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.

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.

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.