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Z S Alekberova

Publications and source records attributed to Z S Alekberova.

At least 19 recordsLinked to original sources

[Catalytic autoantibodies as a new molecular instrument in rheumatological practice].

AIM: To compare clinicopathogenetic value of DNA-hydrolizing autoantibodies or DNA-abzymes in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). MATERIAL AND METHODS: We studied sera from 180 patients with SLE, 180 RA patients and 128 healthy donors matched by age and gender; assessed catalytic and cytotoxic activity of DNA-abzymes in patients with different variants of SLE and RA course. RESULTS: The highest catalytic and cytotoxic activities of DNA abzymes were observed in SLE patients. In SLE catalytic and cytotoxic activities of DNA abzymes ranged widely and their mean values depended on SLE activity in patients with systemic lesions. DNA-abzymes in RA patients showed lower catalytic and cytotoxic activities in relation to substrate DNA and target cells than in SLE. DNA-abzymes occurred most frequently in patients with high activity of RA, slow-progressive and lingering course of RA, especially in early development of visceral (extra-articular) pathology. Characteristic for DNA-abzymes in RA and SLE is the phenomenon of wide-range fluctuations due to factors determinating probability of induction of function of Ab-mediated catalysis and, therefore, incidence rates of DNA-abzymes, probably catalytic autoAb of the other specificity in a population of patients with systemic autoimmune diseases. CONCLUSION: The data indicate the validity of DNA abzymes use in clinical practice for realization of diagnostic and therapeutic programs in SLE and RA.

Adult↗

[Catalytic autoantibodies--a new molecular instrument in cardiology and ophthalmology].

AIM: To develop a conceptual model of using catalytic autoantibodies as diagnostic and monitoring tools in organ-specific autoimmune disorders. MATERIAL AND METHODS: A total of 99 patients (56 males and 43 females aged 21-52 years) with autoimmune myocarditis (AM) and 198 patients (77 males and 121 females aged 8-79 years) with autoimmune uveitis (A U) participated in the study. AM patients were examined for anticardiomyosin and anti-DNA autoantibodies (ACM, ADNAab), AU patients - for autoantibodies to S-antigen, IRBP, redopsin, phosphocine, autoDNA. RESULTS: AM patients had double level of DNA-binding autoantibodies. In 1/3 of them there was hydrolysing DNA and cytotoxic activity. In AU patients maximal titers were in Behcet's disease, sympathic ophthalmia, generalized uveitis and viral uveitis. CONCLUSION: Autoantibodies with different specificity and function including DNA-abzymes can be additional diagnostic and prognostic markers.

Adolescent↗

[The significance of cardiovascular risk factors and C-reactive protein to the development of atherosclerosis in women with systemic lupus erythematosus].

Compared with general population, women suffering from systemic lupus erythematosus (SLE) have signs of coronary artery disease (CAD) five to eight times more often, especially in young age. Early development of atherosclerosis in patients with SLE is caused by conventional cardiovascular risk factors and specific ones, associated with the disease and its therapy. A slight increase in such an inflammatory marker as C-reactive protein (CRP) is thought to reflect the presence of subclinical inflammation in the vascular wall, connected with atherosclerotic process. The authors analyzed the frequency of clinical and subclinical (an increase in the thickness of intima-media complex (IMC)) atherosclerotic manifestations, the summary coronary risk, the prevalence of conventional risk factors, and CRP level in 133 female patients with SLE and in 50 healthy donors. Compared to the control group, SLE patients were younger, developed cardiovascular diseases (CAD, stenocardia, myocardial infarction, and cerebral stroke (p = 0.05) as well as arterial hypertension more often, had higher levels of hs-CRP and triglycerides, and lower levels of high density lipoprotein cholesterol (HDLC). There was a positive correlation between hs-CRP level and the activity of the disease according to ECLAM score, ES value, IgG and IgM levels, hematological disturbances (anemia, leucopenia, and/or thrombocytopenia) , and a negative correlation with total cholesterol level, HDLC there was a moderate correlation between hs-CRP and a maximal IMC value.

Adult↗

[Vascular symptoms of Behcet's disease].

AIM: To characterize vascular symptoms of Behcet's disease (BD) in patients treated for the last 10 years in the Institute of Rheumatology. MATERIAL AND METHODS: Vascular symptoms of BD were studied in 151 patients with BD (mean age 33.5 +/- 9.5 years, duration of the disease 14.0 +/- 10.1 years, 104 males and 47 females, 67.4% carried HLA B51(5) antigen). Duplex vascular scanning was made to detect venous thrombosis. RESULTS: Thrombotic complications were found in 37 of 151 (24.5%) patients with BD (30 males and 7 females, mean age 37.1 +/- 9.1 years, mean duration of the disease 7.3 +/- 9.7 years). Venous thromboses prevailed (36 patients). Four males (2.6%) had arterial lesions: aneurysms of the iliac arteries (n = 1), thrombosis of the iliac artery (n = 1), pulmonary infarction and thrombosis of the pulmonary arteries (n = 2). Combination of venous and arterial manifestations occurred in 3 patients. One patient had thrombosis of the venous sinus, occlusion of the retinal vessels was diagnosed in 7 patients. CONCLUSION: Incidence of vascular disorders was observed in 1/4 of the patients. This corresponds to those observed worldwide and concerns venous thrombosis and other thromboses. Among the examinees, vascular disorders were associated with a young age, earlier development of thrombotic complications in males than in females.

Adult↗

[Achievements and prospects of clinical abzymology].

Catalytic autoantibodies (abzymes) are autoantibodies that are potentially ready to realize certain effects in the organism, first of all antibody-mediated catalysis and cytotoxicity. Natural abzymes with protolytic (protabzymes) and DNA-hydrolyzing DNA-abzymes) activity are of the greatest interest. The most impressive example of the catalytic activity of protabzymes is hydrolysis of specific proteins, revealed in patients with autoimmune diseases, such as bronchial asthma (vasoactive intestinal neuropeptide), autoimmune thyroiditis (thyroglobulin), multiple sclerosis (myelin basic protein), and autoimmune myocarditis (cardiomyosin). The pathogenic role of DNA-abzymes is not quite clear yet. However, it has been proven that they present a powerful regulator of apoptosis and other cytotoxicity mechanisms in systemic autoimmune diseases and tumors. The most promising is use of abzymes as illness activity markers, and as therapeutic agents capable of catalyzing specific proteins or activating antitumoral chemotherapeutic preparations.

Animals↗

[DNA-abzymes in rheumatoid arthritis: pathogenetic and clinical significance].

AIM: To study possible pathogenetic role and clinical significance of DNA-hydrolysing autoantibodies (autoAB) or DNA-abzymes in patients with rheumatoid arthritis. MATERIAL AND METHODS: Prevalence of DNA-abzymes and their catalytic activity were studied in 400 patients with rheumatoid arthritis (RA) and 88 healthy donors matched by age and gender. RESULTS: Associated with DNA-binding autoAB DNA-hydrolysing activity was detected in 41.5% cases of RA. DNA-abzymes were maximally active in men with rheumatoid factor (RF) and women without RF, while it was minimal in men without RF and women with RF. By catalytic activity there was no significant differences between patients with RF and without it. The highest catalytic activity of DNA abzymes was detected in patients with distinct extraarticular pathology. DNA-abzymes were also active in patients with x-ray stage III-IV of the disease in association with high prevalence of catalytic autoAB. DNA abzymes were also active in patients with RA activity stage II and III. CONCLUSION: It is possible to use DNA-abzymes in clinical practice for monitoring of the disease activity in RA.

Antibodies, Catalytic↗

[The condition of peripheral arteries in patients with systemic lupus erythematosus].

To evaluate the condition of peripheral arteries and its correlations with blood lipid spectrum and intake of glucocorticoids (GC), 53 female patients with SLE entered the study. Of them, 20 patients were GC untreated (group 1) while 33 ones took GC for a long time (group 2). Nine of 20 (45%) patients and 9 of 33 (27%) patients of group 1 and 2, respectively, had antiphospholipid syndrome (APS). Ultrasonography examined common carotid arteries (CCA), brachial arteries (BA), femoral arteries (FA) with measurement of the thickness of the intima-media complex (IMC). Lipid spectrum was examined with standard enzyme assay using kits by Boehringer Mannheim GmbH (Germany). Atherosclerotic plaques of carotid arteries were detected only in group 2. CCA IMC thickness reached 0.78 +/- 0.17 and 0.75 +/- 0.16 mm in groups 1 and 2, respectively. This thickness was significantly greater in SLE patients with APS than free of APS (0.89 +/- 0.18 and 0.87 +/- 0.18 mm in groups 1 and 2, respectively; 0.72 mm on the average in both groups, p = 0.02). Patients of group 1 with dyslipidemia showed a significant increase in CCA IMC (0.84 +/- 0.18 mm) vs patients with normolipidemia (0.70 +/- 0.13 mm, p = 0.042). Significantly increased levels of cholesterol, LDLP cholesterol and triglycerides were recorded in SLE patients of group 1 with CCA IMC > 0.8 mm. In group 1 there were significant positive correlations between CCA IMC and levels of total cholesterol, LDLP cholesterol, triglycerides (r = 0.78, 0.76 and 0.66 respectively, p < 0.05). Thus, atherosclerotic affection of the peripheral arteries in SLE is associated with long-term course of the disease, APS, dyslipidemia and intake of GC.

Adult↗

[Survival and prognostic factors of death risk in antiphospholipid syndrome: results of 8-year follow-up].

AIM: To evaluate survival and mortality in antiphospholipid syndrome (APS) as well as prognostic factors of APS deterioration. MATERIAL AND METHODS: We retrospectively studied 248 case histories of patients admitted to the Institute of Rheumatology for 8 years. Primary APS was diagnosed in 35 patients, SLE + APS (according to criteria of ACR, 1982)--in 122 patients and SLE without APS--in 91 patients. Mean age was 31.2 +/- 15.0 years (range from 14 to 63), median length of follow-up from the time of diagnosis was 11.9 +/- 5.4 years. During 8 year period all the patients annually and the latest 5 years at least twice a year were examined for the presence of IgG and IgM-anticardiolipin antibodies (aCL) and lupus anticoagulant (LA). Thrombotic events were verified with special techniques. RESULTS: Thirty-eight patients (15%) died during the follow-up period. Mean age of the decreased was 35.4 +/- 12.2 years (range 21-52 years) and the disease duration 8.6 +/- 8.2 years (range 0.6-20), the median length of the survival from the time of the diagnosis was 6.2 +/- 4.3 years. The 8-year survival for SLE patients without APS was 98%, for those with SLE + APS-75% and for patients with primary APS-83%. The presence of APS in SLE patients was significantly associated with high mortality (chi 2 = 12.3, freedom = 4, p = 0.006). Cox regression analysis revealed that the activity of the disease at onset, arterial thrombosis, especially recurrent, thrombocytopenia, valvular disease of the heart, capillaritis, digital necrosis and nephritis were independent risk factors for mortality (p < 0.05). CONCLUSION: Thus, long-term follow-up is necessary for patients with antiphospholipid antibodies especially with APS which lowers survival of SLE patients. Such patients need early corrective therapy to prevent thrombotic events.

Adolescent↗

[Clinico-immunological aspects of antiphospholipid syndrome].

The article contains a description of the clinical-and-immunological specific features of the secondary (concomitant with systemic lupus erythematosus-SLE) and primary anti-phospholipid syndrome (APS). We followed up a total of 280 patients with SLE and 74 patients with primary APS; 96 of 280 SLE patients were males and 184 of them were females, mean age--31.2 +/- 11.1, mean disease duration--8.6 +/- 7.2 years. The APS group consisted of 15 males and 59 females, mean age--35.6 +/- 7.2, mean disease duration--11.9 +/- 8.5 years. Antibodies to cardiolipin (aCL) and lupous anticoagulant (LA) were determined for all patients. Antibodies to IgM beta 2-GP I (IgM anti-beta-GP I) were determined for 102 patients and antibodies to IgG anti beta 2-GP I were determined for 153 patients. The level of antibodies to beta 2 GP I in blood serum was found by immune-enzyme assay (QUNTA Life). The secondary APS was diagnosed in 115 (41%) patients from among 280 SLE patients. The group of patients with SLE and without APS and the group with primary APS were age-matched, however, patients with APS were older and had a longer disease duration. The diagnosis was made in one half of patients with primary APS in 6 and more years after the disease onset. Thrombotic complications were found in 117 (42%) from among 280 SLE patients. They were encountered reliably more often in APS versus SLE (chi 2 = 131, p < 0.0001). Venous thrombosis in veins of lower extremities prevailed in APS, while thrombophlebitis of the surface shin veins was predominant in patients without APS. An important features of APS is occlusion of veins located in the liver with a subsequent development of Budd-Chiari syndrome (9 patients); in retinal veins (13 patients); thrombophlebitis in axillary veins (7 patients) and in abdominal-cavity veins (2 patients). Loss of pregnancy at various gestational stages was registered in medical histories of 83 (76%) from among 109 pregnant women. The frequency rate of fetus loss was higher in primary APS (32 of 40 cases) versus its secondary variation (49 of 75 cases) with chi 2 = 8.3, p = 0.004. Thrombocytopenia was detected reliably more often in patients with secondary APS (chi 2 = 36, p < 0.0001). The clinical signs of both primary and secondary APS were found to be similar. However, arterial and venous thromboses combined with the relapsing syndrome of fetus loss were more often registered in primary APS. The detection of highly positive aCL titers is of a significant diagnostic value versus the detection of its low- and mean-positive values. The study of anti-beta 2-GP I is also of certain importance for a more reliable diagnosis of APS.

Adult↗

[Atherogenic cholesterol-containing circulating immune complexes--one of the components of the serum in patients with systemic lupus erythematosus].

To estimate concentrations of cholesterol (CS) and immune complexes (IC) in patients with systemic lupus erythematosus (SLE), we examined 20 new SLE cases (all women, mean age 30.2 +/- 6.6 years, duration of the disease 2.6 +/- 1.5 years) with no history of corticosteroids treatment. The control group of 20 healthy patients was matched by age, body mass index and absence of risk factors. CS in IC precipitates was estimated by enzyme assays (kits by Boehrinnger Mannheim GmbH, Germany). The level of CS-containing IC (CS-IC) was significantly higher in SLE patients (11.9 +/- 2.7 mcg/ml) versus controls (6.0 +/- 2.2 mcg/ml, p < 0.05). The lipid spectrum was similar in the patients and controls. A significant positive correlation was registered between LDP CS and CS-IC levels (r = 0.774; p = 0.041). Association with other indices of blood lipid spectrum (total CS, triglycerides, HDP CS) was not observed. Thus, elevated level of CS-IC and association with LDP CS may be involved in atherogenesis of SLE patients.

Adolescent↗

Anti-DNA autoantibodies reveal toxicity to tumor cell lines.

Cytotoxicity of anti-DNA autoantibodies from sera of SLE and CLL patients was assayed on permanent cell lines L929, HL-60, Raji, and K562. L929 cells appeared to be the most sensitive to antibody treatment. DNA-hydrolyzing properties of the same autoantibody preparations were analyzed in parallel. The data obtained outlined the correlation between cytotoxicity and DNA-hydrolyzing properties of these autoantibodies. It was shown that treatment of the cells with cytotoxic anti-DNA autoantibodies induced internucleosomal DNA fragmentation and Annexin V binding to the cell surface characteristic of apoptotic pathway of cell death. A time-dependent profile of antibody-mediated toxicity to L929 cells suggested recruitment of at least two distinct mechanisms of cell death. The first peak of cell death observed in 3 h of incubation was completely inhibited by preincubation of cells with caspase inhibitor YVAD-CHO, while the second increase in cell mortality (18-30 h) persisted. Possible mechanisms for anti-DNA autoantibody cytotoxicity are discussed.

Antibodies, Antinuclear↗

[Corticosteroids in the treatment of secondary antiphospholipid syndrome].

The study of changes in the levels of antiphospholipid antibodies (aPL) and clinical manifestations of antiphospholipid syndrome (APS) in response to corticosteroids in secondary APS in patients with systemic lupus erythematosus (SLE) included 219 patients (28 males and 191 females) with APS observed at least for 3 years. aPL in the blood were measured each half of year. Mean age of the patients was 31.2 +/- 11.1 years, mean duration 8.6 +/- 5.2 years. The patients were divided into 3 groups: 54 patients (persistently positive) of group 1 had IgG-anticardiolipin antibodies (aCL) in the blood for the whole period of the observation, were positive by lupus anticoagulant (LA). 73 patients of group 2 were initially aPL-positive, but aPL levels fluctuated in the observation period from positive to negative and vice versa. 92 patients of group 3 had no aPL. For 3-year follow-up 25% of SLE patients were aPL positive, 42%--negative, aCL levels fluctuated in 33%. No APS symptoms were observed in 9%, 33% of groups 1 and 2, respectively, but APS symptoms appeared in the observation period. 10% of group 3 had some aPL-associated signs. aCL levels did not depend on mean daily dose of corticosteroids in groups 1 and 2 initially and within the follow-up. Frequency of LA, irrespective of corticosteroids dose, was significantly higher initially vs that in the follow-up. In spite of correlation between aPL positivity and SLE activity, depressed activity of the disease during the treatment did not entail a significant lowering of a PL levels in the follow-up. Thus, corticosteroids in APS in SLE patients influence LA more than aCL. SLE activity, corticosteroids therapy in APS are independent factors affecting aPL. Detection of aCL and LA in SLE is not the cause of prescription of high-dose corticosteroids.

Adult↗

[Cardiological aspects of the antiphospholipid syndrome. Part I. Valvular lesions in the primary and secondary antiphospholipid syndrome and systemic lupus erythematosus].

AIM: To assess prevalence of cardiac valvular lesions in patients with primary (P) antiphospholipid syndrome (APLS) and systemic lupus erythematosus (SLE) with and without secondary APLS. MATERIAL AND METHODS: Patients with PAPLS (n=56, 15 men and 41 women), SLE and APLS (n=88, 23 men, 65 women) and SLE without APLS (n=51, 19 men, 32 women) were followed up for 9 years. Serological markers of APLS were anticardiolipin antibodies and lupus anticoagulant. RESULTS: Prevalence of various heart defects was the highest in PAPLS (43%) compared with SLE with APLS (c2=5.6, p=0.001) and SLE without APLS (c2=9.3, p=0.0002). In secondary APLS prevalence of valvular involvement was 27% what was substantially more than in SLE without APLS (4%) (c2=7.2, p=0.0007). Changes of mitral valve cusps and mitral regurgitation were found in 33, 41 and 50% of patients with SLE, SLE with APLS and PAPLS, respectively. Pronounced mitral regurgitation and valve defects were significantly more frequent in patients with any APLS compared with those with SLE without APLS. Thickening of aortic cusps was significantly more frequent in patients with PAPLS compared with patients with SLE (with and without APLS). Changes of tricuspid valve were significantly more frequent in patients with any APLS. Progression of valvular pathology was observed in 2 patients with SLE and APLS after 4 and 5 years of follow up. During 9 years thrombotic complications developed in 8 patients with APLS and valvular lesions (6 strokes, 2 retinal thromboses). CONCLUSION: An association exists between presence of APLS and various cardiac valvular lesions. Lesions of aortic valve are associated with PAPLS: Development of valvular pathology in patients with SLE and PAPLS during follow up dictates the necessity to monitor echocardiographical parameters and titers of anticardiolipin antibodies.

Adolescent↗

[DNA-abzymes and their clinical significance in systemic lupus erythematosis].

AIM: To evaluate occurrence of DNA-abzymes with catalytic (DNA-hydrolysing) and cytotoxic properties in patients with systemic lupus erythematosus (SLE) for examination of clinical value of DNA-abzymes in diagnosis of autoimmune syndrome and apoptosis level in different variants of immunopathology. MATERIAL AND METHODS: The study group consisted of patients with verified SLE diagnosis (n = 120). They were compared to 72 patients with rheumatoid arthritis (RA), 82 patients with scleroderma systematica (SS), 60 patients with discoid lupus erythematosus (DLE), 88 patients with focal scleroderma (FS) and 198 autoimmune uveitis (AU) patients. 128 donors served control. Catalytic and cytotoxic activity of DNA-abzymes were determined by methods of molecular biology and enzymology. All the patients were examined for blood levels of IgG, IgM and IgA, anti-DNA, anti-Sm and other IgG-autoantibodies, CIC titers, phagocyting activity, content of main D-cell subpopulations. Key immunoregulatory indices were also estimated. RESULTS: DNA-abzymes were detected more often in SLE and RA patients. In SLE, catalytic and cytotoxic activities of DNA-abzymes reached their maximum. There was a correlation with leading clinicoimmunological signs of SLE. The disease was most severe with apparent immunopathology in patients with maximal catalytic and cytotoxic activity of DNA-abzymes. With lowering cytotoxic activity of DNA-abzymes more patients demonstrate low SLE activity without severe organic lesions and alleviated symptoms of immunopathology. CONCLUSION: An important role of DNA-abzymes in pathogenesis of SLE is shown. They are also valuable tools in diagnosis of various clinicoimmunological variants of the disease.

Apoptosis↗

[Antiphospholipid antibodies in Behcet's disease].

35 patients with Behcet's disease (BD) were examined for antiphospholipid antibodies (aPL). Elevated levels of antibodies to cardiolipin (aCL) were registered in 20% of the patients (aCL IgG and IgM in 11.4 and 8.6%, respectively). Low positivity of these antibodies prevailed (33.2 GPL and 41.2 MPL). Lupus anticoagulant was present in 6 patients. No distinct correlation was found between positivity by aPL and vascular disorders. It is inferred that aPL do not seem to play a leading role in thrombotic diathesis in BD. This diathesis is brought by a much more complicated and multifactor process.

Adolescent↗

[Leiden, G20210A mutations in prothrombin gene and antiphospholipid antibodies in systemic lupus erythematosus and antiphospholipid syndrome].

AIM: To estimate incidence rate of Leiden mutation in factor V gene, prothrombin gene mutation responsible for replacement of G for A in position 20210 (G20210A) of its 3'-end noncoding part in patients with systemic lupus erytheamtosus (SLE) and antiphospholipid syndrome (APS) and their relationships with antiphospholipid antibodies (aPL): lupus anticoagulant (LA) and anticardiolipin antibodies (aCL). MATERIALS AND METHODS: The trial included 33 patients (2 males and 31 females) aged 20-62 years (mean age 32.7 +/- 9.8 years). 29 patients suffered from SLE, 17 of them had also APS (criteria by G. R. V Hudhes). 3 patients had primary APS, 1 female had hemorrhagic vasculitis. IgG and IgM-aCL were detected by enzyme immunoassay. In revealing mutation, DNA was used isolated from peripheral blood by standard methods based on polymerase chain reaction (PCR). Primary screening of Leiden mutation was made according to Bertina et al. with Mnl I restrictase. The mutation was confirmed by an original technique with allele-specific primers. G20210A mutation in the prothrombin gene was determined with restrictase Taq I after introduction of artificial restriction site in PCR product. The patients were divided into 2 groups. Group 1 incorporated 12 patients with SLE without APS. Group 2--21 patients with APS (17 with SLE + APS, 3 with primary APS and 1 with hemorrhagic vasculitis). RESULTS: Patients of group 1 had neither thrombotic complications nor Leiden mutation. Two patients of group 2 had heterozygous Leiden mutation. Both females were aPL-positive and had previously recurrent thrombophlebitis. One of them had also recurrent disorders of cerebral circulation. None of the examinees had any G20210A mutations in the prothrombin gene. CONCLUSION: Detection of genetic defects in APS provide arguments in the dispute about the necessity, duration and choice of anticoagulant therapy. If patients with APL syndrome appeared to have besides aPL also genetic defects in coagulation, this will enable identification of patients at high risk of thrombosis which need permanent administration of anticoagulants among which only low-molecular ones or glycosaminoglycanes are indicated. Mutation in gene of factor V is absolute contraindication to phenilin and quamarines.

Adult↗