Article detail · 2017
CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis
- Year
- 2017
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue New England Journal of Medicine
- Catalog match (ISSN) New England Journal of Medicine
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
BACKGROUND: Studies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies. METHODS: We studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients' cells, which we confirmed by means of exogenous induction of expression of CD55. RESULTS: We identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients' T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation. CONCLUSIONS: 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. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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Citations
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205 citations
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23 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency 2018
- Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency 2018
- A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects 2019
- A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects 2019
- A Spectrum of Clinical Findings from ALPS to CVID: Several Novel LRBA Defects 2019
- Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease 2021
- Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease 2021
- Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease 2021
- Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease 2021
- Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease. 2021