Validation of blood biomarkers predicting relapse in Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) mostly localised in terminal ileum (distal part of the small intestine) and colon. This incurable disease evolves through phases of inflammatory flare-ups, interspersed with phases of remission. The chronicity of this intermittent behaviour carries the risk of serious complications (e.g. intestinal perforation, fibrosis and cancer).
The administration of antibodies directed against a pro-inflammatory protein (tumor necrosis factors-α: TNF-α) has become the cornerstone of Crohn's disease treatments. Once remission is achieved, anti-TNF-α withdrawal may be contemplated for different reasons: safety concerns, healthcare costs and patient preference. However, as relapse remains largely unpredictable, anti-TNF-α withdrawal is not currently recommended. In this context, the search for biomarkers predicting relapse is a priority for patients and clinicians. More generally, the ability to anticipate the future of patients is a key element in the development of personalized medicine.
In 2020 and 2022, the team from the Laboratory of Translational Gastroenterology (GIGA Institute) discovered blood biomarkers predicting short-term (< 6 months) and mid/long-term (> 6 months) relapse in patients with Crohn's disease stopping anti-TNF-α therapy (STORI cohort) (Pierre N. et al., Gut 2020 and Gut 2022).
Thanks to a new study of the Laboratory of Translational Gastroenterology, the interest of some fifteen of these biomarkers has been confirmed by analysis of an independent cohort (SPARE). These biomarkers might pave the way for detecting the early phase of Crohn’s disease reactivation and, by doing so, they could support or discourage the decision of anti-TNF-α withdrawal.
The study required interdisciplinary collaboration. Setting up the cohort was part of the European H2020 Biocycle project, it involved 64 centers in Europe and Australia. The validation of biomarkers relied in particular on the development of a proteomics technology (selected reaction monitoring) using mass spectrometry. This technique, developed in collaboration with the GIGA-Proteomics platform and the Laboratory of Mass Spectrometry at the University of Liège, enabled the precise and simultaneous measurement of 70 proteins in the blood of around 300 patients. Finally, data analysis was carried out in collaboration with the Department of Electrical Engineering and Computer Science (Montefiore institute, University of Liège).
Source
External validation of serum biomarkers predicting short-term and mid/long-term relapse in patients with Crohn's disease stopping infliximab
Nicolas Pierre, Vân Anh Huynh-Thu, Dominique Baiwir, Gabriel Mazzucchelli, Maximilien Fléron, Lisette Trzpiot, Gauthier Eppe, Edwin De Pauw, David Laharie, Jack Satsangi, Peter Bossuyt, Lucine Vuitton, Sophie Vieujean, Jean-Frédéric Colombel, Marie-Alice Meuwis, Edouard Louis, GETAID and the SPARE-Biocycle research group.
Gut, 2024.
