Purpose of the study. Comparative study of the phenotypic and functional properties of dendritic cells (DC) in groups of patients with rheumatoid arthritis (RA) receiving disease-modifying drugs, or biological drugs and (or) pulse therapy with high doses of glucocorticoids.Materials and methods. The study included 39 patients with RA and 20 age-appropriate and semihealthy donors. Nineteen patients were treated with standard disease-modifying drugs (BMP) in the form of monotherapy or in combination (group PA1) at the time of the examination, 20 – biological preparations or pulse-therapy with glucocorticoids (group PA2). In the latter case, the examination was carried out for 2–7 days after the last injection of methylprednisolone.Results. In this study, the properties of DC generated from monocytes under the action of IFN-α (IFN-DK) for RA are described for the first time. It has been established that the general feature of DC in the PA1 and PA2 groups are signs of immaturity of the DC, manifested by increased CD14 expression and a decrease in the proportion of mature (CD14-CD83 +) DC. Despite the differences in DC in the PA1 and PA2 groups, both cell types retain in vitro sensitivity to dexamethasone, the treatment of which leads to a significant inhibition of TNF-α production and a decrease in allostimulant activity of the DC. Thus, IFN-DK in RA patients receiving medical therapy is characterized by the presence of tolerogenic properties, which are most pronounced when used in a program of treatment of biological agents or pulse therapy with corticosteroids.

Abstract. The aim of this study was to elucidate a role of brain hemispheres in formation of rheumatoid arthritis (RA). The parameters of higher nervous activity, autonomous and immune systems in these patients that were characterized by domination of the left or right hemispheres of a brain, were defined in present work. The results of this work allow of justifying the following items: a) relative increase in functional activity of right brain hemisphere in woman may represent a factor that either contributes to triggering of rheumatoid arthritis, or predisposes for its development; b) formation of rheumatoid arthritis in females is accompanied by complex changes in psychophysiological and immune parameters, that exhibit significant features depending on functional asymmetry of the hemispheres; c) a pronounced dependence is revealed between clinical course of disease and functional asymmetry of hemispheres.

Abstract. Present study deals with size measurements of telomeric DNA from the human peripheral mononuclear immune cells in rheumatoid arthritis (RA). A method for measuring the relative telomere length by in situ hybridization followed by flow cytometric analysis (flow-FISH) was used. Relative telomere length (RTL) in monocytes was estimated as mean fluorescence intensity (MFI) of test cells divided by MFI values of internal control cells. Hybridization conditions for analysis of telomere length in monocytes have been optimized in advance. It has been shown that RTL of monocytes was significantly lower in RA patients compared to donors. Significant differences in telomere length of monocytes between RA patients and donors were revealed for the young persons under 30 years old. The findings obtained may be considered as an additional argument confirming the hypothesis on genetic defects of hematopoietic stem cells determining RA development.

Abstract. Present study deals with size measurements of telomeric DNA from the human peripheral mononuclear immune cells in rheumatoid arthritis (RA). A method for measuring the relative telomere length by in situ hybridization followed by flow cytometric analysis (flow-FISH) was used. Relative telomere length (RTL) in monocytes was estimated as mean fluorescence intensity (MFI) of test cells divided by MFI values of internal control cells. Hybridization conditions for analysis of telomere length in monocytes have been optimized in advance. It has been shown that RTL of monocytes was significantly lower in RA patients compared to donors. Significant differences in telomere length of monocytes between RA patients and donors were revealed for the young persons under 30 years old. The findings obtained may be considered as an additional argument confirming the hypothesis on genetic defects of hematopoietic stem cells determining RA development.

Abstract. The aim of the investigation was to study the immunological characteristics of RA patients with anaemia. Clinical and laboratory data including the percentage of the main lymphocyte subclasses, phagocyte and DTH-effector activity, serum concentration of immunoglobulins, the percentage of cells producing IFNγ and/or IL-4 and percent of monocytes producing TNF. We revealed some significant clinical, laboratory and immunological differences between RA patients and healthy donors and between patients with and without anaemia. Our data demonstrate RA anemic patients to have more severe disorders than patients without anaemia. We also revealed some significant immunological differences between RA patients and healthy donors and between patients with and without anaemia, including percent of cells producing IFNγ and/or IL-4. Our data permit to conclude that RA patients have many different immunological disturbances, more severe in anaemic patients.

We investigated the long&term outcomes of high&dose immunosupression and autologous hematopoietic stem cell transplantation (HSCT) vs continuing the currently accepted standard of care in severe, refractory systemic lupus erythematosus (SLE). Fifteen patients, who underwent high-dose immunosupression and HSCT and fifteen patients who continued the currently accepted standard of care, were observed. The median follow up is 45±10,4 months. Complete remission was achieved in six patients (40%), in another six patients (40%) decrease of SLEDAI was registered. Relapse occurred in 7 patients (47%). Transplant-related mortality was 13% (2/15). Overall 5-years survival was 80%. Disease-free 5-years survival was 20%. Another 3 patients died after 2, 96, 108 months. In control group remission was not achieved, overall mortality was 20%, overall 5-years survival was 70%. We conclude, that in treatment&refractory SLE high-dose immunosupression and HSCT it is effective to achieve disease control and it proves superior to the current standard of care.

Оценены отдаленные результаты высокодозной иммуносупрессивной терапии с аутотрансплантацией стволовых кроветворных клеток (ВДИСТ с АТСКК) у больных системной красной волчанкой (СКВ), рефрактерной кстандартной иммуносупрессивной терапии, в сравнении с дальнейшим продолжением стандартного лечения.Проведено исследование 15 больных, подвергшихся ВДИСТ с АТСКК в Центре трансплантации костного мозгаНИИ КИ с 1998 по 2008 гг. Группа контроля – 15 больных СКВ с неэффективной стандартной иммуносупрессивной терапией, которым продолжали стандартное лечение. Длительность наблюдения 45±10,4 мес. В результатеВДИСТ с АТСКК ремиссия констатирована у 6, снижение активности у 6 больных (по 40%), без эффекта –1 (7%), 2пациента умерли. Ранняя посттрансплантационная летальность – 13%. Годичная и пятилетняя выживаемость –80%, безрецидивная пятилетняя выживаемость – 20%. В отдаленном периоде рецидив выявлен у 7 больных (47%),умерли 3 пациента. В контрольной группе ремиссий не было, летальность составила 20%, общая пятилетняя выживаемость – 70%. Сделан вывод, что ВДИСТ с АТСКК эффективна в лечении тяжелой, резистентной к стандартной иммуносупрессивной терапии СКВ, и имеет преимущества перед продолжением стандартной терапии.

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.

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.

Systemic lupus erythematosus (SLE) is an immune-mediated disease that is responsive to suppression or modulation of the immune system. Patients with SLE who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide (Cy), represent a subset of patients at high risk of early death. We investigated the efficacy and toxicity of high-dose immunosuppression and autologous hematopoietic stem cell transplantation (SCT) to treat such patients. Six patients (all female, age 15-29 years) with severe refractory SLE were enrolled in the clinic of our institution from 1998 to 2003. All patients were seriously ill, with SLE disease activity indices (SLEDAI) of 6-30, including two cases with central nervous system lupus, one case with lung vasculitis, and three cases with nephritis and nephrotic syndrome. All patients were registered in the European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) database. Previous immunosuppression included pulse Cy intravenous, prednisolone (standard doses and pulse therapy), oral Cy and azathioprine, with little or no effect on disease progression. Autologous hemopoietic stem cells were collected from bone marrow (n = 4) or mobilized from peripheral blood with Cy and granulocyte colony-stimulating factor (G-CSF) (n = 2). Pre-transplant conditioning regimens included BEAM +/- ATG (n = 2), melphalan 140 mg/m2 + etoposid 1600 mg/m2 (n = 2) and Cy 200 mg/kg +/- ATG (n = 2). Median time to an absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L and platelet count greater than 50 x 10(9)/L was 13 and 15 days, respectively. Three patients died on days 11, 22 and 63 due to transplant-related complications. The follow-up is now 60 and six months for two patients (complete remission), and 42 months for one other patient (partial response). All patients had experienced multiple and severe episodes of infections pre-SCT and long-term history of corticosteroid therapy (3-14 years). We conclude that achievement of prolonged, corticosteroid-free remissions is a reality. Judicious selection of patients earlier in disease or in remission, but with a high risk of relapse or further progression, will diminish transplantation-related mortality.

Objective. To study relationship of anemic syndrome with inflammation activity measures in pts with rheumatoid arthritis (RA). Material and methods. 177 pts with RA fulfilled 1987 ACR criteria were included. 132 from them had anemia at the examination. Results were processed with complex of descriptive, structural and multivariate statistics. Results. Close relationship of RA clinical features with erythropoiesis disturbances clinically manifesting with anemia development was proved. Critical hemoglobin level (<113 g/1) was determined at which pathological processes in erythron leading to the development of anemia begin significantly influence severity of immunopathological rheumatoid process. Diapasons of disease activity measures were revealed associated with anemia presence or absence in pts with RA. Diagnostic value of studied measures diapasons for prognosis of anemia development in RA was determined. Conclusion. The results of the study allow developing criteria for prognosis of anemia appearance in RA pts with normal blood concentration of hemoglobin. Such method could help to reveal early disturbances of erythron and improve RA treatment schemes with erythropoiesis modulating drugs.

Objective. To study main parameters of immune status, disease activity measures and serum cytokines profile in rheumatoid arthritis (RA) pts with anemia. Material and methods. 20 pts with RA were examined before disease modifying drugs administration. They were divided into 2 groups: with anemia (9 pts) and without it (11 pts). Clinical and laboratory measures of disease activity immune status indices, and serum cytokine levels were compared in these groups. Correlation of hemoglobin level with RA activity measures and serum cytokine levels was analyzed. Results. Pts with anemia had higher clinical and laboratory activity measures (ESR, fibrinogen, CRP, fibrin degradation products and morning stiffness). Granulocytes and monocytes phagocytosis ability in this group was increased, monocytes activity index was significantly lower and interferon у level was significantly increased. Hemoglobin level showed an inverse correlation with RA activity measures and serum proinflammatory cytokine levels (interferon γ, TNF α and IL 6). Conclusion. Development of anemia in RA is usually accompanied by high disease activity. High level of interferon γ may be one of the causes of anemia development. Its neutralization may become a perspective direction of RA anticytokine therapy.

Anaemia of chronic disease (ACD) is a common feature of active rheumatoid arthritis. The aim of this study was to compare anaemic and non anaemic patients with rheumatoid arthritis. All patients were not treated with disease-modifying antirheumatic drugs. The groups of anaemic patients and patients without anaemia were compared by clinical and laboratory parameters as well as by profile of cytokines. This study shows that anaemic patients with rheumatoid arthritis had higher inflammatory activity and that circulating levels of interferon gamma and interleukin-12 are significantly increased as compared with patients without anaemia and that the increased levels may be implicated in the pathogenesis of anemia in patients with rheumatoid arthritis.