Objective. To reveal changes of CD+CD25+FoxP3+ T-regulatory cells (T-reg) number in pts with systemic lupus erythematosus (SLE) receiving rituximab and to assess relationship T reg content with changes of disease activity and serum autoantibodies level during treatment. Material and methods. 12 pts with definite SLE were included. Pts were examined before treatment, after 1, 3 and 6 months. Besides routine laboratory tests anti-double-stranded DNA antibodies, B lymphocytes and T reg cells number was evaluated with flow-cytometry. SLE activity was assessed with SLEDAI 2K scale. Rituximab 500 mg was administered every week iv during 4 weeks. 4 pts received combined treatment with cyclophosphan. Results. Mean age of pts was 30,5±9,8 years (Me 31 years, varied from 18 to 49 years), disease duration varied from 7 to 148 months. T reg number before treatment was not decreased and did not correlated with anti-DNA antibodies level. T reg markers (Foxp3+, CD25+, CD4+CD25+) changes and values of SLE activity on SLEDAI 2K after the end of treatment correlated with presence of clinical response to treatment with rituximab in 3 months. Binary logistic regression model including 4 above mentioned predictors in total allows predicting correctly clinical response to therapy in 83% of cases. Conclusion. Changes of CD25+, CD4+CD25+, CD4+CD25+FoxP3+ T-cells number immediately after the end of treatment with rituximab correlated with clinical effect of the treatment and determined subsequent response to anti-B cell therapy.

Objective. To study clinical significance of proinflammatory cytokines (tumor necrosis factor α – TNFα, interleukine 6 – IL6, IL18), soluble receptors of TNFα (sTNF-R), anti- inflammatory cytokines (IL10) and integral marker of cytokine-dependent cell immune response activation neopterin in antiphospholipid syndrome (APS).Material and methods. Serum concentration of cytokines and neopterin was evaluated by immunoenzyme assay with commercial kits “BioSource International, Inc.” (USA), “Bender MedSystems” (Austria) and “IBL” (Germany) in 39 pts with primary APS (PAPS), 53 pts with secondary APS (SAPS) associated with systemic lupus erythematosus (SLE), 164 pts with SLE and 54 healthy donors.Results. Level of Th1 cytokines (TNFα, IL18), sTNF-R and neopterin in PAPS, SAPS and SLE as well as Th2 cytokines (IL6, IL10) in SAPS and SLE were significantly higher than in donors (p<0,05). TNFα elevation in PAPS was associated with damage of cardiac valves (p<0,05) and CNS (p<0,01), IL18 elevation – with chronic leg ulcers (p<0,001). Most prominent sTNFα-R elevation in SAPS was revealed in pts with thrombocytopenia (p<0,05). Neopterin hyperproduction in APS was associated with cardiac valve damage16 (p<0,001). IL10 level elevation in APS correlated with decreased thrombosis history (r=- 0,4; p<0,02), in SLE with APS – with decrease of damage score SLICC (r=-0,7; p<0,001) what proves protective significance of IL10 in relation to thrombosis development and disease progression. Increased concentration of IL 18 was associated with atherogenic disturbances presented as hypertrigliceridemia (r=0,6; p<0,01) and decrease of HDLP cholesterol (r—0,4; p<0,01). Positive correlation between TNFα, IL6 and neopterin level, IgM anticardiolipine antibodies and IgG/IgM antiprothrombin antibodies (p<0,05) was revealed. Cytokine, sTNFα-R and neopterin level elevation in SLE with APS was associated with increase of SLEDAI and ECLAM activity indices (p<0,05). Conclusion. Cytokine and neopterin hyperproduction reflecting cell immunity activation and inflammation is an important factor of APS pathogenesis.

Objective. To assess participation of tubulointerstitial and glomerular components in renal damage progression in pts with systemic lupus erythematosus (SLE) using immuno-morphological data. Material and methods. 45 SLE pts with lupus nephritis, 34 pts with chronic glomerulonephritis (CGN), 19 pts with drug induced chronic tubulointerstitial nephritis (DCTN) and 30 control persons were included. Concentration of anti-DNA antibodies, C-reactive protein (CRP), transforming growth factor β (TGFβ), tumor necrosis factor α (TNFα), monocytic chemotactic protein 1 (MCP1) was evaluated by immunoenzyme assay. Morphological examination of renal biopsies with semiqantitative assessment of measures reflecting process activity, sclerosis and renal blood vessels changes was performed. Results. Elevated concentration of TNFα and CRP was revealed in pts with SLE, CGN and DCTN. Pts with DCTN had highest, pts with CGN – lowest and SLE pts – intermediate values of these measures. There was a clear tendency of TNFα elevation with increase of SLE activity. Pts with lupus nephritis and DCTN had high values of MCP1. TGFβ level was significantly decreased in SLE. Glomerular component of lupus nephritis was characterized mainly by moderate proliferation and sclerosis while tubulointerstitial component signs were prominent. Conclusion. Further examination of tubulointerstitial changes, MCP1 and TGFβ appear to be worthwhile.

Objective. To characterize specters of common and modified lipoproteins (LP) in serum of pts with rheumatoid arthritis (RA) according to age and sex and compare with healthy donors (with normal lipid level). Material and methods. 103 pts with RA (88 female and 15 male) aged 21 to 69 years were included. Specters of common and modified LP in serum and plasma were evaluated with small-angle x-ray scattering. Results. Low level of intermediate density lipoproteins (IDLP) subfractions and very low density lipoproteins (VLDLP) as well as high level of low density lipoproteins (LDLP)30 was revealed in pts with RA. Mean level of LP modification was about 60%. High density lipoproteins (HDLP) subfraction was least and IDLP subfraction – most susceptible to modification. LP modification level increased due to LDLP and VLDLP fractions. This level had a tendency to increase with age because of elevation of atherogenic LP part. Mean values of common LP did not differ between sex and age groups of pts with RA. Unexpectedly low (in comparison with normal lipid content) level of LP modification of the whole fraction of HDLP was the feature of modified LP specter in pts with RA. Conclusion. Level of common and modified LP in blood plasma and serum of RA pts is connected with general state of lipid metabolism and immune defense factors balance. Low level of VLDLP cholesterol and high level of LDLP cholesterol as well as high degree of LP of these fractions modification may be probably considered as markers of RA activity.

Diagnosis of rheumatoid arthritis (RA) at the beginning of the disease is a difficult task especially due to presence of a large group of pts with “undifferentiated arthritis” (UA) i.e. with inflammation of one or more joints which does not comply with a definite nosology. According to clinical experience UA is quite a serious condition which during a year transforms in definite RA in at least one third of pts. In 2007 Van der Helm-van Mil et al. proposed special criteria (“prediction rule”) allowing predicting transforming UA intoRA by counting prognostic index (PI). PI6 means low and PI8 - high probability of RA 37development during 1 year. Objective. To assess possibility of using prognostic criteria for determination of transforma- tion of UA into RA in Russian pts. Material and methods. 93 pts (84,9% - female) with early (disease duration no more than 12 months) UA were included. Mean age was 44,3±15,2 years, mean disease duration – 128,9±82,1 days (4,3±2,7 months). 59,1% of pts had olygoarthritis, 26,9% were rheumatoid factor seropositive, anti-cyclic citrullinated peptide antibodies (ACCP) were revealed in 29%. Examination with above mentioned methods to specify the diagnosis was performed trice during 12 months: at baseline, after 6 and 12 months. Results. During a year of follow up RA developed in 39(41,9%) pts. Mean value of PI was 5,18±2,48 (median 5,02 [3,01; 7,02]). PI values in pts with disease transformation into RA during a year were significantly higher (6,55±2,33) than in the rest of pts (4,18±2,1), p<0,0001. Analysis of discriminatory curve (ROC) was performed. Area under the curve statistics was 0,77 (SE 0,048, p=0,0001, 95% confidence intervals 0,68; 0,87). 64 (68,8%)pts had PI6, 17(18,3%) - PI≥8 and 12 (12,9%) – PI between 6 and 8. 17(26,6%) pts with PI≥6, 13 (76,5%) pts with PI≥8 and 9 (75%) pts with PI between 6 and 8 fulfilled criteria of RA in a year. Published data on European pts with UA cohorts analysis were compared with results of the present study. Conclusion. Using prognosis criteria for pts with UA in Russian pts gave satisfactory result. ROC analysis revealed PI level dividing transforming and not transforming into RA pts not around 8 as was demonstrated earlier but around 6. Differences between results of the present study and published data may be due to different factors including genetic features as well as clinical heterogeneity of pt groups from Western and Eastern Europe.

Objective. To assess frequency of adverse events during short term administration of gluco- corticoid (GC) in protracted and chronic gout arthritis. Material and methods. 59 pts with tophaceous gout (crystal-verified diagnosis) and arthritis of three and more joints lasting more than a months in spite of treatment with sufficient doses of nonsteroidal anti-inflammatory drugs were included. Median age of pts was 56 [48;63], median disease duration – 15,2 years [7,4;20], median swollen joint count at the examination – 8 [5;11]. The patients were randomized into 2 groups. Methylprednisolone (MP) 500 mg/day iv during 2 days and placebo im once was administered in one of them, betamethasone (BM) 7 mg im once and placebo iv twice – in the other. Clinical evaluation of inflamed joints was performed every day. Standard laboratory examination and ECG were done before drug administration, at 3rd, 7th, and 14th day of follow up. Immunoreactive insulin level was evaluated before drug administration and at day 14. Blood pressure (BP) was measured every day. Results. After first GC administration BP elevated in 28 (47%) pts. In pts not having appropriate BP values BP elevated in 73% of cases. Pts with appropriate BP values showed less frequent BP elevation – 38% (p=0,02). In 8 (13%) pts at day 3 after GC administration ECG signs of myocardial blood supply deterioration were revealed. Glucose level elevated in 10 (17%) pts and after the second BM administration – in 5 (8%) pts. Cholesterol level did not significantly change after 14 days of follow up but in 28 (47%) pts it increased in comparison with baseline. Trigliceride level significantly decreased at day 14 from 149 [106; 187] to 108 [66,5; 172] mg/dl (p=0,02). 26 (44%) pts had face hyperemia, 4 (7%) –42 palpitation and 2 (3,4%) – bitter taste. Conclusion. Administration of short course of GC in pts with gout requires monitoring of possible adverse events. Antihypertensive therapy providing appropriate BP level decreases frequency of BP elevation.

A case of an unusual course of AA-amyloidosis in a pt with rheumatoid arthritis – disseminated amyloid deposition in lungs, heart and liver with insignificant and variable proteinuria – is presented