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B Rozman

Publications and source records attributed to B Rozman.

At least 19 recordsLinked to original sources
PubMed2006

Accelerated atherosclerosis in pre-menopausal female patients with rheumatoid arthritis.

Increased mortality due to cardiovascular disease in rheumatoid arthritis (RA) patients was reported. Using B-mode ultrasonography we compared intima-media thickness (IMT) and plaque occurrence (indicators of asymptomatic atherosclerosis) in the carotid arteries in 70 pre-menopausal, female RA patients and 40 controls. Correlations with different risk factors were evaluated. The IMT values were higher in RA patients (0.59 mm vs. 0.47 mm, P < 0.0001) and they had more plaques (P = 0.023). In RA patients higher levels of sensitive CRP (P < 0.0001), ICAM (P < 0.0001), VCAM (P < 0.0001), IL-2 (P < 0.001), IL-6 (P = 0.009) and TNF-alfa (P < 0.01) were found. A correlation between IMT and triglycerides (P = 0.018) and a negative correlation between IMT and HDL cholesterol (P = 0.037) were found. With multiple regression analysis the association between IMT and sensitive CRP (P = 0.027) and presence of plaques and apolipoprotein B (P = 0.028) was established. The results indicate that even pre-menopausal, female RA patients had accelerated atherosclerosis. Chronic systemic inflammation may play an important role in atherogenesis.

Adult↗
PubMed2006

Annexin A5 binding to giant phospholipid vesicles is differentially affected by anti-beta2-glycoprotein I and anti-annexin A5 antibodies.

OBJECTIVES: Anti-phospholipid antibodies have been recognized to play a role in vascular thrombosis and pregnancy morbidity. They were first thought to be directed to phospholipids, but it is now known that the majority of pathogenic antibodies recognizes epitopes on phospholipid-binding plasma proteins such as beta2-glycoprotein I (beta2GPI) or possibly also annexin A5 (ANXA5). The mechanism of their prothrombotic action is still not completely understood. The aim of the present study was to observe the effect of antibodies against ANXA5 (aANXA5) and antibodies against beta2GPI (abeta2GPI) on the binding of ANXA5 to the negatively charged phospholipid membrane. METHODS: Giant phospholipid vesicles (GPVs) were used as a simple model of the membrane surface. GPVs composed of phosphatidylserine and phosphatidylcholine were produced in an aqueous medium. A single GPV was transferred to the solution containing ANXA5 conjugated with Alexa Fluor 488 (FANXA5) and (i) aANXA5 or abeta2GPI and (ii) different concentrations of abeta2GPI together with beta2GPI. The emission of the fluorescent light from the GPV surface, as the result of FANXA5 binding, was measured. RESULTS: Beta2GPI together with abeta2GPI reduced the binding of FANXA5 to GPVs. On the contrary, aANXA5 enhanced the binding of ANXA5 to the GPV surface. CONCLUSIONS: Our results point to the competition between FANXA5 and complexes of beta2GPI-abeta2GPI for the same binding sites and therefore support the hypothesis of the disruption of the ANXA5 protective shield on procoagulant phospholipid surface. The influence of increased cell surface ANXA5 concentration in the presence of aANXA5 on coagulation needs to be further studied.

Annexin A5↗
PubMed2006

Serum amyloid A in autoimmune thrombosis.

The objectives of this study were (1) to determine how levels of serum amyloid A (SAA), high sensitivity C-reactive protein (CRP) and interleukin-6 (IL-6) correlate to autoimmune diseases in patients with or without thrombosis, and (2) to discuss the parameters that influence the relative SAA values. SAA, CRP and IL-6 concentrations were determined by enzyme linked immunosorbent assay (ELISA). 84 patients with secondary antiphospholipid syndrome (SAPS), primary antiphospholipid syndrome (PAPS), systemic lupus erythematosus with antiphospholipid antibodies (SLE+aPL), SLE, venous thrombosis (VT), arterial thrombosis (AT) were compared to healthy donors (n=60). The percentages of patients above cut-off were highest in the SAPS, SLE and SLE+aPL groups. Significant differences were observed between healthy donors and inflammatory groups of patients (SAPS and SLE+aPL) in all three measured parameters. SAA and CRP were shown to be correlated to a greater extent in SAPS patients than SLE+aPL patients. In summary, this cross-sectional, retrospective, small study and accompanying clinical considerations limit the ability to make definite conclusions. SAA would not serve as a useful marker for venous, arterial thrombosis or PAPS (pro-coagulant events). It could however, be a good predictor of progression from a non-inflammatory thrombotic condition to an inflammatory one.

Amyloid↗
PubMed2006

Changes in avidity and specificity of IgG during electro-oxidation. Relevance of binding of antibodies to beta2-GPI.

The immune response may be changed due to altered proteins or modifications of immunoglobulins, including oxidative processes. The susceptibility to oxidative modifications depends greatly on amino-acid moiety composition due to chemical characteristics (instability) of their side-chains. Initial steps of oxidation may change the specificity and avidity of immunoglobulins due to chemical alteration of the hypervariable region. The oxidation of antibodies increases the hydrophilic nature of the paratopes and makes them more susceptible for the binding to cationic surfaces even without the strong surface-to-surface fitting. The electro-oxidation of IgG significantly changes the immunoreactivity and specificity of IgG fractions, regardless of the initial immunoreactivity to a specific autoantigen also in healthy persons. Data are presented on changes in the immunoreactivity as well as the avidity of antibodies against beta2-glycoprotein I after being exposed to direct current. ELISA measurements showed increased reactivity of anti-beta2-glycoprotein I antibodies at the beginning and various, fluctuating results after prolonged exposure to electro-oxidation. Inter-individual differences in chemical stability of immunoglobulins and patient's antioxidative status may influence the range of their alterations and their impact on health/disease balance.

Antibody Affinity↗
PubMed2005

Ultrasonographic changes of major salivary glands in primary Sjogren's syndrome. Diagnostic value of a novel scoring system.

OBJECTIVES: To reveal typical ultrasonographic (US) changes in major salivary glands associated with Sjogren's syndrome (SS) and to determine the diagnostic value of a novel US scoring system. METHODS: In 218 consecutive patients with suspected SS, US of both parotid and submandibular salivary glands was performed besides the regular diagnostic procedure following the American-European Consensus Group criteria of 2002. Five US parameters were assessed: echogenicity, inhomogeneity, number of hypoechogenic areas, the hyperechogenic reflections and clearness of the borders of the salivary gland. The grades of these five parameters for all four salivary glands were summed. The final US score ranged from 0 to 48. RESULTS: SS was established in 68 patients. The remaining 150 subjects, in whom SS was not confirmed, constituted our control group. All five US parameters were significantly associated with SS. The patients with SS had significantly higher US scores than those not diagnosed with SS (P<0.01). Setting the cut-off US score at 17 resulted in the best ratio of specificity (98.7%) to sensitivity (58.8%). CONCLUSIONS: Well-defined US changes in the major salivary glands summarized in our novel scoring system were typical of SS patients. Advanced structural changes found on US imaging almost invariably represent SS salivary gland involvement.

Adult↗
PubMed2005

Avidity of anti-beta-2-glycoprotein I antibodies.

The terms affinity and avidity are often used indiscriminately, despite clearly differing. Since affinity refers to monovalent binding of antibodies to a monovalent epitope, the majority of data on the binding of anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) characterized their avidity rather than affinity. Anti-beta2-GPI were generally believed to be of low avidity, but heterogeneous avidity of patients' IgG anti-beta2-GPI has been demonstrated. High avidity anti-beta2-GPI monoclonals were reported to possess higher pathogenicity than low avidity anti-beta2-GPI. Polyclonal high avidity anti-beta2-GPI were found to be more common in patients with antiphospholipid syndrome (APS) and associated with thrombosis. Some conformational changes of beta2-GPI are required for the binding of polyclonal anti-beta2-GPI to the antigen: neither high density of the antigen nor high avidity of the anti-beta2-GPI alone is sufficient for the recognition. Avidity of anti-beta2-GPI should be considered in any attempt of inter-laboratory standardisation and/or evaluation of anti-beta2-GPI enzyme-linked immunosorbent assay (ELISA).

Animals↗
PubMed2005

Anti-phospholipid antibodies following vaccination with recombinant hepatitis B vaccine.

This study was undertaken to evaluate the possible role of hepatitis B recombinant vaccine inducing the synthesis of IgG and IgM anti-cardiolipin antibodies (aCL), antibodies against beta(2)GPI (anti-beta(2)GPI), lupus anti-coagulant (LA), anti-nuclear antibodies and antibodies against extractable nuclear antigens (anti-ENA). The study population consisted of 85 healthy students (63 female, 22 male; mean age 20.8 years), vaccinated with three doses of recombinant DNA hepatitis B vaccine. One month after vaccination with the first dose of hepatitis B vaccine a minority of vaccinated individuals showed changes in IgG or IgM aCL or anti-beta(2)GPI or LA activity (P < 0.001). Among subjects in whom changes of IgG anti-beta(2)GPI were observed, a significantly higher number of increased (8/85) than decreased (2/85) values were found (P < 0.01). Analyses of paired data showed that differences in aCL or anti-beta(2)GPI levels before vaccination or 1 month later did not reach statistical significance. In two people aCL transitorily reached medium positivity after the first dose of hepatitis B vaccine with a drop 5 months later. Similar evident anti-beta(2)GPI fluctuation was also observed in one person. Another participant was initially low positive for IgG anti-beta2GPI and the levels were increasing after vaccination. Two participants became positive for anti-nuclear antibodies during 6 months' follow-up. There were no sex-dependent differences in tested antibodies observed and no associations between levels of aPL and levels of anti-HBV antibodies. We conclude that HBV can induce aPL, although rarely. In genetically susceptible individuals or together with some other triggers such combination might confer the risk of developing a continuous autoimmune response in an individual.

Adult↗
PubMed2005

A comparison of the sensitivity of diagnostic criteria for polymyalgia rheumatica.

OBJECTIVE: To compare the performance of the several different diagnostic criteria sets currently in use for polymyalgia rheumatica (PMR). METHODS: 213 patients attending eight rheumatological centres in eight different European countries were studied. All had recently been referred and were considered by the senior investigator at each centre, selected because of their experience in treatment of PMR, to have this condition. By use of a standard international proforma, the requisite diagnostic points in each criteria set were sought. Sensitivity for each criterion from each set was then calculated, as well as the sensitivity of each criteria set as a whole. RESULTS: Of four criteria sets compared, the Bird (1979) criteria performed best with a sensitivity of 99.5%, and the Hunder (1982) criteria second best, with sensitivity of 93.3%. These both performed significantly better than the two other criteria sets, though each of these was admittedly developed for rather specialised reasons. CONCLUSIONS: Although this study compares homogeneity, we suggest the Bird 1979 or Hunder 1982 criteria should be used whenever possible. Studies that have used alternative criteria may have less sensitivity in diagnosis.

Adult↗
PubMed2005

Avidity of anti-beta2-glycoprotein I and thrombosis or pregnancy loss in patients with antiphospholipid syndrome.

We aimed to evaluate avidity of anti-beta(2)-glycoprotein I antibodies (anti-beta(2)-GPIs) in patients with antiphospholipid syndrome (APS) at the time of acute thrombotic events or pregnancy loss as compared with clinical event-free periods. To do so, 69 sera samples from 16 patients (6 with primary APS and 10 with APS secondary to systemic lupus erythematosus ) were selected on the basis of anti-beta(2)-GPI positivity. Avidity of IgG anti-beta(2)-GPIs was determined by chaotropic enzyme-linked immunosorbent assay (ELISA), using increased NaCl concentration during antibody binding. High, heterogeneous, and low-avidity anti-beta(2)-GPIs were measured in APS patients, with no clear pattern regarding the time of thrombotic events or pregnancy failure. In general, anti-beta(2)-GPI avidity did not change substantially during disease course. We concluded that avidity of anti-beta(2)-GPIs appears to be a rather stable parameter in an individual APS patient. Considering the previously shown association of high-avidity anti-beta(2)-GPIs with venous thrombosis, avidity of anti-beta(2)-GPIs may be a better predictor of predisposition to thrombosis and unsuccessful pregnancy than levels of antiphospholipid antibodies, which may fluctuate over time owing to several factors.

Abortion, Spontaneous↗
PubMed2004

Binding of high-avidity anti-beta2-glycoprotein I antibodies.

OBJECTIVES: We studied the influence of different binding conditions on the interaction between high- or low-avidity IgG anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) and beta2-GPI, which was either free in solution or bound to microtitre plates or nitrocellulose membranes. METHODS: Sera from 30 patients with antiphospholipid syndrome and/or systemic lupus erythematosus were selected on the basis of anti-beta2-GPI positivity. Avidity of IgG anti-beta2-GPI was determined by chaotropic ELISA, using increased NaCl concentration during the antibody binding. Immunodetection on nitrocellulose membrane followed reducing or non-reducing sodium dodecyl sulphate-polyacrylamide gel electrophoresis (PAGE) of beta2-GPI. In converted, non-reducing PAGE, the preparation with high-affinity Fab fragments (obtained by papain digestion) was subjected to electrophoresis, while purified beta2-GPI was used as the sample in immunodetection. RESULTS: Anti-beta2-GPI antibodies of high, low or heterogeneous (low and high) avidity were found in 5/30, 9/30 and 16/30 sera, respectively. The density of beta2-GPI, which was 20-30 times higher on the nitrocellulose membrane than on the surface of ELISA plates, was not sufficient for the recognition of the antigen by anti-beta2-GPI: 2/5 high-avidity samples reacted only with non-reduced beta2-GPI, 3/9 low-avidity samples recognized only denatured and reduced beta2-GPI, and 1/16 samples with heterogeneous-avidity antibodies reacted with reduced and non-reduced beta2-GPI. CONCLUSIONS: Our results suggest that neither high density of the antigen nor high avidity of the antibodies (or Fab fragments) alone was sufficient for the binding of anti-beta2-GPI to beta2-GPI. Some conformational modifications and, consequently, exposed neo-epitopes are required for the recognition of beta2-GPI by polyclonal anti-beta2-GPI antibodies.

Antibody Affinity↗
PubMed2004

A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis.

OBJECTIVE: To assess the efficacy of interferon beta (IFN beta) in combination with methotrexate in treatment of patients with rheumatoid arthritis. METHODS: 209 patients with active rheumatoid arthritis, who had been on methotrexate for at least six months and at a stable dose for four weeks before study entry, were randomised in double blind fashion to receive placebo (0.05 ml or 0.5 ml), IFN beta 2.2 microg (0.05 ml), or IFN beta 44 microg (0.5 ml), given subcutaneously three times weekly for 24 weeks. The primary efficacy measure was a change in radiological scores at week 24. The secondary endpoint was the proportion of patients who met the ACR 20% improvement criteria at the end of the study. Synovial biopsy specimens were obtained before and after treatment from a subset of patients. Immunohistochemistry was used to detect the presence of inflammatory cells and the results were measured by digital image analysis. Collagen crosslinks were measured in urine at different times throughout the study. RESULTS: Analysis of radiological scores and clinical variable showed no changes in any of the groups, and there were no differences between the groups. On microscopic analysis of synovial tissue there was no significant change in the scores for infiltration by inflammatory cells after IFN beta treatment. Urinary levels of collagen crosslinks were unchanged between the treatment groups. CONCLUSIONS: At the doses tested, treatment with IFN beta three times weekly in combination with methotrexate did not have a clinical or radiological effect in patients with rheumatoid arthritis.

Adult↗
PubMed2004

Estimation of antiphospholipid antibodies in a prospective longitudinal study of children with migraine.

The aim of this study was to determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in children with migraine. The values of anticardiolipin (aCL) and antibeta2 glycoprotein I (antibeta2GPI) antibodies were assayed by an ELISA method in 52 children with migraine and 22 children with tension-type headache. The control group consisted of 61 apparently healthy children at regular preventive visits. Two monoclonal beta2GPI dependent aCL (HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was determined by a modified dilute Russell viper venom time test. Persistently positive aPL were observed during the follow-up in 16.3% of children with migraine (9.3% for aCL, 7.0% for antibeta2GPI and 0% for LA) and in 16.7% of children with tension-type headache (11.1% for aCL, 5.6% for antibeta2GPI and 0% for LA). The prevalence of aPL did not differ significantly between patient groups and healthy children. The prevalence of aPL does not appear to be increased in an unselected group of children with migraine, however, the possible role of aPL in individual cases of paediatric migraine can not be excluded.

Adolescent↗
PubMed2004

EULAR randomised controlled trial of pulse cyclophosphamide and methylprednisolone versus continuous cyclophosphamide and prednisolone followed by azathioprine and prednisolone in lupus nephritis.

OBJECTIVE: To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone, followed by azathioprine, in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus (SLE). METHODS: A multicentre randomised controlled trial was conducted between June 1992 and May 1996 involving eight European centres. All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis. All received corticosteroids in addition to cytotoxic drugs, as defined in the protocol, for two years. The trial was terminated after four years as recruitment was disappointing. RESULTS: 32 SLE patients with lupus nephritis were recruited: 16 were randomised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine. Mean duration of follow up was 3.7 years in the continuous group (range 0 to 5.6) and 3.3 years in the pulse group (range 0.25 to 6). Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis. Two patients in the continuous therapy group developed end stage renal failure requiring dialysis, but none in the intermittent pulse therapy (p = 0.488; NS). There were similar numbers of side effects and withdrawals from treatment in both groups. There were three deaths: two in the intermittent pulse therapy group and one in the continuous therapy group. CONCLUSIONS: There was no statistically significant difference in efficacy and side effects between the two regimens. Infectious complications occurred commonly, so careful monitoring is required during treatment.

Administration, Oral↗
PubMed2004

Incidence of primary Sjogren's syndrome in Slovenia.

OBJECTIVE: To determine the annual incidence of primary Sjögren's syndrome (pSS) in Slovenia. METHODS: All patients admitted to our department of rheumatology or referred to our outpatient clinic between 1 January 2000 and 31 December 2002 owing to sicca symptoms or because of a suspicion of SS were examined. Our rheumatological department is the only tertiary referral centre for the Ljubljana region, which has a population of 599 895 Caucasian people. All patients were evaluated by the validated European criteria for SS. The exact 95% confidence interval (CI) based on binomial distribution was created for the incidence estimate. RESULTS: 248 patients were examined; 71 of them (28.6%; 65 women, 6 men) were diagnosed as having pSS. Their mean (SD) age was 51.3 (14.5) years (range 19-78). The average annual incidence for pSS in our study population was calculated as 3.9 cases per 100 000 inhabitants (95% CI 1.1 to 10.2). CONCLUSION: The estimated annual incidence of pSS in Slovenia is 3.9/100 000.

Adult↗