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.
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.
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.
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.
*The Genetics Institute, Rambam Health Care Campus
†The Ruth and Bruce Rappaport Faculty of Medicine, Technion—Israel Institute of Technology
‡Pediatric Gastroenterology Unit and Pediatrics B, Rambam Health Care Campus, Haifa
§Rheumatology Research Center, Hadassah Medical Center and the Hebrew University, Jerusalem
||Department of Pediatric Surgery
¶Institute of Pathology, Rambam Health Care Campus, Haifa, Israel.
Address correspondence and reprint requests to Hagit Baris Feldman, MD, The Genetics Institute, Rambam Health Care Campus, Haifa, Israel (e-mail: firstname.lastname@example.org).
Received 28 August, 2018
Accepted 20 October, 2018
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).
This study was partially supported by the Technion EVPR Fund—Mallat Family Research Fund (to H.B.F.), and partially by the Legacy Heritage Bio-Medical Program of the Israel Science Foundation (ISF) (grant no. 1070/15 to D.M.).
A.K. and O.E.A. contributed equally to this work.
Eculizumab was provided by Alexion Pharmaceuticals, Inc, and the unique treatment regimen was constructed for our patients in consultation with the Alexion medical team. Alexion had no additional roles in study design, patient monitoring and follow-up, data analysis, or the preparation of the manuscript. The authors A.K., O.E.A., and H.N.B. have a pending patent with Alexion Pharmaceuticals, Inc, which does not include royalties. The remaining authors report no conflicts of interest.