Our work aims at the identification of new diagnostic and prognostic markers in rheumatoid arthritis (RA), using synovial biopsies in patients. We first demonstrated that the molecular signatures identified in these biopsies enable us to differentiate patients with early RA from patients suffering from other inflammatory conditions. Next, we performed transcriptomic studies in synovial biopsies harvested from patients with severe RA before and twelve weeks after initiation of TNF blocking or rituximab (depleting anti-CD20 antibody) therapy. These studies enabled us to identify specific molecular signatures targeted by these therapies in the synovium, and novel markers of response to therapy. Our results open interesting perspectives in terms of potential biomarkers, which could be used in order to improve diagnostic performances and therapeutic decisions based on individual molecular characteristics of the patients.