Soluble Fas Ligand, an overlooked target of therapy in dermatological and non-dermatological conditions

Background: The Fas/Fas Ligand (Fas/FasL) system mediates key physiological and pathological pathways. Therapies targeting this system are currently unavailable due to the complexity of the Fas/FasL pathway and the side effects associated with reduced apoptosis of cancer cells and the lack of regulation of the immune system. PC111 is a human monoclonal antibody that uniquely targets the soluble (s) but not the membrane-bound (m) FasL, the latter being responsible for immunosurveillance and cancer; the selective mode of action of PC111 precludes its interference with the latter mechanisms. We showed previously that selective blocking soluble FasL (sFasL) could be an effective non-immunosuppressive treatment in mouse models of Pemphigus (PV) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN). Aim: To identify additional diseases where sFasL is elevated and potentially involved in their pathogenesis. Findings: sFasL is up regulated in drug reaction with eosinophilia and systemic symptoms. Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjogren syndrome also have elevated levels of sFasL that are involved in some of the mechanisms underlying the diseases. Finally, sFasL is elevated in the bronchoalveolar lavage (BAL) and plasma of Acute Respiratory Distress Syndrome, while blocking sFasL reverses apoptosis in lung epithelial cells, thus reducing mortality. Conclusion: By selectively blocking sFasL, one could potentially modify the course of several diseases.