Eculizumab Is Safe and Effective as a Long-term Treatment for Protein-losing Enteropathy Due to CD55 Deficiency

  title={Eculizumab Is Safe and Effective as a Long-term Treatment for Protein-losing Enteropathy Due to CD55 Deficiency},
  author={Alina Kurolap and Orly Eshach Adiv and Tova Hershkovitz and Adi Tabib and Netanel Karbian and Tamar Paperna and Adi Mory and Arcadi Vachyan and Nadav Slijper and Ran Steinberg and Yaniv Zohar and Dror Mevorach and Hagit Baris Feldman},
  journal={Journal of Pediatric Gastroenterology and Nutrition},
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… 
Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease
It is shown that blockade of C5 by eculizumab effectively re-establishes the regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.
CD55-deficiency in Jews of Bukharan descent is caused by the Cromer blood type Dr(a−) variant
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Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy
Despite resistance to anthrax-toxin, epithelial cell function, and specifically monolayer formation, is intact in patients with HFS, Nevertheless, loss of ANTXR2-mediated signaling leads to collagen VI accumulation in the duodenum and abnormal extracellular matrix composition, which likely plays a role in development of PLE.
Protein-Losing Enteropathy
New insights into the immune functions of complement
Fundamental mechanisms and novel concepts at the interface of complement biology and immunity are considered and how these affect the maintenance of homeostasis and the development of human pathology are discussed.
DDA-SKF: Predicting Drug–Disease Associations Using Similarity Kernel Fusion
A new computational model, DDA-SKF (drug–disease associations prediction using similarity kernels fusion), which can predict novel drug indications by utilizing similarity kernel fusion (SKF) and Laplacian regularized least squares (LapRLS) algorithms.


CD55 Deficiency, Early‐Onset Protein‐Losing Enteropathy, and Thrombosis
CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein‐losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss‐of‐function mutations in CD55.
Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria.
The beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied and were independent of baseline levels of hemolysis and degree of thrombocytopenia.
Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.
Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome and was also associated with improvement in health-related quality of life.
The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria.
Eculizumab is an effective therapy for PNH and Clinically significant improvements were found in the quality of life, as measured by scores on the Functional Assessment of Chronic Illness Therapy-Fatigue instrument and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire.
Protein-Losing Enteropathy: Case Illustrations and Clinical Review
Cases illustrating a variety of clinical presentations and etiologies of PLE are presented, and its diagnostic approach and treatment are reviewed.
Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation.
The rationale for the clinically observed phenomenon of residual terminal pathway activity under eculizumab treatment is delivered with important implications for anti-C5 therapy in general.
Primary intestinal lymphangiectasia (Waldmann's disease)
A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management, and the absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss.
Loss of CD55 in Eculizumab-Responsive Protein-Losing Enteropathy.
Three patients with protein-losing enteropathy and a genetic variant predicted to result in loss of function of CD55 had a response to eculizumab.