Predict to prevent Targeting adaptive immune responses to decrease the risk of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease which can lead to severe disability, loss of work, and even premature death if not treated adequately. Although many treatment s ware now available, they are often costly and not curative, and a substantial percentage of patients don’t respond completely to treatment. As a results, RA management has a big economical and societal impact.
One possible approach to reduce disease burden is RA prevention in the pre-clinical stage, when individuals have noy yet manifested specific signs and symptoms. However, in order to prevent RA in at-risk individuals, it is necessary to identify those subjects with the highest risk of progression and for whom preventive treatment might be beneficial. Moreover, there is a need to identify which treatment is most effective in disease progression, with limited side effects.
The aim of this thesis was to evaluate which risk factors could be used in clinical practice for the identification of individuals with the highest risk of developing RA, who might benefit from treatment strategies aimed to prevent disease progression and improve perceived disease burden. We proposed a small mechanistic interventional study to evaluate the effect of preventive treatment on immune system alterations present in RA-risk individuals, to better understand disease pathogenesis and treatment effect. Moreover, we isolated autoreactive B cells from anti-citrullinated protein antibody (ACPA)-positive RA patients and investigated the effect of small molecule inhibitors targeting relevant pathways of B cell differentiation and maturation altered in RA.