Current therapeutic leads for the treatment of autoimmune diseases: stem cell transplantation and inhibition of post-translational modifications of autoantigens

Abstract

Background: The complexity of autoimmune diseases is reflected on their clinicopathological heterogeneity and the failure to find treatments that cure them after over a century of research. Conventional treatments help ameliorate disease activity but they treat the symptoms whereas the diseases remain incurable in the vast majority of patients. Objective: To confront diseases of such nature it is essential to discover therapeutics that will lead to the induction of tolerance or the specific deletion of autoreactive lymphocytes. Current basic and clinical research strategies focus on the better identification of self-antigens, the induction of T regulatory cells that can suppress autoreactive cell activities or, more radically, the ‘reformatting’ of the immune system through hematopoietic stem cell transplantation (HSCT). Methods: We analyzed literature on autoimmune disease therapeutics, focusing on new antigens that may arise from post-translational modifications of common proteins and, also, the area of HSCT. Results/conclusions: With the recent discovery that citrullination of self-epitopes may be a major pathogenic mechanism for, at least, certain types of autoimmune diseases, it becomes apparent that potentially any self-antigen in the body can be a target of an autoimmune attack. In addition, although the available data on HSCT applied to patients suffering from severe refractory autoimmune diseases do not allow for the determination of the efficacy of the various methods employed to re-educate the immune system, they contribute to our understanding of disease pathogenesis and the improvement on the therapeutic approaches.