Researchers at Mount Sinai have identified new protein biomarkers of Crohn’s disease, and environmental factors that may increase a person’s risk of developing inflammatory bowel disease (IBD).
Together, these findings may help to develop new and more effective strategies for IBD prevention.
“Early identification of individuals at high risk for disease development could allow for close monitoring and interventions to delay, attenuate, or even halt disease initiation,” Jean-Frederic Colombel, MD, professor of gastroenterology at the Icahn School of Medicine at Mount Sinai, said in a press release. “This is highly relevant as we seek to predict and prevent IBD, which continues to sharply increase in numbers across the globe.”
Colombel is also co-director of Mount Sinai’s Susan and Leonard Feinstein Inflammatory Bowel Disease Clinical Center.
The findings were reported in four different studies, all published simultaneously in Gastroenterology, a journal of the American Gastroenterological Association.
In one of the studies, titled “Serum Biomarkers Identify Patients Who Will Develop Inflammatory Bowel Diseases Up to 5 y Before Diagnosis,” investigators reported the discovery of a panel of 51 protein biomarkers that can predict, with an accuracy of 76%, the development of Crohn’s disease five years prior to its definitive diagnosis.
The study was based on serum samples from military personnel, collected from 1998 to 2013, as part of the U.S. Defense Medical Surveillance System. In total, the investigators analyzed samples from 200 patients with Crohn’s, 199 with ulcerative colitis, and 200 healthy individuals (controls). All patient samples were collected before a definitive diagnosis.
“The study suggests that biological processes are activated many years before Crohn’s, opening the possibility of developing targeted strategies that could work to prevent or delay disease onset,” said Joana Torres, MD, PhD, lead author of the study and adjunct assistant professor of gastroenterology at the Icahn School of Medicine at Mount Sinai. “When we combine this finding with the knowledge that early intervention can lead to better outcomes for our Crohn’s patients, we have a truly relevant headline for a disease that has no cure.”
None of the identified protein biomarkers for Crohn’s was found to be predictive of ulcerative colitis.
In another study, titled “Association Between Early-life Exposures and Inflammatory Bowel Diseases, Based on Analyses of Deciduous Teeth,” Mount Sinai researchers in collaboration with colleagues in Portugal reported, for the first time, that exposure to certain metals, such as lead, copper, zinc, and chromium, early on in life — going back to the 25th week of pregnancy — may increase the risk of IBD.
The study was based on the analysis of baby teeth from 12 IBD patients, and 16 individuals who did not have the disease. Investigators analyzed baby teeth because teeth are capable of retaining information over time, and are an excellent source material to assess exposure to certain environmental factors, including heavy metals.
In the third study, titled “Deep Remission at 1 Year Prevents Progression of Early Crohn’s Disease,” researchers reported the findings of a Phase 3 trial called CALM (NCT01235689) showing that patients with moderate to severe Cronh’s entering in remission early on in the course of the disease had a 81% lower risk of disease progression over a median period of three years.
These observations were valid for patients kept on a tightly controlled therapeutic strategy (increased therapy based on symptoms and levels of inflammatory markers, such as calprotectin and C-reactive protein), and for those kept on standard therapy management.
The study was based on long-term follow-up data from 122 patients with Crohn’s who were recruited from 31 clinical sites.
“The data suggests strongly that achieving deep remission early in the course of Crohn’s disease can lead to disease modification with a significant decrease in long-term complications,” said Ryan Ungaro, MD, assistant professor of gastroenterology at the Icahn School of Medicine at Mount Sinai, member of the Feinstein IBD clinical center, and lead author of the study. “The implication is that we can play a big role in slowing the disease progression if we catch and treat Crohn’s early, highlighting the relevance of prediction and prevention in treating Crohn’s.”
In the last study, titled “Inflammatory Bowel Disease Clusters Within Affected Sibships in Ashkenazi Jewish Multiplex Families,” investigators found that in the Ashkenazi Jewish population, which is known to have a high prevalence of IBD, siblings with IBD tended to be clustered together sequentially, rather than being randomly distributed within the family.
Their findings were based on the analysis of 38 large Jewish families in which at least three first-degree family members had been diagnosed with IBD.
“The clustering of affected siblings suggests there are factors beyond genetics that lead to the development of IBD in these multiplex families, likely attributable to a shared environment,” said Elizabeth Spencer, MD, the study’s lead author, and an IBD fellow at the Icahn School of Medicine at Mount Sinai. “We are continuing to follow these families in an effort to pinpoint the precise factors. If we can identify these factors, we could alter them as a preventive measure for those at high risk of developing IBD.”
Given the fact that IBD has no cure, “our clinical strategy will center on aggressive and innovative mechanisms to predict and prevent the disease,” Colombel said.