Ricerc@Sapienza

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by autoantibodies production as a result of the breakage of immunological tolerance mechanisms. Different immune cell types including lymphocytes take part in both joints-restricted and extra-articular manifestations of the disease.
Autophagy is an evolutionarily conserved lysosomal degradation pathway involved in different aspects of lymphocytes functionality. It has been demonstrated that the relation between autophagy and apoptosis influences the survival and inflammatory potential of peripheral cells from RA patients. Besides, IL-6, one of the most relevant cytokines in RA pathogenesis, was found to stimulate autophagy in B cells suggesting an involvement of autophagy in the inflammatory events of the disease.
Similarity in serum cytokines panel of RA patients and patients affected by CoronaVirus Disease 19 (CoViD 19) has been recently demonstrated, suggesting that some immune-mediated mechanisms might be common to both. Several anti-rheumatic drugs, including IL-6 antagonist Tocilizumab, used to treat patients affected by RA, are now proposed for the treatment of Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2).
We hypothesize that autophagy dysregulation may have a role in the activation and functions of lymphocytes during conditions characterized by excessive inflammation and cytokines production such as RA as well as CoViD 19 infection. To this aim, we will evaluate ex vivo autophagy and apoptosis in lymphocytes subsets from patients with RA and CoViD 19 infection before and after therapy with anti-IL6 drug Tocilizumab.
The results of this study will provide important experimental evidences for the possible use of existing drugs targeting the autophagy pathway as a new therapeutic strategy against inflammatory disorders and for the control of future epidemic of SARS-CoV-2 infection.