Increased levels of circulating DNA in patients with SAD
In our Tuesday class Dr Cohen mentioned that circulating DNA in the blood is on mechanism postulated as a causative factor in the autoimmune disease systemic lupus erythematosus (SLE). A recently published study from investigators in Italy supports this theory.
Results of studies investigating concentrations of circulating DNA have been contradictory. However, high concentrations of cell-free circulating DNA have been found in the serum or plasma of patients with systemic autoimmune disease (SAD), in particular SEL. Mechanisms postulated for this include apotosis, necrosis, or active cell release. Recently, attention has been given to the possibility of an alternative form of circulating nucleic acid acting as an autoantigen in SLE. DNA and RNA can be found in microparticles (MPs). Microparticles are membrane bound structures that generated by cell death. It has been hypothesized that these MPs act as adjuvants. MPs induce central B cell tolerance and stimulate peripheral autoreactive B cells.Through actions on B cells MPs may be considered a marker of cell activation with inflammatory markers. Recent studies have demonstrated increased levels of MPs in patients with SLE and primary Sjogren’s syndrome (SS).
The aim of the study was the evaluation of plasma DNA levels in patients with SLE and primary SS and the correlation of these levels with disease activity, disease damage and clinical manifestations. The study sample included 44 patients with SLE, 48 patients with SS, and 20 patients with rheumatoid arthritis (RA). The study showed that patients with SLE and SS have increased plasma levels of free DNA as compared to healthy individuals. However, while the levels correlated with disease activity in SS, the levels did not correlate with the level of disease activity in SLE. The authors state further investigation is needed with a larger sample population, standardized measurements and validated measures of disease.
Bartoloni, E., Ludovini, V., Alunno, A., Pistola, L., Bistoni, O., Crino, L., & Gerli, R. (2011). Increased levels of circulating DNA in patients with systemic autoimmune diseases: A possible marker of disease activity in Sjogren’s syndrome. Lupus, 20, 928-935.
I think it is interesting that people with SAD have elevated circulating DNA. The theory is that having this circulating DNA can lead to the formations of autoantibodies to the DNA and the subsequent autoimmune disorder. Could this possibly lead to a way to test and prevent SADs?
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