Background: In patients with celiac disease, enterocytes (the cells that line the small intestine that are responsible for nutrient absorption and barrier functions) undergo apoptosis, or cell death, as a result of persistent inflammation. This results in villous atrophy of the small intestine.

A recent study published in Alimentary Pharmacology and Therapeutics demonstrated that a new, non-invasive test for celiac disease may be possible in the future.

Currently, the standard of care for celiac disease testing typically begins with an IgA-tTG blood test, although this assesses the immune response to gluten and not specifically intestinal damage or repair. Biopsies of the small intestine are required in order to determine if villous atrophy is present. Damage is scored using the Marsh scale, which categorizes disease stage based on the amount of destruction. While this method is accurate, biopsies are invasive and require a visit to a GI specialist who can perform an endoscopy.

In this paper, the authors explored the potential use of levels of intestinal fatty acid-binding protein (I-FABP) in the serum as a marker for intestinal damage. I-FABP is a protein that exists in the cytosol of mature enterocytes. When enterocytes undergo apoptosis, I-FABP is released into the blood stream and can be detected in serum (the liquid portion of blood). Testing for I-FABP levels would therefore involve a simple blood test, making it a non-invasive tool for evaluating intestinal damage.

Serum I-FABP levels were assessed for 96 patients with celiac disease and compared to 141 healthy control patients. Researchers determined that I-FABP levels were higher in patients with celiac disease, and I-FABP levels corresponded with intestinal damage as indicated by Marsh grade. By using a cutoff value of 382pg I-FABP per mL serum, this I-FABP test had an 80% sensitivity and 87.2% specificity for correctly identifying celiac disease patients. Additionally, they determined that levels were highest amongst patients prior to celiac disease diagnosis, and that levels of I-FABP declined upon adherence to a gluten-free diet. Celiac disease patients who had been gluten-free for 6 months had significantly lower levels of I-FABP than prior to diagnosis and that number continued to decline after one year of following a gluten-free diet. Importantly, at around 1-2 years post-diagnosis, the I-FABP levels plateau, and no additional repair is noted. Despite a Marsh score of 0-1, the I-FABP levels still remain higher in celiac disease patients on a gluten-free diet than in celiac-negative patients, which may indicate a persistent low level of intestinal of damage.

“This non-invasive test would not only be useful at time of diagnosis, but might potentially also be used as a marker of intestinal damage and recovery after initiation of a gluten-free diet. Serum I-FABP can potentially contribute to diminish the need for invasive duodenal biopsies both at time of diagnosis and during follow-up of the disease,” explained researcher Marlou Adriaanse, MD, PhD candidate Paediatric Gastroenterology at Maastricht University Medical Centre.

NFCA’s Take Home Message

This study demonstrates that a new, non-invasive blood test for intestinal damage in celiac disease patients may be possible. Although future validation will be required before it can be implemented in the clinic, this test could eliminate the requirement for biopsies in the diagnosis of celiac disease. This could drastically improve the diagnosis of celiac disease, particularly in rural or indigent areas where biopsies are not always possible and are often costly.

Visit Alimentary Pharmacology and Therapeutics for access to the full study.