Discovery of new blood biomarkers for the management of patients with Crohn's disease
The team from the Laboratory of Translational Gastroenterology in collaboration with the GIGA-Proteomics platform and the Mass Spectrometry Laboratory has identified blood biomarkers with significant potential in the prediction of recurrence of Crohn's disease following discontinuation chronic treatment. These results have just been published in the scientific journal Gut.
Objective A subset of Crohn’s disease (CD) patients experiences mid/long-term remission after infliximab withdrawal. Biomarkers are needed to identify those patients.
Design New biomarkers of relapse were searched in the baseline serum of CD patients stopping infliximab when they were under combined therapy (antimetabolite and infliximab) and stable clinical remission (diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors cohort, n=102). From shotgun proteomics experiment (discovery step), biomarker candidates were identified and further targeted by selected reaction monitoring (verification step). The dataset was stratified to search for markers of short-term (<6 months) or mid/long-term relapse (>6 months). The risk of relapse and the predicting capacity associated with biomarker candidates were evaluated using univariate Cox model and log-rank statistic, respectively. To test their complementary predicting capacity, biomarker candidates were systematically combined in pairs.
Results Distinct biomarker candidates were associated with the risk (HR) of short-term (15 proteins, 2.9<HR<16.1, p<0.05) and mid/long-term (17 proteins, 2.1<HR<4.7, p<0.05) relapse, they reflect different pathophysiological processes. In stratified and non-stratified datasets, novel marker combinations exhibited a high predicting capacity as shown by their higher Z-scores (false discovery rate <0.001) than C reactive protein and faecal calprotectin (current references in predicting relapse).
Conclusion We identified for the first time circulating biomarker candidates associated with the risk of mid/long-term relapse in CD patients stopping infliximab. We also highlight a sequence of pathophysiological processes leading to relapse, this could help to better understand the disease progression. Our findings may pave the way for a better non-invasive evaluation of the risk of relapse when contemplating antitumour necrosis factor α withdrawal in CD patients.
Nicolas Pierre, Dominique Baiwir, Vân Anh Huynh-Thu, Gabriel Mazzucchelli, Nicolas Smargiasso, Edwin De Pauw, Yoram Bouhnik, David Laharie, Jean-Frédéric Colombel, Marie-Alice Meuwis, Edouard Louis, GETAID (Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif)