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Headaches are a common, but under-recognized symptom of rheumatic diseases. They can result from intracranial (inflammation, thrombosis, etc.) or extracranial pathology, such as irritation, or degeneration of anatomically related structures such as the eyes, neck, and sinuses. In addition, patients with rheumatologic disorders have the same tendencies as the general population to develop primary headaches. While the latter are benign in nature, the former type of headaches may signal disease manifestation, progression, or complication. Information on headache syndromes related to rheumatologic disorders as well as understanding of underlying disease processes and mechanisms is important. This will help to improve diagnostics and treatment of rheumatic diseases.

Background. Аnkylosing spondylitis (AS) is closely associated with inflammatory bowel disease (IBD). 5–10 % of patients with SpA eventually develop inflammatory bowel disease, with Crohn's disease being more common than ulcerative colitis. Colonoscopy is usually used to diagnose inflammatory bowel disease, but this procedure is invasive. FC is clinically used to detect IBD and correlates well with clinical, endoscopic, and histological indicators of disease activity in IBD.The aim. To evaluate the incidence of inflammatory bowel disease in patients with ankylosing spondylitis.Materials and methods. In the analysis were included 40 patients with ankylosing spondylitis, among them 26 (65.0 %) men, and 14 (35.0 %) women, the average age of patients was 41.2 ± 10.5, the duration of the disease was on average 13.0 ± 8.8 years. All patients were examined with ESR, CRP, esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the fecal calprotectin levels using the method of lateral immunochromatography with the BUHLMANN Quantum Blue rapid test. Standart range: 100–1,800 µg/g.Results. All patients had a high disease activity, the average BASDAI was 5.2 ± 1.7, the average ASDAS CRP 3.8 ± 1.1. 35 (87.5 %) patients had calprotectin level more than 100 µg/g, the remaining 5 (12.5 %) patients less than 100 µg/g. 12 (30.0 %) patients had the calprotectin level more than 1,800 µg/g, 23 (57.5 %) from 101 to 1800 µg/g. All patients with FC levels more than 100 µg/g showed an increase CRP level (mean 28.4 mg/l) and ESR (mean 36.3 mm/h). IBD were diagnosed in 9 (22.5 %) cases: 5 (12.5 %) patients with Crohn's disease and 4 (10 %) patients with ulcerative colitis, in the remaining (77.5 %) cases there was no intestinal pathology.Conclusion. The results showed high frequency of IBD in patients with AS. Patients with high fecal calprotectin levels (more than 100 μg/g) had high disease activity (AS). In most cases, inflammatory bowel disease were diagnosed in patients AS with fecal calprotectin levels more than 100 µg/g.

Aim: To evaluate the effectiveness, safety and anti-destructive effect of anti-B-cell therapy (rituximab) in various combinations (RTM-mono, RTM + DMARD, RTM + GK) in patients with rheumatoid arthritis in real clinical practice.Materials and methods: Clinical and radiological evaluation of 110 patients with rheumatoid arthritis who received rituximab therapy (RTM) as monotherapy (group 1), in combination with methotrexate (group 2), leflunomide (group 3), and group 4 with other basic anti-inflammatory drugs.Results: When assessing at 48 weeks of treatment with these regimens, the achievement of remission and a low degree of activity was observed in 22.36% of patients. An X-ray evaluation showed the absence of progression in the total score in 60.9%. When assessing progression in the monotherapy group, there was no progression in 76.92%, in the group of PTM + MT – in 54.29%, in the group of PTM + LEF – 65.0%, in the group of other DMARDs – 50% of patients. When assessing the clinical effect in the group receiving GK – remission and a low degree of activity – 19.67% of patients, in the group without GK – 21.05%. Assessing the radiological dynamics, it was shown that in the group not receiving GK – inhibition by the total score occurred in 54.55%, receiving – 61.54%.Conclusion: This work has demonstrated the high therapeutic efficacy of RTM in real clinical practice. There were no significant differences in the degree of progression depending on the concomitant therapy of DMARDs or GK. In the treatment of RTM, inhibition of articular destruction is possible even against the background of clinical deterioration.

A wide range of highly effective genetically engineered biological preparations introduced into clinical rheumatology in recent years causes a special interest in their safety.Purpose of the study. Evaluation of the safety of infliximab therapy in patients with rheumatoid arthritis.Materials and methods. The authors' own data, which analyzed the undesirable effects of infliximab in 135 patients with rheumatoid arthritis in actual clinical practice, are presented. A case report of the adverse reaction of combination therapy with leflunomide and infliximab is presented.Results and its discussion. The overall tolerability of infliximab was satisfactory. Adverse events were observed in 28.1 % of cases, including 19.1 % of patients (14.1 %) had serious side effects that required discontinuation of the drug.Findings. In most cases, infliximab is safe for use in actual clinical practice. Patients should be informed about the risks of undesirable effects and the need for a rheumatologist's examination before each infliximab administration before prescribing therapy.

This article presents the results of international studies of abatacept efficacy and safety and searching for possible predictors of a good response to the therapy with this drug in real clinical practice.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by pathological activation of the innate and acquired immune response, the formation of antinuclear antibodies (ANA), and dysregulation of cytokine production. Objective: to study the relationship of ANA and cytokine profiles in patients with SLE using multiplex immune analysis (MIA) of these biomarkers. We examined 94 patients with SLE (SLICC diagnosis criteria, 2012) and 28 healthy donors. Profiles of ANA and cytokines in blood serum were determined on the basis of suspension microarray technology xMAP. In SLE, antibodies to dsDNA (52.1 %), nucleosomes (54.3 %) and SS-A/Ro (37.2 %), less often to Sm (28.7 %), RibP (14, 9 %), RNP-70 (13.8 %) and SS-B/La (11.7 %). Disease activity (SLEDAI-2K) positively correlated with the concentration of antibodies to dsDNA (r = 0.6), nucleosomes (r = 0.7), Sm (r = 0.4) and RibP (r = 0.3) (p < 0.05). In the sera of patients with SLE, an increase in the levels of IL-4, -6, -8, -12, GM-CSF, MCP-1, MIP-1β, RANTES and a decrease in the content of IL-1β, IL-1ra, IL-2, IL-9, IL-10, eotaxin, G-CSF, IFN-γ, MIP-1α, TNF-α, FGF, PDGF-BB, VEGF compared to donors (p < 0.05). An increase in the concentration of IP-10 and MCP-1 was associated with high disease activity (r = 0.4; r = 0.3; p < 0.05), hyperproduction of antibodies to dsDNA (r = 0.3), nucleosomes (r = 0.5), Sm (r = 0.5), SS-B/La (r = 0.3), RibP (r = 0.4) (p < 0.05) and antibodies to Sm (r = 0.3), SS-B/La (r = 0.3), RibP (r = 0.3) (p < 0.05), respectively.Conclusion: the formation of ANA and high activity of SLE are associated with the overexpression of chemokines IP-10 and MCP-1 induced by IFN.

The purpose of these studies is to create an automated system for the drying process of agricultural raw materials. This system should be capable of providing biotechnological conditions for heating a single product to preserve especially valuable biological components in this product. Environmental problems of modern society determine the objective of functional nutrition of a person, as the basis of a healthy lifestyle. To solve this problem, it is necessary to obtain products of high nutritional value, with a maximum content of active substances. Each plant product contains not only vitamins and minerals, but also elements that determine its special value. During storage, these components are lost due to biological characteristics and storage conditions. To preserve them for a long period and create a product of high nutritional value, certain conservation methods must be used. Such methods include drying. Products dried in a special way are able to maintain up to 95% of their valuable indicators. An analysis of modern drying methods for plant raw materials showed that the pulse infrared-convection method more closely meets the requirements of biotechnological heating conditions and is therefore suitable for obtaining products of high nutritional value. This method has a sterilizing effect, which allows to increase the shelf life of finished products. The creation of an automated control system for pulse infrared - convection radiation made it possible to obtain products of high nutritional value for long-term storage.

A promising trend in the diagnosis of systemic autoimmune diseases is the multiplex immune assay (MIA) of autoantibodies and other laboratory biomarkers using microchips. The aim of the work was to study the diagnostic and prognostic significance of MIA antinuclear antibody (ANA) profiles in systemic lupus erythematosus (SLE). 94 patients with SLE, 70 patients with other rheumatic diseases and 30 healthy donors were examined. ANA (antibodies to doublestranded - dsDNA, Sm, SS-A/Ro, SS-B/La antigens, nucleosomes, ribosomal protein P-RibP and ribonucleoprotein - RNP-70) were determined in the serum by MIA using the xMAP technology. In MIA, antibodies to dsDNA, Sm and RibP have a high diagnostic specificity (Sp) (95.0-99.0%) and a likelihood ratio of positive results (LR+) (9.67-15.0), i.e. are the most "useful" diagnostic tests, and antibodies to RNP-70, SS-A/Ro and nucleosomes are classified as "useful" tests for the diagnosis of SLE (Sp: 84.0-95.0%, LR+2.0). Determination of profiles from 3 or more antigen-specific ANA by MIA increases the Sp method to 98.0-100%, and the LR+ - to the maximum values. Profiles from 7 subpopulations of ANA (antibodies to dsDNA, Sm, RibP, SS-A/Ro,SS-B/La, nucleosomes and RNP-70, 57.9%, 71.9%, 82.5%, 61.4 %, 84.2%, 50.9%, 84.2%) were found in the chronic variant of SLE. In the acute course of the disease, 4 subpopulations of ANA are simultaneously detected (antibodies to dsDNA, Sm, SS-A/Ro and nucleosomes, 77.3%, 45.5%, 40.9% and 72.7%); in subacute course there are 2 subpopulations of ANA (antibodies to dsDNA and nucleosomes, 53.3% and 46.7%). The activity index of SLEDAI-2K positively correlates with the concentration of antibodies to dsDNA (r = 0.55, p0.05), nucleosomes (r = 0.65, p0.05), RibP (r = 0.32; p0.05) and Sm (r = 0.36, p0.05) in the blood. There was no reliable relationship between the production of varieties of ANA and the index of organ damage. Mucocutaneous disorders, lupus-nephritis and neurolupus were most often associated with the detection of antibodies to dsDNA (53.2-64.0%), nucleosomes (55.3-66.0%), SS-A/Ro (38.0-40.4%) and Sm (27.8-36.2%). MIA of ANA profiles is an important tool for implementing a personalized approach to diagnosis, evaluation of activity, course and clinical and immunologic subtypes of SLE.

In the review, topical aspects of the study of antinuclear antibodies (ANA) in systemic lupus erythematosus (SLE) are considered. ANA is the main serological marker of SLE. In the sera of patients with SLE, antibodies to DNA, histones, nucleosomes, extractable nuclear antigens (Sm, U1 ribonucleoprotein, Ro / SSA, La / SSB, ribosomal protein P), nucleolar antigens and other cellular structures are detected. The ANA study using indirect immunofluorescence on HEp-2 cells (IIF-HEp-2) is recommended as a standard screening test for the diagnosis of SLE. The use of automated systems for the interpretation of cellular fluorescent tests contributes to the standardization and improvement of the reproducibility of the IIF. A new international nomenclature of types of nuclear, nucleolar (nucleolar), cytoplasmic and mitotic luminescence of ANA in IIF-HEp-2, including 28 variants of anticell ("Anti-cell" - AC) patterns was developed. In the practice of clinical diagnostic laboratories, high-performance automated methods for the determination of ANA based on ELISA, immunoblot, fluorescent, chemiluminescent and multiplex immunoassay are widely used. New mono- and multiplex methods of solid-phase analysis are expediently used as confirmatory reflex tests for the detection of varieties of antigen-specific ANA in patients with SLE with positive results of IIF-HEp-2. Identification of ANA profiles using multiplex technologies is a useful tool for implementing a personalized approach to diagnosis, evaluation of activity, prognosis, clinical and immunological subtypes, and the effectiveness of SLE therapy. The need for an ANA study not only to confirm the diagnosis of SLE, but also to identify the disease in the early and preclinical stages with the intention to prevent the development of the pathological process is discussed. Detection of monospecific anti-DFS70 antibodies allows to exclude the diagnosis of SLE inANA IIF-HEp-2 positive subjects. Presented is a modern algorithm for testing ANA with SLE.

The clinical analysis of the results of genetically engineered biological therapy identifies a number of patterns of the mechanism of action of this therapy and the pathogenetic features of rheumatic diseases. The results of using genetically engineered biological agents (GEBA) having different mechanisms of action allow one to identify categories of rheumatoid arthritis patients with different pathogenetic features. Various cytokines can play a major pathogenic role in a clinically similar inflammatory process. The therapeutic effect of tumor necrosis factor-α (TNF-α) inhibitors exhibits the predominance of their nonspecific anti-inflammatory activity over the immunosuppressive one. Contrary to the previous ideas of cytokine hierarchy, TNF-α neutralization does not block the effects of interleukin 6 (IL-6). Anti-B-cell therapy is most effective in patients with significant autoimmune disorders; a contrary pattern is observed when TNF-α inhibitors are used. TNF-α is very important in the development of an inflammatory process in ankylosing spondylitis (AS) while the role of IL6 is insignificant. Autoimmune disorders in AS are not marked; whereby predominantly immunotropic GEBAs (rituximab and abatacept) are ineffective in this disease. The blocking of a biological reaction to inflammation cannot coincide with the suppression of the inflammatory process proper.

Objective: to estimate the contribution of arthrosonography to the diagnosis of metatarsophalangeal joint (MTPJ) injury and to reveal predictors for functional impairments in patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 50 patients with the RA diagnosis meeting to the American College of Rheumatology 1987 criteria. According to disease duration, the patients were divided into two groups: 1) 9 patients with an early RA history of less than 2 years (ERA); 2) 41 patients with a RA history of over 2 years (LRA). All the patients underwent clinical joint evaluation, laboratory and instrumental examination, including joint X-ray and ultrasonography (USG). Results. An inflammatory process in the foot joints is significantly more frequently detected on ultrasound than clinically (p < 0.0001). The detection rate of erosions, as evidenced by USG, was significantly higher than that by X-ray, in ERA in particular (p = 0.01). Comparison analysis of patients with low and high HAQ scores showed the relationship between functional status, age, pain degree, and inflammatory process in the fifth MTPJ, as shown by USG. There were no associations with disease duration, traditional clinical and laboratory parameters of RA activity, and erosive changes in the feet. Conclusion. Joint USG in daily clinical practice makes it possible to objectively evaluate pathological changes in the feet and the probability of work disability due to RA.

Analysis of the literature on anti-cytokine therapy demonstrates the effectiveness of this therapy, compared with conventional glucocorticosteroid and immunosuppressive therapy. Drugs with anti-cytokine mechanism of action can be used in Ophthalmology, as inhibitors of angiogenesis in neovascularization and anti-inflammatory therapy in uveitis. Route of administration of TNF inhibitors are intravenous and subcutaneous. They can be used as monotherapy or with the glucocorticosteroid and immunosuppressive therapy. From the literature it is obvious, that the effect of the use of this group of drugs are dose-dependent and they can be positive (anti-angiogenic and anti-inflammatory) and negative — toxic. In a comparative aspects, studies show, that Infliximab has more pronounced anti-inflammatory effect, but at the same time, use of Infliximab is more often with side effects and complications. According to different authors, doses that cause side effects, are not comparable. It seems that, localization of inflammatory process plays a role in the vascular tract of the eye (front, rear), etiologic factor, causing the inflammation and, of course, the intensity of cytokine responses. Therefore, the question, the efficacy and tolerability of anti-cytokine drugs are dose-dependent, and whether, there are other factors that influence on the success of treatment -remains open. To answer these questions is required a detailed study, investigating the influence of this group of drugs on the eye tissues, pathological angiogenesis processes depending on the drug, the dose and the conditions of its application, and testing of optimal dosage of drugs to avoid side effects.

The study of infliximab began (INF) in Russia in 2001. It was the first genetically engineered biological agent (GEBA) registered in our country to treat patients with rheumatoid arthritis (RA). With the advent of infliximab, a Russian biological rheumatoid arthritis therapy registry started its work. In October 2005, it was set up on the basis of GEBA centers founded in the leading rheumatology clinics of Russia. Objective: to generalize the Russian experience in using INF (its efficacy, tolerance, and side effects) in patients with RA in real clinical practice within the framework of a multicenter observational study. Subjects and methods. The register included patients with a valid diagnosis of RA in whom INF treatment was first started. The main indication for this was previous basic therapy failure. This investigation analyzed 396 patients receiving INF therapy. Prior to INF administration, all the patients were examined to identify whether they had possible latent tuberculosis, by applying chest X-ray study and Mantoux test. The European League Against Rheumatism criteria were used to evaluate the efficiency of INF therapy. The relationship between the therapeutic effects of the drug and its cumulative dose was specially used. The trend in X-ray progression was estimated using the Sharp method modified by van der Heijde. INF was given in a dose of 3 mg/kg by the classical regimen: at 0, 2, and 6 weeks, then every 8 weeks. The main assessment periods were at 22 and 46—54 weeks. Results. Analysis of the data of real clinical practice in Russia demonstrates that the use of INF in RA patients with the inadequate effect of traditional disease-modifying antirheumatic drugs (DMARDs) is able to cause a rapid and pronounced reduction in disease activity. There is significant evidence that the IFN-treated patients with RA had also suppressed bone destruction. INF treatment for early RA gives rise to remissions more frequently in the early stage of therapy than that for extensive-stage disease. INF was shown to have a clear dose-dependent effect: in the patients receiving more than 4 infusions of the drug, bone destruction was more noticeably suppressed than in those having its fewer infusions. In most cases, suppressed destruction was accompanied by clinical improvement. A significant therapeutic effect was seen when both an annual course of INF and average (5—7 infusions per year) doses of the drug were used. The results of the analysis suggest that the probable efficiency of INF therapy increases in RF-negative patients with lower baseline RA activity and fewer HAQ scores. INF was quiet satisfactorily tolerated and caused no unusual side effects. Conclusion. The Russian experience in using INF strongly suggests that it is effective in real practice in severe RA resistant to therapy with traditional DMARDs.

Objective: to evaluate the efficiency of two tocilizumab (TCZ) infusions in patients with rheumatoid arthritis (RA). Subjects and methods. The study enrolled 43 middle-aged patients with RA, mainly female ones (male/female ratio 10:33) with a RA history of 5.6±4.74 years, who were seropositive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies and had high disease activity scores (DAS 28 - 6.3) prior to TCZ treatment and received disease-modifying anti-inflammatory agents, including methotrexate and glucocorticoids without providing any therapeutic effect. Therapy with TCZ was performed by the standard regimen; the dose of the drug was 8 mg/kg per infusion. The therapeutic effectiveness was evaluated 4 weeks after each infusion and by the time course of changes in DAS 28, its individual components, and health assessment questionnaire scores. Results. After the first TCZ infusion, the patients with RA were found to have significant positive changes in the major clinical and laboratory parameters of disease activity (p < 0.0001 in all cases) that progressed after the second TCZ infusion. There were reductions in DAS 28 to 4.1 and 3.1 after each infusion and in the number of patients with high disease activity and an increase in that of patients with low/moderate one. At the same time, more than 20% of the patients developed remission after the second infusion. A good therapeutic effect was noted in 14 and 51% of the patients after the first and second infusions, respectively. Conclusion. TCZ exerts a rapid statistically significant positive effect on the major clinical and laboratory parameters of RA activity.

The paper analyzes the efficiency and tolerability of a combination of rituximab (RTM) and leflunomide (LEF) for the treatment of rheumatoid arthritis (RA) versus the conventional combination of RTM and methotrexate (MT). The results of 24-week therapy were assessed in the RA patients included into the Russian Biological Therapy Register. A good effect of therapy was achieved in 31.8% of the patients who had received RTM+LEF (p = 0.1). The development of clinical remissions in RA was observed at a practically equal frequency of 13.6 and 11.7%, respectively. The doses of glucocorticoids and nonsteroidal anti-inflammatory drugs used in concurrent anti-inflammatory therapy could be substantially reduced in both groups. In both groups, the rate of side effects was very equal: 21.7% for the RTM+LEF group and 25.7% for the RTM+MT group. Thus, the combination therapy of RTM and LEF in real clinical practice is not considerably different from the most commonly used combination of RMT and MT in efficiency and tolerability and may be successfully used if there are any contraindications to the use of MT.

Objective. To evaluate the functional state of rheumatoid arthritis (RA) patients receiving Infliximab therapy (IF) in real clinical practice and its efficiency. Subjects and methods. The analysis covered 225 patients receiving IF therapy, the follow-up duration in whom was 54 weeks. Disease activity was estimated by the DAS 28 index; functional status was assessed according to the Health Assessment Questionnaire (HAQ). The authors made an analysis of a Per-Protocol (PP) population (n = 154) at 54 weeks of treatment and an analysis that could consider the results of treatment (by the ACR and EULAR criteria) in patients who had been withdrawn before the control time - a LOCF (Last Observation Carried Forward analysis) population. Results. The mean age of the patients was 47.6±11.4 years; the duration of the disease was 7.8±6.4 years; DAS 28 activity scores were 6.6±1.1; the majority of patients had significant functional impairments (HAQ scores of 2.0±0.7), 86.7% of the patients had extraarticular manifestations; 79.6% were found to have rheumatoid factor (RF); the patients received an average of > 2 disease-modifying antirheumatic drugs (DMARDs). After 2 week-therapy, there was a reduction in RA activity by DAS 28 index in both the PP (from 6.7±1.1 to 4.0±1.4) and LOCF (6.6±1.1 and 4.2±1.4; p < 106) populations. Drug-induced remission (DAS 28 < 2.6) at 54 weeks was observed in 16.9 and 15.1% of the patients, respectively. Functional improvement was noted in the PP population: HAQ decreased from 2.0±0.7 to 1.7±0.7 scores by week 2; its reduction continued until week 14 (p < 0.05), by remaining stable later on. HAQ dropped from 2.0±0.7 to 1.2±0.7 scores in the LOCF population. At 54 weeks, normal population values of functional activity were achieved in 16.4%. Log regression analysis in the LOCF population indicated that the previous use of DMARDs and a short history of the disease were predictors of an ACR70 response to IF therapy [OR=1.61 (1.13-2.30), p = 0.008 and OR = 0.91 (0.84-0.98), p = 0.018, respectively]. RF seronegativity was a predictor for achievement of low RA activity [OR = 0.44 (0.23-0.84)]. The previous use of glucocorticoids failed to increase the probability of a good response to IF therapy and achievement of clinical remission [OR = 0.26 (0.11-0.60), p = 0.001]. Conclusion. Therapy with IF in combination with methotrexate or other DMARDs reduces RA activity and improves the functional capacities of patients with RA in real clinical practice.

Endothelial dysfunction plays a key role in the pathogenesis of atherosclerosis. An increased cardiovascular risk in patients with rheumatoid arthritis (RA) suggests that inflammation is of importance for the occurrence and progression of atherosclerosis. Rituximab (RTM, monoclonal antibodies to CD20-positive B lymphocytes) is used to treat patients with active RA. Objective. To evaluate the effect of RTM on endothelial function in patients with active RA. Subjects and methods. The study enrolled 20patients with active RA (DAS 28 >5.0); their mean age was 50 (range 41.5 to 63) years; mean disease duration was 95.7 (range 24 to 144) months. Intravenous RTM was used (as a course of 2 infusions in a dose of 1000 mg at a 2-week interval) in all the patients. Brachial artery flow-dependent vasodilation (FDVD) that was carried out in all the patients at screening (before the first infusion) and also at 2, 8, 16, and 24 weeks after the second infusion was employed to evaluate endothelial function. Results. Before RTM therapy, the study group of patients showed no statistically significant deviations of FDVD values from those in the gender- and age-matched control group. FDVD correlated with age (r=-0.44; p=0.049), disease duration (r = 0.6; p=0.017), cholesterol level (r=0.48; p=0.045), common carotid artery intima-media thickness (r=0.52; p=0.023), and cardiovascular risk factors (r=0.51; p=0.027). No statistically significant differences were found in the baseline value of FDVD and those observed after a course of RTM therapy and at weeks 8, 16, 24 (12.8±5.7, 11.3±5.2, 14.3±7.1, and 12.5±5.2%, respectively). All the patients were divided into 2 groups according to their response (an increase or a reduction in FDVD over time). Group 1 patients (n=10) demonstrated a significant increase in this index from 10.74±5.75 (at screening) to 14.17±5.13% (at week 24) (p

The peculiarities of detection using the location method of single-line-to-ground faults in the electricity transmission lines (ETLs) with 6–35 kV of tree topology and linear structures of 110 kV and higher have been studied. Ways of recognizing reflectograms if there is a fault in the ETL are presented. The investigations were carried out in laboratory settings using ETL models and under real conditions on working ETLs.

Objective. To study lymphocytes phenotype in rheumatoid arthritis (RA) and its changes during methotrexate (MT) therapy. Methods. 24 RA pts with high clinical and laboratory activity of the disease and 18 healthy donors (control group) were included. All patients received MT 7,5-15 mg/week. They were followed up for 6 months. Expression of CD3, CD5, CD7, CD8, CD16, CD18, CD19, CD20, CD25, CD26, CD50, CD54, HLA DR, CD95 on peripheral blood lymphocytes was assessed before and after treatment by immunofluorescence method. Results. There was decreased expression of CD8, CD18, and CD50 in RA patients vs control. MT treatment resulted in reduction of CD 50 and CD 26 expression on lymphocytes. Conclusion. Peripheral blood in RA is characterized by decrease of CD8+ lymphocyte percent. Reduction of CD 18 and CD50 adhesion molecules expression may be connected with migration of appropriate effector cells bearing these molecules on there surface into inflamed synovial membrane. Treatment with MT decreased expression of some adhesion molecules. Decrease of CD 26 lymphocytes activation marker expression is one of the mechanisms of MT antirheumatic action.

To analyse the data on infliximab administration (efficacy, tolerance, toxicity) in patients with rheumatoid arthritis (RA) in Russia by clinical evidence provided by the multicenter observation trial.The register included 297 patients with a documented diagnosis of RA who had for the first time treated with infliximab. The efficacy of the drug was evaluated by EULAR criteria based on the dynamics of DAS28 index.The results of infliximab treatment show good response of RA patients to standard courses of infliximab. A good/satisfactory effect by EULAR criteria was achieved in 80% patients to week 22 of therapy and in 85% to week 46. After 6-month (22 week) infliximab treatment a good effect was achieved in 15.7% patients, satisfactory--in 64.7%; 19.6% patients did not respond. Remission (DAS282.6 units) was achieved in 7% patients. Infliximab tolerance was satisfactory. Non-severe infusion reactions were most frequent unwanted effects. To treatment week 22, ten patients developed serious side effects causing the drug discontinuation.The results of the Russian register confirm a high therapeutic potential and satisfactory tolerance of infliximab observed in real rheumatological practice of the treatment of severe RA. These results agree with those of European registers of infliximab.

State-of-the-art state of biological therapy of rheumatoid arthritis is analyzed. Its pathogenetic reasons are represented. Main direction of this therapy, such as blocking of tumor necrosis factor alpha and interleukin-1, inhibition of interaction between T-lymphocytes and antigen representing cells, elimination of B-cells, are considered. Special attention is devoted to new perspective methods of biological treatment, among which the special interest has first applied in RAMS Institute of Rheumatology method of interferon-gamma neutralization. Combination of anti-inflammatory, immune depressive and significant destructive actions leads to significant curative effect of biological therapy, exceeding results of the use of classic basic drugs including methotrexate. The achievement of clinical remission of rheumatoid arthritis first became the real aim of its treatment, and methods of biological therapy in contrast to former "disease-modifying" remedies could be considered as real "disease-controlling" drugs. Biological therapy revolutionized modern rheumatology and in the nearest years would demonstrated new fundamental accesses.

The development and introduction of the anti-cytokine therapy applicable to rheumatoid arthritis (RA) is a most significant achievement in RA therapy. A high degree of purpose-orientation and selectivity of the mentioned method ensuring a high therapeutic effect and providing, simultaneously, for defining a number of important chains in RA pathogenesis is an essential advantage of the discussed approach. The clinical use of neutralization of key cytokines TNF-alpha, IL-1 and IF-gamma is a serious progress within this trend. Possibilities of developing new directions of the cytokines therapy are preconditioned, to a great extent, by the role of new, including little-studied cytokines, in the evolution of immune inflammation. A search for more simple low-molecular inhibitors of cytokines, which do not cause any tolerance-related problems, is another important trend. Hopefully, a further study of anti-cytokines and of their application in combination with other antirheumatic drugs will improve the general treatment results and outline new opportunities in antirheumatic therapy.

To study effectiveness and tolerance of monoclonal antibodies to tumor necrosis factor (the drug remicade) in patients with rheumatoid arthritis (RA).Remicade treatment results are considered for 25 RA patients receiving methotrexate the activity of which was inadequate for these patients. Remicade was infused intravenously in a dose 200 mg 4 times for 22 weeks.Remicade produced positive clinical and laboratory effects as early as the first infusion. The response was observed during 22 weeks of the treatment in 17 of 25 patients. Remicade tolerance was good. One patient failed the treatment because of development of collapse.Pilot results of remicade trial point to its high therapeutic potential and perspectives in rheumatology.

Objective evaluation of the effectiveness and tolerance of antibodies to interferon-gamma (TNF-gamma) vs those to tumor necrosis factor-alpha (TNF-a) and placebo in patients with rheumatoid arthritis (RA).A double blind randomised controlled trial of effectiveness and tolerance of anticytokine antibodies was conducted in 30 patients with active RA. The drugs were given i.m. for 5 consecutive days. The results were assessed on day 7 and 28.Antibodies to both cytokines produced a marked therapeutic effect in RA, much greater than placebo effect. Improvement by day 7 was achieved in 9, 7 and 2 patients on anti-TNF-a, anti-INF-g and placebo, respectively. By day 28 in 8, 8 and 0 patients, respectively. Tolerance of anticytokines was good. Significant differences between the results of treatment with anti-INF-g and anti-TNF-a were not found.Administration of antibodies to INF-a proved ineffective and well tolerated method in the treatment of severe RA resistant for a number of standard basic drugs. Anti-IFN-a holds great promise when used in combination with classic antirheumatoid drugs, primarily with methotrexate.

Investigation of efficacy of antibodies ot interferons in rheumatoid arthritis (RA) versus relevant efficacy of the tumor necrosis factor (TNF), comparison of the above cytokines in monotherapy and combined treatment.An open controlled randomized trial of clinical benefit and tolerance of anticytokine antibodies was performed in a group of RA patients at stage II, III and IV (1, 20 and 4 patients, respectively). The activity degree II and III was in 10 and 15 patients, respectively. All the patients had articular functional insufficiency of the second degree. 21 patients failed previous therapy with basic drugs including immunodepressants.The anticytokine antibodies proved to be highly effective in RA. Positive changes in teh disease activity were achieved early after the end of the 5-day course in 88% of patients. The most definite immediate therapeutic effect was noted in usage of TNF antibodies both in monotherapy and in combination with other anticytokines. Long-term effect was the best in patients given antibodies to interferon gamma. Interferon-alpha antibodies produced weaker effect. The combined treatment had no advantages over the monotherapy.A significant therapeutic effect of antibodies to interferon-gamma is indicative of an important role of this cytokine in RA pathogenesis. Anticytokine antibodies are promising as a component of combined therapy of patients with resistant RA.

Objective: to study the time course of changes in laboratory biomarkers in patients with rheumatoid arthritis (RA) 2, 4, and 8 weeks after the initiation of tocilizumab (TCZ) therapy. Subjects and methods. Forty-two RA patients receiving two intravenous infusions of TCZ (8 mg/kg each) at a 4-week interval during steady-state therapy with disease-modifying anti-inflammatory agents and glucocorticoids were examined. At week 8 of therapy, there were good and moderate effects in 21 and 20 patients, respectively, according to the EULAR criteria; no effect was found in 1 patient. Erythrocyte sedimentation rate (ESR) was determined by the Westergren method; the serum levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) were measured by the nephelometric method; anti-cyclic citrullinated peptide antibodies (ACCPA) were estimated by an ummunoluminescence assay. Serum interleukin (IL) 6 concentrations were measured by multiplex analysis; IgA RF, anti-modified citrullinated vimentin (anti-MCV) antibodies, and soluble IL-6 receptors (sIL-6R) were determined by enzyme immunoassay. Results. The patients who showed a response to TCZ therapy had the basal values: Me (RI 25-75 percentile) was 42 (30-70) mm/hr for ESR, 35.2 (19.2-62.7) mg/l for CRP, 263.0 (95.3-663.0) IU/ml for IgM RF, 347.0 (131.2-789.0) IU/ml for IgA RF, 378.8 (85.8-500.0) IU/ml for ACCPA, 778.6 (190.7-2393.1) IU/ml for anti-MCV, 182.2 (106.1-462.3) pg/ml for IL-6, and 267.2 (212.5-310.0) ng/ml for sIL-6R. At TCZ therapy week 2, there were reductions in ESR [12 (6-18) mm/hr], CRP [0.5(0.3-0.9) mg/l], IgM RF [174.0 (40.8-513.0) IU/ml], and IgA RF [227.2 (62.1-570.8) IU/ml]; at week 4, anti-MCV titers were 313.5 (79.9-960.3) IU/ml, which remained until week 8 (p < 0.01). IL-6 concentrations were increased at week 2 and reduced at week 8; these were 418.4 (287.0-678.3) and 103.4 (39.1-208.5) pg/ml, respectively (p < 0.01). The elevated sIL-6R level of 1250.0 (1250.0-1475.0) ng/ml was recorded at weeks 2 to 8 of TCZ use (p < 0.01). Conclusion. The interim analysis of the efficacy of two TCZ infusions 2, 4, and 8 weeks after the initiation of the therapy suggests that TCZ is able to induce steady-state positive changes in immune-inflammatory markers very rapidly in patients with RA

Ревматоидный артрит (РА) – аутоиммунное ревматическое заболевание неизвестной этиологии, характеризующееся хроническим эрозивным артритом (синовитом) и нередким системным воспа- лительным поражением внутренних органов. Его распространенность в популяции колеблется от 0.5% до 1.0% [1]. Социальное и медицинское значение РА определяется значительной инвалидностью и сокращением продолжительности жизни пациентов [2-4]. До недавнего времени патогенетические механизмы развития РА рассматривались главным образом с точки зрения дефектов Т-клеточной иммунорегуляции [5-7]. Однако данные экспериментальных исследований, свидетельствующие о фундаментальной роли В-лимфоцитов в нарушении иммунного ответа при РА [7-11], послужили стимулом для изучения этих клеток в качестве объекта антиревматической терапии. В результате в арсенал ревматологов вошел анти-В-клеточный биологический препарат ритуксимаб, или Мабтерa [12-16]. Ритуксимаб (мабтера) представляет собой генноинженерное химерное моноклональное антитело, состоящее из человеческого и мышиного белка. Оно направлено против антигена CD20, находящегося на поверхности пре В-клеток и зрелых В-клеток, но не на развивающихся из них плазматических клетках, которые являются продуцентами антител. Поэтому применение ритуксимаба приводит к резкому сокращению на длительный срок популяции зрелых В-клеток; количество же вырабатывающих антитела плазматических клеток существенно не изменяется. Соответственно этому уровень циркулирующих антител не обнаруживает значительного снижения. CD20 отсутствует также на стволовых, дендритных и прo-В клетках, в связи с чем ритуксимаб не влияет на их функцию и количество. Период полувыведения препарата из сыворотки составляет около 20 дней [17].

Во всем мире продолжается разработка эффективных средств для диагностики и лечения ревматических заболеваний. В последнее десятилетие сделано большое количество открытий, созданы принципиально новые технологии, основанные на использовании достижений молекулярной биологии, которые позволяют значительно улучшить качество жизни (КЖ) больных тяжелыми воспалительными заболеваниями суставов.Все большее значение приобретает оценка экономической эффективности терапии больных ревматоидным артритом (РА). Это обусловлено быстрыми темпами роста стоимости лечения, особенно вследствие все более широкого применения новых генно-инженерных биологических препаратов, при выборе которых приходится учитывать не только их клиническую эффективность, но и стоимость, а также тенденцией к общему удорожанию медицинских услуг. Ни одно государство не располагает достаточными средствами для того, чтобы полностью покрыть потребности национального здравоохранения, а для рационального их распределения необходимо проведение тщательного экономического анализа [1].

Summary Aljlutup is an effective and well tolerable drug which not only decreases pains and other clinical manifestations of secondary synovitis but also has positive effect on the structure of articular cartilage.