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Inflammatory protein biomarkers elevated several years before ulcerative colitis diagnosis

17th August 2021

Patient blood samples several years before developing ulcerative colitis indicated elevated levels of inflammatory protein biomarkers.

Ulcerative colitis is a bowel disease characterised by inflammation in the large bowel and rectum. It is a chronic, relapsing, remitting disease with an estimated prevalence of 9 to 20 cases per 100,000 people per year and which causes diarrhoea, abdominal pain and rectal bleeding. While the underlying aetiology is uncertain, it is believed to arise from exposure to environmental triggers in susceptible individuals. Furthermore, it is widely accepted that treating the disease at an earlier stage is the preferred strategy, particularly as once the diagnosis is established, bowel damage is already present in the majority of patients highlighting the need to identify possible early disease markers. Though research has already identified several inflammatory protein biomarkers that are predictive of Crohn’s disease within 5 years, there are currently no known relevant protein biomarkers for ulcerative colitis.

In trying to identify any such relevant protein biomarkers, a team from the Department of Gastroenterology, Faculty of Medicine and Health, Orebro University, Sweden, performed a case-control study comparing pre-diagnostic plasma samples of those who later developed ulcerative colitis (cases) with those who remained free of the disease (controls). In an effort to determine the influence of genetics and environmental factors, the researchers also examined twin pairs and healthy controls. The team used principal component analysis to identify specific proteins that were elevated in either case or control patients.

Findings
The researchers focused on 92 different potential protein biomarkers and obtained pre-diagnostic plasma samples from 72 individuals who later developed ulcerative colitis and 140 matched healthy controls. The median age of both case and control cohorts was 50 years (47% male) and the median time from when the pre-diagnostic samples were taken before diagnosis was 4.8 years. Analysis of the protein biomarkers revealed a total of six specific proteins that differentiated between cases and controls (p < 0.05) and which remained significantly elevated (after adjustments for age, sex and smoking status). An analysis of the area under the receiver operating curves showed that these six proteins had a valve of 0.92. Among the of twin samples, only four of these six proteins were discriminatory for ulcerative colitis.

In a discussion of their findings, the authors highlighted the importance of identifying predictive signatures for ulcerative colitis and concluded that the up-regulation of these six protein biomarkers were highly predictive of the subsequent development of ulcerative colitis and concluded that this provided a novel means of identifying patients who were likely to develop the disease in the future.

Citation
Bergemalm D et al. Systemic inflammation in pre-clinical ulcerative colitis. Gastroenterology 2021