METABOLIC ALTERATIONS IN EARLY RHEUMATOID ARTHRITIS - from pathogenesis to treatment response

Inflammatory processes in rheumatoid arthritis (RA) are characterized by metabolic alterations.

The interest in the field has increased in the last years, as those alterations are therapeutically targetable, and their study may help identify metabolic biomarkers to predict treatment response in subjects with RA. However, a characterization of the altered metabolic pathways involved in RA development is still missing.

The goal of this project is to identify metabolic alterations associated with the early phases of RA pathogenesis and with response to anti-rheumatic treatment in patients with RA.Specifically, I aim to identify:- metabolic alterations in key cells in involved RA pathogenesis.

By studying fibroblast-like synoviocytes (FLS) obtained from healthy subjects after stimulation I will identify specific metabolites and metabolic pathways that are altered in FLS after activation.

I will also determine if the inhibition of those pathways suppresses FLS activation.- circulating factors, including metabolites, associated with the response to four different anti-rheumatic treatments in a large cohort of patients with early RA.

I will also create a prognostic score to predict the response to treatment in patients with early RA.The novelty of the project resides in the study of the metabolic alterations that occur in the early phases of RA development by using both in vitro data and clinical data from a large well-characterized cohort of patients with early RA.