Blood changes found that predict onset of Crohn’s disease

An international team led by researchers from the Institute of Research and Innovation in Health at the University of Porto (i3S) has discovered a change in the blood that predicts the onset of Crohn’s disease.

The institute said in a statement Tuesday that “a unique antibody glycosylation signature has been discovered that can be detected in the blood many years before symptoms develop and diagnosis is made” of Crohn’s disease.

The study, led by Salome Pinho of i3S, was published in the scientific journal Nature Immunology.

Crohn’s disease is a chronic inflammatory bowel disease that causes inflammation of the digestive tract. The most common symptoms are diarrhea, abdominal pain, fatigue, and weight loss. The disease can affect all age groups, but is predominantly diagnosed in adolescents and young adults.

The researchers began by studying the intestinal inflammation that is common in patients with Crohn’s disease, focusing on characterizing the composition of glycans (complex sugars) that modify antibodies in the circulation.

To this end, thousands of sera from individual (military) blood samples were analyzed in the preclinical phase six years before the onset of the disease, a collaboration between Mount Sinai Hospital (New York) and the US Department of Defense.

Samples were collected at different times: closer to diagnosis, four and six years before diagnosis.

The researchers also analyzed blood samples from patients with established disease, as well as first-degree relatives of patients and healthy individuals, in collaboration with the gastroenterology services of the Centro Hospitalar Universitário Santo Antonio (Porto), Hospital Beatriz Angelo and Hospital da Luz (Lisbon).

In collaboration with researchers from Croatia, the glycosylation profile of circulating antibodies was characterized. The team found a “unique change” in the glycan composition of circulating antibodies and confirmed that this change was detectable six years before diagnosis and remained constant throughout the treatment period, prior to the onset of symptoms.

“This groundbreaking discovery opens the door to the identification of a non-invasive biomarker capable of predicting the diagnosis of Crohn’s disease and thus stratifying the risk of developing the disease,” i3S emphasizes.

The researchers also found that ASCA antibodies (found in 40-60% of patients) “have a glycoform that is pathogenic and begins to induce an inflammatory response many years before the disease is diagnosed,” according to a statement cited by researcher Salome Pinho.

Also in the statement, Joana Gaifem, one of the study’s first authors, emphasized that “a potential cause or one of the causes of this disease has been identified, as well as a potential target for future approaches to prevent Crohn’s disease.”

As part of the European GlycanTrigger project, led by Salomé Pinho, and based on their findings, researchers will next year conduct clinical trials on patients with Crohn’s disease who have had part of their intestine surgically removed.

The goal is to “modulate glycosylation” and try to understand its impact on the intestinal immune system and the gut microbiome, explains Joana Torres, a gastroenterologist at the Hospital da Luz, where recruitment of patients begins early next year.