Researchers just discovered a blood biomarker that predicts complicated Crohn’s disease uo to seven years before diagnosis.
Crohn’s disease is a chronic inflammatory condition of the intestine, for which simple and effective biomarkers prior to diagnosis are lacking. A blood test could provide a quick, cost-effective and non-invasive way to assess risk for complicated Crohn’s, which may enable preventive strategies before subclinical inflammation leads to chronic symptoms.
“Our team identified a serological biomarker for Crohn’s disease that also participates in its pathogenesis and occurs years before the disease shows its full clinical spectrum,” said Arthur Mortha, an assistant professor of immunology in U of T’s Temerty Faculty of Medicine. The findings were published in the journal Gastroenterology.
“The current arsenal of therapeutics that causes relieving remission in Crohn’s patients is good but suffers limitations. A biomarker or predictive indicators to guide interventions are a clinical need,” said Mortha. “In addition, our characterization of this biomarker suggests it is a suitable therapeutic target for intervention and maybe even prevention.”
The biomarker for complicated Crohn’s disease is an antibody produced by antibody-secreting cells in the gut. These antibodies prevent communication among intestinal immune cells by binding and blocking the function of a protein called a cytokine. This cytokine sustains immune balance in the intestine by promoting protective and anti-microbial immunity.
Mortha and his colleagues showed that in a large subset of Crohn’s patients, these antibodies neutralized the protective effects of the cytokine and disrupted intestinal homeostasis. Those changes were detectable in the blood of patients years before diagnosis and led to a weakening of the immune system that over time resulted in damage to the lower part of the small intestine – a condition known as complicated ileal Crohn’s disease.
The researchers used blood samples from the U.S. Department of Defense Serum Repository to identify and characterize the biomarker. They studied samples collected annually over a decade from 220 military personnel who developed Crohn’s and compared them to patients with ulcerative colitis and hundreds of healthy controls. The biomarker strongly predicted risk for complicated ileal Crohn’s, although not all patients with the antibody showed the exact same form and severity of the disease, which Mortha said highlights the multi-factorial nature of the condition. The biomarker was present in about a quarter of patients who developed Crohn’s.
Importantly, the team also found they could preserve the protective effects of the cytokine by manipulating its biochemical features. Engineered versions of the cytokine with improved biochemical features can be made practically invisible to the antibodies, Mortha said.
“Our system allows us to see how the antibodies in each patient specifically neutralize the cytokine. We are now engineering cytokines that can escape neutralization by these antibodies within individual patients,” Mortha said. This approach could enable highly personalized therapies that reverse the paralyzing effects of the antibodies and restore immune balance in the intestine.
“Maintaining a strong gut immune system is essential to control the commensal microbes living in our intestine. It’s mind-blowing that our mucosal immune system is capable of sustaining a defense against the enormous numbers of microbes in the gut, and that we’re not in complete agony,” Mortha said. “The past decade has taught us a lot about the modes of communication used by our gut immune cells to establish a healthy balance at this interface. It is now time to bring what we have learned to use.”
This article is based on a press release by the University of Toronto. You can find the original publication here and by following the link in our text.
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