We previously hypothesized that the sequence of transcribed region of human ribosomal repeats is selectively accumulated in circulating extracellular DNA due to its increased resistance to double-strand breaks caused by accumulation of single-chain breaks produced by nucleases. The contents of rDNA in blood serum DNA and in DNA from leukocytic nuclei both in healthy donors and in patients with rheumatoid arthritis were compared using dot hybridization method. By the content of non-methylated CpG-repeats, transcribed region of rDNA is identical to bacterial DNA, which is characterized by potent immunostimulatory effect. The transcribed region of rDNA (13.3 kb) contains more than 200 CpG-motifs capable of interacting with TLR9 receptors, which are the mediators of the cell immune response to the action of CpG-rich DNA fragments. The data suggest that DNA from dead cells circulating in the peripheral blood is enriched with sequences possessing potent immunostimulatory properties.

Fragments from the transcribed region of the ribosomal repeat include considerable amounts of unmethylated CpG DNA motifs. These motifs activate immune cells via the interaction with Toll receptors. In vitro experiments confirmed the stimulatory effect of transcribed region of ribosomal repeat on human lymphocytes. Culturing of lymphocytes in a medium containing 2–20,000 ng/ml fragments from transcribed region of ribosomal repeat was accompanied by structural changes in the nucleus in a considerable number of cells. These changes manifested in translocation of pericentromeric heterochromatin from the membrane to the center of the nucleus and activation of the nucleolus and were accompanied by a significant increase in interleukin-6 production and slight stimulation of tumor necrosis factor-α synthesis. The transcribed region of the ribosomal repeat and E. coli DNA had various effects on quantitative parameters of lymphocytes. Our results suggest the existence of mechanisms of stimulation not mediated by the interaction of CpG DNA motifs with Toll receptors.

A study was done regarding the effect of the oxidizing agent potassium chromate (K 2 CrO 4 , PC) on cultured dermal fibroblasts of a healthy donor and three patients with rheumatoid arthritis (RA). Characteristics of the rRNA gene (RG) complex—RG copy number, active RG (ARG) dosage, and 18S rRNA content—were determined for each cell line. In cells of the healthy donor, oxidative stress caused by low doses of PC (2–4 µM, 1–4 h) induced an early response, including a 50–80% increase in total RNA and rRNA. An appreciable activation of the nucleolus was observed cytochemically, by silver staining and morphometry. The early response grew considerably lower with the increasing passage number and/or PC concentration. Exposure to 6–12 µM PC for 24 h led to a progressively increasing cell death rate (late response). The existence and intensity of the early response correlated positively with cell survival during further culturing. Cells of the RA patients displayed almost no early response even at early passages: total RNA did not increase, and rRNA increased by no more than 10%. Cell disruption (apoptosis) during further culturing was more intense than in the line originating from the healthy donor. The apoptosis intensity characterized by the increase in the content of DNA fragments in the culture medium and in the caspase 3 activity was inversely proportional to the ARG dosage in the genome. The results provide the first quantitative characterization of the early and late responses of cells to PC-induced oxidative stress and suggest the role of ARG dosage in cell survival during stress.

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During 1995-1999 autumn-winter periods 300 teenagers with signs of acute respiratory disease (ARD) were examined. 38% from them had group A p-hemolytic streptococcus (GABS) and elevation of anti- streptolysine-O antibodies titers what comply with definite streptococcal infection criteria. Arthritis was revealed and immunologically characterized in 35 teenagers with streptococcal pharyngitis. Pts with non streptococcal pharingitis did not have arthritis. These results allowed to describe clinical and immunological signs of poststreptococcal arthritis for the first time in our land. These signs included asymmetrical non migrating arthritis lasting from 8 to 156 days with primary involvement of large (knee) and less frequently - small joints. Synovitis manifested with joint pain and swelling. It was confirmed by US examination and differed from migrating arthritis in acute rheumatic fever (ARF). According to WHO recommendations teenagers with definite streptococcal infection received combined treatment - single injection of bicillin-5 with subsequent treatment with fenoximethylpenicilline. Cultures and blood immunologic examination in a month and later after treatment gave negative results in 90,5% of pts. Described disease or syndrome associated with acute upper respiratory infection in teenagers differ from ARF.

A total of 216 patients with rheumatic fever and rheumatic heart from the Institute of Rheumatology and 126 patients with rheumatic heart diseases alone from the Center of Cardiosurgery were clinically and immunologically studied. The immunological study included the detection of b-hemolytic group A streptococcus, O-antistreptolysin, the measurement of C-reactive protein, immunoglobulins, C3, C4, Ciq-binding, anticardiolipin antibodies, etc. The findings indicated that the secondary penicillin prophylaxis prevents streptococcal pharyngitis and recurrence of acute rheumatic fever after 5 years. The high levels of Ciq-binding and anticardiolipin antibodies were directly proportional to the incidence rates of acute endocarditis and associated with the occurrence of venous and arterial thromboses.

Based on clinico-immunologic studies subtypes of systemic lupus erythematosus (SLE) were distinguished. The ANF-R++H-DNA-CH50 variant determines acute onset of SLE with renal injury in the form of diffuse glomerulonephritis. The ANF-Sp-RNP-RF mirrors the development of Raynaud's syndrome, Sjögren's syndrome, polymyositis, pneumosclerosis and myocarditis. The ANF-Sp-Ro-RF variant is associated with skin derangement in the form of discoid foci, anular, papulosquamous eruption, vitiligo, hyperpigmentation, and cerebrovasculitis. The Ro-anti-Po, La-anti-La system is related to the idea of SLE, seronegative in accordance with ANF, when rat liver sections are used as a substrate in immunofluorescence.

The authors consider that the development of immunopathological reactions in SLE, AIDS depends on the reduction in normal gamma-globulin level in the patient's serum. The sera with anti-DNA, anti-HIV antibodies show a decreased binding of corresponding antigens and decreased concentrations of gamma-globulin with normal features.

Methods are described that are used for the titration of antinuclear, anticentromere, and anti-Scl-70 antibodies in systemic scleroderma, systemic lupus erythematosus, and rheumatoid arthritis: indirect immunofluorescence with various antigenic substrates (sections of fresh-frozen rat liver and Hep-2 cell culture), counter-current immunoelectrophoresis, isolation of Scl-70 antigen. Use of Hep-2 cells as a substrate for indirect immunofluorescence was found clinically and diagnostically more effective since it permitted the detection of anticentromere antibodies and anti-Scl-70. Nucleolar, mottled, homogeneous, marginal immunofluorescence types were observed when rat liver sections and Hep-2 cells were used for substrates. Anticentromere antibodies and anti-Scl-70 were isolated significantly more frequently in systemic lupus erythematosus or rheumatoid arthritis.

A total of 104 patients with scleroderma were examined. Anticardiolipin antibodies were detected in 37.5 per cent of the patients with systemic scleroderma and in 3 per cent of healthy individuals; they were more often detected in 46.8 per cent of the patients with diffuse affections of the skin, atherosclerosis, Raynaud's syndrome accompanied by ulcero-necrotic affections of the skin as compared to patients with restricted affections of the skin (sclerodactylia and focal scleroderma)--29.8 per cent. No significant changes in the frequency of detecting a rheumatic factor, antibodies to Scl-70 were revealed in subgroups of patients with scleroderma, positive and negative anticardiolipin antibodies. Of the greatest interest is a significant difference in levels of C-reactive protein which were high in half of the patients with anticardiolipin antibodies. Anticentromere antibodies were detected twice as more often in patients without anticardiolipin antibodies that corresponded to systemic sclerodermia with minimum involvement of the skin into the pathological process. It is suggested that ulcero-necrotic affection of the skin in systemic sclerodermia is associated with C-reactive protein but it is not of an immunocomplex nature.