Serum Biomarkers Predict Crohn’s Disease Diagnosis 5 Years in Advance, but Not Ulcerative Colitis

Serum Biomarkers Predict Crohn’s Disease Diagnosis 5 Years in Advance, but Not Ulcerative Colitis

Monika Fischer, MD, reviewing Torres J, et al. Gastroenterology 2020 Mar 9.

Early intervention appears to be the key to mitigating severe complications of Crohn’s disease. Researchers for the Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study identified 51 proteins and antimicrobial antibodies that present in patients’ blood several years prior to the clinical diagnosis and have the potential to accurately identify individuals at risk.

Preclinical serum samples drawn from patients with Crohn’s disease or ulcerative colitis and healthy controls (n=200 each) were used to derive a predictive model for IBD that included hypothesis-driven antibodies and protein biomarkers. From each subject, 3 to 4 serum samples were retrieved: one around the date of diagnosis and others separated by about 2 years. 

A panel of protein biomarkers was predictive of Crohn´s disease within 5 years, with an area under the receiver operating curve (AUROC) of 0.76, and diagnosis within 1 year, with an AUROC of 0.87. The most consistent proteomic markers were those of inflammation and those involved in cytokine signaling, innate immunity, and response to bacteria. For ulcerative colitis, AUROC was only 0.56 within 5 years of diagnosis and 0.72 within 1 year.

PREDICTS is a landmark study toward being able to identify individuals at risk for developing Crohn’s disease. It appears that long before symptom onset, aberrant changes occur in the complement cascade, lysosomes, innate immune response, and glycosaminoglycan metabolism. 

We may have an early opportunity to intervene, but at this point, we do not know how. Can we change the microbiota via diet, antibiotics, probiotics, prebiotics, or a healthy lifestyle, or even introduce therapies prior to symptom onset to slow the overreactive immune response? 

Nevertheless, these results may help with a common case scenario: a symptomatic patient with a positive IBD panel but no endoscopic or histologic finding of inflammation. This patient is at risk of being diagnosed with Crohn’s disease in the foreseeable future. I suggest close follow-up that includes measurements of biomarkers of inflammation (serum and stool) and use of a low threshold in repeating endoscopic evaluation.

Monika Fischer, MD, FASGE


Torres J, Petralia F, Sato T, et al. Serum biomarkers identify patients who will develop inflammatory bowel diseases up to 5 y before diagnosis. Gastroenterology 2020 Mar 9. (Epub ahead of print) (

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