DNA-abzymes enzymes in autoimmune diseases in clinic and experiment T.E. Naumova, O.M. Durova, A.G. Gabibov, Z.S. Alekberova, S. V. Suchkov DNA-hydrolyzing autoantibodies (AAB) or DNA-abzymes can be found in autoimmune diseases in clinic and experiment. Technology of serum express screening for presence of DNA abzymes is described. Comparative study of DNA-hydrolising activity in patients with different forms of systemic and organ-specific autoimmune diseases was performed. Blood of clinically healthy donors was usually free of IgG DNA-abzymes. DNA-abzymes were most often revealed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) less often in patients with organ-specific forms of autoimmune disturbances. The results of the study confirm the hypothesis of autoimmune origin of IgG DNA abzymes and demonstrate the possibility to use them in clinical practice for monitoring to disease activity in SLE and RA.

Objective. Pts with chronic clonal proliferation of large granular lymphocytes (LGL leukemia) often have neutropenia, splenomegaly, and rheumatoid arthritis (RA), thereby resembling the manifestations observed in pts with Felty’s syndrome. The present study sought to indicate that pts with these disorders represent two distinct subsets. We compare clinical, hematological, immunophenotiping and immunogenetic features in Felty’s syndrome pts with and without the LGL leukemia. Material and methods 10 pts with T-LGL leukemia were studied. Surface phenotype was estimated using monoclonal antibodies CD8-PE and CD3-FITC/CD16-PE (two-color) (Caltag, USA) by the flow cytometric analysis (Partec, Daco). Analysis of TCR gene rearrangement was performed by using PCR-LIS SSCP (low ionic strength single strand conformational polymorphism). Comparison with Felty s syndrome and RA pts based on the review of literature. Results. LGL leukemia is a distinct clinicopathologic entity often associated with RA. LGL leukemia pts with RA showed the same immunogenetis associations seen in RA/Felty’s syndrome, while LGL leukemia pts without arthritis did not. Conclusion. Hematologic, immunophenotyping and molecular genetic analysis are very important and highly representative tools in differential diagnosis of neutropenia in RA, and propose that Felty’s syndrome and LGL leukemia represent different variants of broader syndrome comprising RA, neutropenia, LGL expansions, and splenomegaly.

Objective. To assess expression of P-glycoprotein (Pgp) on peripheral blood (PB) lymphocytes and its changes during therapy in pts with rheumatoid arthritis (RA). Methods. 51 RA pts and 11 healthy donors (control group) were examined. 35 pts were followed up. 20 of them were treated with methotrexate (MT) and 15 with glucocorticosteroid (GCS) pulse therapy (PT). Pgp expression was examined with flow cytofluorometry with monoclonal antibodies (UIC2 PE, Immunotech). Results. Pgp expression on PB lymphocytes in RA was significantly more prominent (29,3 29,9 %) than in control group (2,5 2,0 %), P<0,01. Pgp expression did not depend on pts age and sex, duration and stage of the disease, presence or absence history of disease modifying drugs therapy. PT with GCS but not MT significantly decreased Pgp expression (from 57,2±27,0 % to 28,8135,2 %, r<0,05). Conclusion. RA patients have increased Pgp expression, which is probably biologically sensible but clinically unfavourable response of immunocompetent cells to durable application of such foreign substances as medications. PT with GCS decrease Pgp expression on lymphocytes while treatment with MT does not change it.

Objective. To study (32 glycoprotein 1 contribution to frequency of aCL in pts with autoimmune and some infectious diseases. Methods. Antibodies to different phospholipids were tested by immune-enzyme method (IEM) in serum of 92 pts: 20 of them had systemic lupus erythematosus (SLE), 15 Sjogren’s disease (SD), 20 rheumatoid arthritis (RA), 20 syphilis and 17 Lyme disease (LD). Pts with syphilis and LD did not have clinical signs of autoimmune disease. Stimulation of aCL test in IEM was performed after previous cardiolipin incubation on microtitrated plates with electrophoretic pure p2 glycoprotein 1. Results. aCL were mostly revealed in serum of patients with SLE and syphilis, less often in SD. In aCL- positive serums antibodies to some other phospholipids were found. Mean values of stimulating aCL test in IEM after previous incubation with pure |32-glycoprotein 1 in autoimmune diseases were higher than in infection. aCL division into cofactor «dependent» and «independent» or autoimmune and infectious types seems to be not final.

Objective. To assess frequency of antikeratin antibodies (AKA) in rheumatoid arthritis (RA). Methods. AKA were measured by indirect immunofluorescence and Western blott in serum of 58 RA patients (43 f and 15 m) and 30 healthy donors. Results. AKA were found in 76% of RA patients not depending of duration of the disease and age of patients. AKA specificity for RA was 96%. Conclusion. Role of AKA in the development of RA and their diagnostic significance need further examination.

Objective. To determine structural origin of joint pain in hypermobility syndrome (HS) by sonographic scanning. Material and. 48 women aged 16 to 25 years were examined. 21 HS patients of group 1 had knee pain (12 bilateral and 9 unilateral, 33 painful joints), group II consisted of 17 women with HS without knee pain. 10 healthy women were included in control group. Degree of hypermobility was assessed according to Beighton score. Sonographic examination was performed with 5-7,5 MHz linear and convex probes. Thickness of synovial tissue and femur condyles cartilage, presence of synovial fluid, state of menisci, collateral ligaments, m. semimembranosus tendon was estimated. Results. Sonographic changes (mainly collateral ligaments edema and tendinitis of m. semimembranosus tendon) were found in 30 of 33 painful joints of group 1, 16 of 34 joints of group II and only 1 of 20 joints of control group. Frequency of tissue changes adjacent to knee joint differed significantly between groups 1 and II (p=0,001), I and III (p=0,000), 2 and 3 (p=0,01). Conclusion. In most cases knee joint pain in HS is accompanied by sonographic signs of soft tissue damage - mainly collateral ligaments edema and tendinitis of m. semimembranosus tendon. These changes in HS may be asymptomatic.

Objective. To assess safety of nimesulid in rheumatic pts with history of ulcer or multiple erosions (ME) of stomach and/or duodenal mucosa. Methods. 42 pts with rheumatic diseases aged 22-73 years were included. AH had gastric or duodenal ulcers or ME (n>10) connected with NSAID treatment and confirmed by endoscopy no more than 6 months before the beginning of the study. Pts were included after healing of ulcers and erosions. The pts were randomized to receive Nimesulid 200 mg/day (group 1) or Diclofenac suppositoria 100 mg/day + ranitidine 150 mg/day (group 2). Esophagogastroduodenoscopy was performed before and 12 weeks after the beginning of treatment. Results. Relapse of stomach ulcer was observed in I pts of group 1 (5,6%). Relapse of NSAID-induced ulcers and ME was noted in 6 pts of group 2 (33,3%): in 4 cases stomach ulcers, in 1 case stomach ME, in 1 case duodenal ulcer (p=0,0424). Presence of gastralgias and dyspepsia was noted in 36,8% pts of group 1 and in 20% pts of group 2 (p=0,0539). In 1 pts of group 2 gastralgias were the reason for premature endoscopy. Conclusion. Nimesil (Nimesulid) can be considered as a more safe drug than classical NSAIDs with smaller risk of serious gastroduodenal complications development in rheumatic pts with ulcer history. The results of the study allow to recommend Nimesulid as a drug of choice for treatment of pts with history of NSAID-induced gastropathy.

Objective. To assess Structum (chondroitin sulfate) efficacy in treatment of osteoarthritis in Republic of Karelia. Methods. 34 pts with osteoarthritis (mean disease duration 6,44±0,67 years) were included. Functional Leken score (FLS), pain at rest and at walk on visual analog scale (VAS), pts nonsteroidal anti-inflammatory drugs (NSAID) requirement (diclofenac daily requirement in mg), percent of pts refused NSAID treatment, achievement of clinically significant improvement (40% decrease of FLS and/or 50% decrease of NSAID requirement) were regarded as variables for the evaluation of therapy efficacy. Results. Structum administration in pts with osteoarthritis provided reduction of FLS, pain at rest and at walk, NSAID requirement and in some cases allowed to withdraw of NSAID completely. Structum has good safety and is effective in doctor and pts opinion. Conclusion. Structum is an effective drug for treatment of osteoarthritis.

Objective. To assess alflutop clinical efficacy and safety during long-term course treatment of knee osteoarthritis. Methods. 51 pts with definite knee osteoarthritis of I-III stage according to Kellgren-Lawrence classification were included in an open controlled study. 20 pts received 6 intra-articular injections of alflutop 2 ml with subsequent intramuscular treatment during 3 months. Such courses were repeated 6 months apart for 2 years. 31 pts of control group received nonsteroidal anti-inflammatory drugs (NSAID) only. Pain on visual analog scale, Leken functional score, changes of NSAID treatment and radiological picture were used for assessment of efficacy. Clinical examination was performed before and after every treatment course and 3 months after the last course. Results. Every alflutop treatment course provided significant stepwise decrease of pain with improvement of mobility, reduction of NSAID requirement and absence of osteoarthritis radiological progression. Doctor and pts clinical efficacy and safety assessment coincided. Conclusion. Alflutop is an effective drug for knee osteoarthritis treatment. It has anti-inflammatory and probably chondroprotective activity with good safety.

Lupus erythematosus (SLE) and systemic sclerosis (SS). Methods. 45 SLE and 44 SS pts were included. Some of them received antirheumatic drugs in combination with enalapril other were treated with antirheumatic drugs only. The pts were examined before and 6-12 months after the beginning of the treatment. Echocardioscopy and biomicroscopy of bulbar conjunctiva vessels were performed in all cases. Results. Treatment with enalapril improved state of all SLE and SS pts. The drug was well tolerated and provided decrease of dyspnoea and edema as well as blood pressure normalization. Most prominent improvement was evident 12 months after the beginning of enalapril treatment. Reduction of left ventricle myocardium hypertrophy, improvement of its diastolic function and reduction of structural changes of bulbar conjunctiva microcirculation were achieved at that time. Conclusion. Enalapril administration in combination with antirheumatic drugs improves state of SLE and SS pts as well as echocardiography and bulbar conjunctiva vessels biomicroscopy results. It can be recommended for treatment of these diseases.

Objective. To reveal frequency of reactivation of persistent HSV type 1, 2 and CMV infections and to estimate its role in pathogenesis of rheumatoid uveitis in children with JCA. Material and methods. 61 children with RU at the age of 5 - 15 years were studied. The duration of disease: 6 months - 13 years. Serum samples were tested in commercial enzyme linked immunnosorbent assay for detection of antibodies to unstructural early herpesviruses proteins (serologic evidence of acute infection). Cell-mediated immunity to HSV was measured by the in vitro proliferated response of peripheral lymphocytes (LP). Results. Reactivation of HSV and/or CMV persistent infections was established in 30 of 61 surveyed children (49 %) with RU. The activation of HSV type 1 infection (34,4 % of the patients) dominated. The antibodies to unstructured early HSV type 2 protein were detected in 8,2 %, to CMV- in 5 % of children. Conclusion. The correlation was observed between results of serologic investigations and clinical signs of RU.