CHAPLE disease is a rare, inherited immune disorder that often appears in childhood and can be life-threatening. Its full name, CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and severe protein-losing enteropathy, reflects the condition’s complex nature. While fewer than 100 individuals worldwide are known to have it, its study is an important area of ongoing research.
Understanding CHAPLE Disease
CHAPLE disease is rooted in genetic mutations within the CD55 gene. This gene is responsible for producing the CD55 protein, also known as decay-accelerating factor (DAF), which acts as a regulator within the body’s complement system. The complement system is a part of the innate immune system, functioning as a defense against infections by helping to eliminate microbes.
The CD55 protein normally helps to control the complement cascade, specifically by regulating certain enzymes (C3- and C5-convertases) in both the classical and alternative pathways. In individuals with CHAPLE disease, the absence or malfunction of the CD55 protein leads to unchecked activation of the complement system. This hyperactivation results in the immune system mistakenly attacking the body’s own healthy cells.
The damaging effects of this overactive complement system are particularly pronounced in the gastrointestinal tract and blood vessels. The uncontrolled inflammation in the gut, especially in lymphatic vessels, leads to their abnormal dilation, a condition called intestinal lymphangiectasia. This allows lymph fluid, along with important proteins like albumin and immunoglobulins, to leak into the intestine, causing severe protein loss.
Signs and Symptoms
Individuals with CHAPLE disease experience a range of severe and varied symptoms, primarily affecting their digestive system and overall health. Abdominal pain, nausea, and vomiting are common, along with chronic diarrhea that can lead to significant weight loss and malabsorption of nutrients. This chronic malabsorption can cause deficiencies in various substances, including iron, calcium, magnesium, and certain vitamins.
The protein loss through the gut frequently results in hypoalbuminemia, or low albumin levels in the blood, which manifests as swelling, particularly in the limbs and face. Patients may also experience recurrent infections due to the loss of protective immune proteins. A concerning aspect of CHAPLE disease is the heightened risk of severe blood vessel blockages, known as thrombotic vascular occlusions, which can be life-threatening.
How CHAPLE Disease is Diagnosed
Diagnosing CHAPLE disease typically begins with clinical suspicion based on a patient’s symptoms, especially severe protein-losing enteropathy. Initial laboratory tests often reveal low levels of proteins in the blood, such as albumin. These findings suggest a problem with protein loss from the digestive system.
The definitive diagnosis relies on genetic testing to identify mutations in the CD55 gene. This genetic analysis confirms the underlying cause of the disease by showing a lack of functional CD55 protein. This precise genetic confirmation is important for distinguishing CHAPLE disease from other conditions that might present with similar symptoms.
Current Treatment Approaches
The primary treatment strategy for CHAPLE disease focuses on controlling the overactive complement system. Complement inhibitors are a specific class of medications designed to block this uncontrolled immune response. Veopoz (pozelimab-bbfg) is the first FDA-approved treatment for CHAPLE disease in patients one year of age and older.
Pozelimab-bbfg is a monoclonal antibody that targets complement protein C5, preventing its cleavage into C5a and C5b, which ultimately blocks the formation of the membrane attack complex (MAC). MAC is a structure that can damage and lyse healthy cells. By inhibiting C5, Veopoz helps to stop the self-inflicted damage caused by the overactive complement system, particularly in the gastrointestinal tract.
Another complement inhibitor, eculizumab, has also shown effectiveness in treating CHAPLE disease. Eculizumab is a humanized monoclonal antibody that also binds to the terminal complement component C5, preventing its activation. This therapy can alleviate gastrointestinal issues and help restore normal immune function and metabolism. In addition to these targeted therapies, supportive care, such as nutritional support, is often provided to manage symptoms like protein loss and ensure adequate nutrient intake.