Endogenous DNA damage accumulates in peripheral blood mononuclear cells of patients with systemic autoimmune diseases due to oxidative stress and epigenetically regulated DNA repair abnormalities.
Endogenous DNA damage accumulation in systemic autoimmune diseases contributes to genomic instability and aberrant immune responses, offering potential targets for understanding pathogenesis and developing new treatments.
The DNA damage response and repair (DDR/R) network, a sum of hierarchically structured signaling pathways that recognize and repair DNA damage, and the immune response to endogenous and/or exogenous threats, act synergistically to enhance cellular defense. On the other hand, a deregulated interplay between these systems underlines inflammatory diseases including malignancies and chronic systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Patients with these diseases are characterized by aberrant immune response to self-antigens with widespread production of autoantibodies and multiple-tissue injury, as well as by the presence of increased oxidative stress. Recent data demonstrate accumulation of endogenous DNA damage in peripheral blood mononuclear cells from these patients, which is related to (a) augmented DNA damage formation, at least partly due to the induction of oxidative stress, and (b) epigenetically regulated functional abnormalities of fundamental DNA repair mechanisms. Because endogenous DNA damage accumulation has serious consequences for cellular health, including genomic instability and enhancement of an aberrant immune response, these results can be exploited for understanding pathogenesis and progression of systemic autoimmune diseases, as well as for the development of new treatments.
Souliotis et al. (Fri,) conducted a review in Systemic autoimmune diseases (systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis). DNA damage response and oxidative stress was evaluated. Endogenous DNA damage accumulates in peripheral blood mononuclear cells of patients with systemic autoimmune diseases due to oxidative stress and epigenetically regulated DNA repair abnormalities.