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Objective: to study the qualitative and quantitative composition of serum extracellular DNA (exDNA); apoptotic (nucleosomes) and necrotic fragmentation; complexification of monometinic proteins with exDNA; and the levels of exDNA methylation as compared to those of autoimmune and inflammatory markers in patients with rheumatic diseases (RD). Subjects and methods. One hundred and one patients, including 28 with rheumatoid arthritis (RA), 20 with systemic lupus erythematosus (SLE), 14 with ankylosing spondylitis (AS), 31 with scleroderma systematica (SDS), and 8 with other RDs, were examined. All the patients met the classification criteria accepted at the Research Institute of Rheumatology. A control group included 15 healthy individuals. The investigators studied the serum concentration of exDNA, the content of DNA fragments of different lengths and the monometinic protein complexified with DNA, the degree of DNA methylation, the levels of serum C-reactive protein (CRP) detectable by a high-sensitivity method, rheumatoid factor (RF), anti-DNA antibodies, and antinuclear antibodies (ANA).Results. 50-70% of the patients with RA, SLE, AS, and SDS were found to have elevated serum levels of exDNA, apoptotic and necrotic DNA; the degree of exDNA methylation (hypo- and hypermethylation) was altered. In SLE and SDS, exDNA hypomethylation was attended by autoimmune disorders: the presence of proper DNA autoantibodies and ANA. In RA, the high levels of exDNA methylation were associated with autoimmunity and inflammation (increased RF and CRP levels). In AS, the hypermethylation of apoptotic and necrotic DNA and monometinic proteins correlated with inflammatory activity and autoantigenicity (the appearance of ANA and anti-neutrophil antibodies).Conclusion. RDs are characterized by the higher concentration of apoptotic and necrotic DNA, impaired exDNA methylation, varying complexification of exDNA with monometinic proteins, which is associated with the hyperproduction of autoantibodies (including anti-exDNA antibodies) and inflammatory markers.

EXTRACELLULAR DNA AND THE LEVEL OF ITS METHYLATION IN DIFFERENT RHEUMATIC DISEASES