RARE DISEASES

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New Treatment for CHAPLE Disease, a Rare Immune Disorder

 

CHAPLE disease is a form of primary intestinal lymphangiectasia (PIL), or Waldmann’s disease, first described in 1961 by Thomas A. Waldmann, M.D., an NIH Distinguished Investigator at the National Cancer Institute, at NIH.

 

According to an article published online in the New England Journal of Medicine (29 June 2017), a genetic cause and potential treatment strategy has been identified for a rare immune disorder called CHAPLE disease. Children with the condition can experience severe gastrointestinal distress and deep vein blood clots. No effective treatments are available to ameliorate or prevent these life-threatening symptoms. The study describes a newly understood mechanism for CHAPLE disease, also known as CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy.

 

For the study, genes from 11 children with CHAPLE disease and their families were analyzed. Results showed that each child had two copies of a defective CD55 gene that prevented them from producing a cell surface protein of the same name. The CD55 protein helps regulate the immune system by blocking the activity of complement, a group of immune system proteins that can fight infections by punching holes in the cell membranes of bacteria and other infectious agents. However, complement also can damage the body’s tissues. The study authors 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.

 

After discovering that complement hyperactivity was driving these severe symptoms, the authors tested drugs already approved by the U.S. FDA for the treatment of other diseases to see if they block this process in samples of patient immune cells. The authors found that complement production decreased when cells were exposed to eculizumab, a therapeutic antibody approved to treat another rare condition called paroxysmal nocturnal hemoglobinuria. The authors plan to study eculizumab in people with CHAPLE disease with the hope that the therapeutic could become the first effective treatment for the disorder.

 

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