 months of treatment without any severe adverse events. CONCLUSIONS: CD55-deficiency patients present with early-onset diarrhea, edema, severe hypoalbuminemia, abdominal pain, and malnutrition. Targeted therapy with the terminal complement inhibitor eculizumab has positive clinical and laboratory outcomes in PLE related to CD55 loss-of-function mutations, previously a life-threatening condition. Our results demonstrate the potential of genetic diagnosis to guide tailored treatment, and underscore the significant role of the complement system in the intestine.
OBJECTIVES: Loss of the complement inhibitor CD55 leads to a syndrome of early-onset protein-losing enteropathy (PLE), associated with intestinal lymphangiectasia and susceptibility to large-vein thrombosis. The in vitro and short-term treatment benefits of eculizumab (C5-inhibitor) therapy for CD55-deficiency have been previously demonstrated. Here we present the 18-months treatment outcomes for 3 CD55-deficiencypatients with sustained therapeutic response. METHODS: Three CD55-deficiencypatients received off-label eculizumab treatment. Clinical and laboratory treatment outcomes included frequency and consistency of bowl movements, weight, patient/parent reports of overall well-being, and serum albumin and total protein levels. Membrane attack complex deposition on leukocytes was tested by flow cytometry, before and during eculizumab treatment. RESULTS: Marked clinical improvement was noted in all 3 patients with resolution of PLE manifestations, that is, diarrhea, edema, malabsorption, overall well-being, growth, and quality of life. In correlation with the clinical observations, we observed progress in all laboratory outcome parameters, including increase in albumin and total protein levels, and up to 80% reduction in membrane attack complex deposition on leukocytes (P < 0.001). The progress persisted over 18 months of treatment without any severe adverse events. CONCLUSIONS:CD55-deficiencypatients present with early-onset diarrhea, edema, severe hypoalbuminemia, abdominal pain, and malnutrition. Targeted therapy with the terminal complement inhibitor eculizumab has positive clinical and laboratory outcomes in PLE related to CD55 loss-of-function mutations, previously a life-threatening condition. Our results demonstrate the potential of genetic diagnosis to guide tailored treatment, and underscore the significant role of the complement system in the intestine.
Authors: Alina Kurolap; Florian Kreuder; Claudia Gonzaga-Jauregui; Morasha Plesser Duvdevani; Tamar Harel; Luna Tammer; Baozhong Xin; Somayeh Bakhtiari; James Rice; Clare L van Eyk; Jozef Gecz; Jean K Mah; Derek Atkinson; Heidi Cope; Jennifer A Sullivan; Alon M Douek; Daniel Colquhoun; Jason Henry; Donald Wlodkowic; Yesim Parman; Ayşe Candayan; Elif Kocasoy-Orhan; Anat Ilivitzki; Shiri Soudry; Rina Leibu; Fabian Glaser; Valerie Sency; Gil Ast; Vandana Shashi; Michael C Fahey; Esra Battaloğlu; Albena Jordanova; Vardiella Meiner; A Micheil Innes; Heng Wang; Orly Elpeleg; Michael C Kruer; Jan Kaslin; Hagit Baris Feldman Journal: Am J Hum Genet Date: 2022-02-01 Impact factor: 11.043
Authors: Jorik M van Rijn; Lael Werner; Yusuf Aydemir; Joey M A Spronck; Ben Pode-Shakked; Marliek van Hoesel; Elee Shimshoni; Sylvie Polak-Charcon; Liron Talmi; Makbule Eren; Batia Weiss; Roderick H J Houwen; Iris Barshack; Raz Somech; Edward E S Nieuwenhuis; Irit Sagi; Annick Raas-Rothschild; Sabine Middendorp; Dror S Shouval Journal: Int J Mol Sci Date: 2020-11-02 Impact factor: 5.923