Predictive biomarkers for response to treatment in inflammatory bowel disease

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic disorder involving a pathological response of the immune system, resulting in chronic inflammation of the gastrointestinal tract. Currently, there is no curative treatment, so the therapeutic goal is to control the inflammatory process to prevent the onset of symptoms and the development of complications. To achieve this goal in the most severe or refractory cases, biologic agents and JAK-inhibitors are the main therapeutic options. However, such treatments only induce remission in 1/3 of patients. Moreover, it is not possible to predict which patients will benefit from the use of the various biological drugs currently available. The identification of biomarkers predictive of response to treatment is, therefore, imperative for the management and treatment of this disease.

In this project, we will identify novel biomarkers of clinical response to the different available therapies, hence allowing the development of an individualized medicine where each patient would be treated with the most appropriate therapy given its unique profile. To that aim, the specific aims of this project will be:

1. To characterize the mucosal immune infiltrate and their circulating precursors, together with the proteomic profile of the tissue and serum extracellular vesicles (EVs), in IBD patients and healthy controls.

2. To identify tissue and blood biomarkers to predict clinical response to the current biological therapies and JAK-inhibitors in IBD.

3. To identify the immune cell subset(s) and the signalling pathways modulated by each of the treatments in responding IBD patients.

4. To determine the presence and severity of endoscopic inflammation by non-invasive approaches, before starting treatment and at the end of the follow-up period