Blood biomarkers help track gut pathology in celiac disease

Celiac disease is an autoimmune condition in which the immune system reacts adversely to gluten. Eating gluten causes inflammation in the gut, which can damage the intestine and impair its ability to absorb nutrients.

The condition is treated by avoiding gluten entirely. Although many people with celiac disease adhere carefully to a gluten-free diet, current blood tests do not always show clearly whether inflammation or intestinal damage persists.

Many people with celiac disease are very diligent in following the diet, but they still live with uncertainty because the blood tests do not always give clear answers about how the disease is progressing."

Jostein Holen Ibsen, a PhD fellow and physician, Norwegian Celiac Disease Research Center, University of Oslo and the Clinical and Translational Celiac Disease Center, Oslo University Hospital

In a new study, Ibsen and colleagues investigated whether proteins in the blood could serve as biomarkers of disease activity. Biomarkers are measurable substances in the body that may indicate health or disease.

The researchers analyzed 264 blood and tissue samples from people with celiac disease, collected before treatment and after one year on a gluten-free diet. They also examined samples from people without celiac disease. The samples were collected at Rikshospitalet between 2018 and 2024, and all participants had consented to their use in research.

Using proteomics, a method that allows large numbers of proteins to be analyzed simultaneously, the team identified 24 proteins associated with celiac disease. Nine of these were particularly linked to the extent of intestinal damage and may indicate how far the disease has progressed.

"For many of the proteins, we found a clear difference between people with untreated celiac disease and healthy individuals," Ibsen says.

People with untreated celiac disease had the highest levels of inflammatory proteins, while healthy individuals had the lowest. The researchers also found clear differences between protein levels before and after treatment, suggesting that proteins in the blood may provide detailed information about inflammation and healing in the gut.

However, people with celiac disease who followed a gluten-free diet still had slightly higher levels of some proteins than healthy individuals.

"The findings therefore suggest that patients have some inflammation in the gut even when they follow the diet," Ibsen says.

Limits of current monitoring

Celiac disease is commonly diagnosed through a blood test and a gastroscopy, during which tissue samples are taken from the small intestine. The current blood test measures antibodies known as anti-tTG IgA, as well as total IgA levels.

After diagnosis, patients are generally monitored by their GP, often using the same blood test. However, Ibsen says the test is less informative once a patient has started a gluten-free diet.

"The problem with this blood test is that it simply does not work as well once patients have started treatment with a gluten-free diet," he says. "We have research showing that it can be somewhat misleading about what is actually happening in the gut."

The researchers hope that tests based on the newly identified biomarkers could eventually complement existing methods of monitoring celiac disease.

"Tests based on new biomarkers should not replace the tests we use today. However, they could help to provide a more accurate picture of how the disease is developing and offer more reassuring follow-up," Ibsen says.

Professor Knut E. A. Lundin says the findings are promising.

"There is potential for tests based on these new biomarkers to be used alongside serology, which is the test used today and which does not distinguish clearly enough between ongoing intestinal damage and healing," Lundin says.

Further studies involving more patients are needed before the approach can be used in clinical practice. Researchers must also select the proteins with the greatest potential for further investigation.

Ibsen emphasizes that the study depended on contributions from patients and healthy control participants.

"It is so valuable and important that patients donate samples to us. Patient contributions to research are crucial. Without them, we would not have been able to conduct this research," he says.