We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
PURITAN MEDICAL

Download Mobile App




Events

09 Apr 2024 - 12 Apr 2024
15 Apr 2024 - 17 Apr 2024
23 Apr 2024 - 26 Apr 2024

Gene Mutation Causes Rare Immune Disorder

By LabMedica International staff writers
Posted on 12 Jul 2017
Print article
Image: This light microscope image shows the gut tissue of a child with CHAPLE disease. The large white areas in the bottom right corner are enlarged lymphatic vessels, which can contribute to intestinal distress (Photo courtesy of the US National Institute of Allergy and Infectious Diseases).
Image: This light microscope image shows the gut tissue of a child with CHAPLE disease. The large white areas in the bottom right corner are enlarged lymphatic vessels, which can contribute to intestinal distress (Photo courtesy of the US National Institute of Allergy and Infectious Diseases).
A genetic cause and potential treatment strategy for a rare immune disorder called CHAPLE disease has been discovered and children with the condition can experience severe gastrointestinal distress and deep vein blood clots.

Genetic studies have contributed to the understanding of gastrointestinal diseases, associating at least 64 genes with early-onset or very-early-onset inflammatory bowel disease. Deleterious gene variants affect the intestinal epithelial barrier, phagocytosis processes, immune regulation, and inflammation.

A large team of international scientists led by those at the US National Institute of Allergy and Infectious Diseases (Bethesda, MD, USA) enrolled 10 patients with CHAPLE disease that were based in Turkey and one who was based in the Netherlands, along with their healthy parents and siblings when available. The 11 patients were from eight families, all of whom were of Moroccan, Syrian, or Turkish ancestry. The ages of the patients ranged from three to 23 years as of February 2017. CHAPLE disease is a form of primary intestinal lymphangiectasia (PIL), also known as Waldmann’s disease.

Genomic DNA (gDNA) was obtained from probands and family members by isolation and purification from peripheral blood mononuclear cells (PBMCs) and submitted for Whole Exome Sequencing (WES) or targeting sequencing of the CD55 gene coupled with massively parallel sequencing by HiSeq Sequencing System. The scientists used a variety of techniques including flow cytometry, quantitative real-time polymerase reaction, Western blotting and T cell stimulation and cytokine secretion analysis.

The team found 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.

The team found that in CHAPLE disease, uninhibited complement resulting from a lack of CD55 protein damaged blood and lymph vessels along the lower digestive tract, leading to the loss of protective immune proteins and blood cells. In many patients, this process caused a range of symptoms, such as abdominal pain, bloody diarrhea, vomiting, problems absorbing nutrients, slow growth, swelling in the legs, recurrent lung infections, and blood clots.

The authors concluded that 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 the CD55 gene. The study was published on June 28, 2017, in the New England Journal of Medicine.

Related Links:
US National Institute of Allergy and Infectious Diseases

Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
One Step HbA1c Measuring System
GREENCARE A1c
POCT Fluorescent Immunoassay Analyzer
FIA Go
New
Gold Member
Magnetic Bead Separation Modules
MAG and HEATMAG

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The OvaCis Rapid Test discriminates benign from malignant epithelial ovarian cysts (Photo courtesy of INEX)

Intra-Operative POC Device Distinguishes Between Benign and Malignant Ovarian Cysts within 15 Minutes

Ovarian cysts represent a significant health issue for women globally, with up to 10% experiencing this condition at some point in their lives. These cysts form when fluid collects within a thin membrane... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.