Association of tumor necrosis factor-α (G-308A) genetic variant with matrix metalloproteinase-9 activity and joint destruction in early rheumatoid arthritis.

Matrix metalloproteinases (MMPs) are the key enzymes responsible for the joint destruction. Their activity is regulated by the level of proinflammatory cytokines. The aim of this study was to examine the impact of TNF-α G-308A polymorphism on MMP-9 levels in blood plasma (BP) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and their role in progression of joint destruction. One hundred thirty-four subjects were enrolled in this study. TNF-α G-308A polymorphism was determined using PCR-RFLP method. ELISA assay was used for the detection of MMP-9 activity in BP and SF. Joint damage was estimated by hands and feet radiography. Larsen score and annual changes in LS were used for quantitative evaluation of joint destruction and radiographic progression of disease. MMP-9 activity in BP and SF was significantly higher in RA compared to controls, as well as in SF of patients with erosive compared to nonerosive RA. Faster radiographic progression and increased MMP-9 activity in BP and SF were detected in the group A (GA or AA genotype carriers) compared to the group G (GG genotype carriers). However, statistical significance was revealed only for MMP-9 activity in SF (p < 0.05). MMP-9 activity in BP and SF is significantly higher in RA patients compared to patients with osteoarthritis. The presence of TNF-α-308A allele is associated with increased MMP-9 activity in SF of patients with early RA and may be a predictor of rapid radiographic progression of disease.

Anti-dsDNA, anti-nucleosome and anti-C1q antibodies as disease activity markers in patients with systemic lupus erythematosus.

INTRODUCTION: In spite of the growing number of reports on the study of anti-nucleosome and anti-C1q antibodies, there are still controversies on their significance as disease activity markers in patients with systemic lupus erythematosus (SLE) and their use in everyday clinical practice. OBJECTIVE: Our aim was to assess the presence of anti-dsDNA, anti-nucleosome and anti-C1q antibodies in SLE patients, as well as to establish their sensitivity, specificity, positive and negative predictive value, and their correlation with SLE and lupus nephritis clinical activity. METHODS: The study enrolled 85 patients aged 45.3 +/- 9.7 years on the average, with SLE of average duration 10.37 +/- 7.99 years, hospitalized at the Institute,,Niska Banja" during 2011, and 30 healthy individuals as controls. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). In all examinees the levels of anti-dsDNA, anti-nucleosome and anti-C1q antibodies were measured using the ELISA method with Alegria Test Strips Orgentec (Germany). RESULTS: Patients with active lupus nephritis had a higher presence of anti-C1q antibodies and higher co-positivity of anti-dsDNA, anti-nucleosome, and anti-C1q antibodies compared to those with inactive lupus nephritis (77.77% vs. 21.74%; p < 0.01). SLE patients with SLEDAI > or = 11 had a higher presence of antinucleosome (93.75% vs. 64.15%; p < 0.01) and anti-C1q antibodies (46.87% vs. 22.64%; p<0.05), as well as a higher mean level of anti-nucleosome antibodies (107.79 +/- 83.46 U/ml vs. 57.81 +/- 63.15 U/ml; p < 0.05), compared to those with SLEDAI of 0-10. There was a positive correlation between the SLEDAI and the level of anti-dsDNA (r=0.290; p<0.01), anti-nucleosome (r = 0.443; p < 0.001), and anti-C1q antibodies (r = 0.382; p < 0.001). Only anti-C1q antibodies demonstrated correlation with proteinuria (r = 0.445; p < 0.001). CONCLUSION: Anti-nucleosome and anti-C1q antibodies demonstrated association with SLE and lupus nephritis activity, suggesting their potential usefulness in making predictions about lupus nephritis and assessment of disease activity.

The clinical significance of antibody determination to cyclic citrullinated peptides in systemic sclerosis.

INTRODUCTION: Anti-citrullinated peptides antibodies (ACPA) are present in 80% of sera of rheumatoid arthritis (RA) patients with high specificity for diagnosis and prediction for the development of early erosive arthritis. A few studies have reported a low frequency ACPA in systemic sclerosis (SSc) patients with the presence of arthritis. OBJECTIVE: The aim of our study was to determine the frequency of ACPA in systemic sclerosis (SSc) patients, their correlation with clinical manifestations and radiographic features. METHODS: The study included 82 patients with SSc, mean age 54.4 years, 59 with the limited (ISSc) and 23 with the diffuse (dSSc) form of the disease. The control group included 28 healthy age and sex matched subjects. ACPA and rheumatoid factor (RF) were determined in all SSc patients and healthy subjects in whom standard radiography of hands and wrists was also done. RESULTS: The presence of ACPA was detected in 11 (13.4%) of SSc patients. Their level was not increased in any of the controls. Positive RF was found in 15.9% of SSc patients. Arthritis was present in 17.1%, as well as marginal bone erosions. There was a statistically significant association between positive ACPA and arthritis (p < 0.0001) and positive ACPA and marginal bone erosions (p = 0.0002). CONCLUSION: The research confirmed the correlation between ACPA with clinical signs of arthritis and radiographic damage of hand joints. ACPA is a useful diagnostic marker in the identification of SSc patients with arthritis and anatomic bone damage enabling the use of adequate therapy in order to prevent joint damage and poor quality of life.

[Influence of balneophysical therapy on activity, functional capacity, and quality of life in patients with rheumatoid arthritis].

INTRODUCTION: It has been well known that balneophysical therapy has a therapeutic effect on clinical and biological parameters of disease activity in the patients with rheumatoid arthritis (RA). OBJECTIVE: To determine the influence of balneophysical therapy on functional capacity, activity and quality of life of the patients with RA primarily treated with some of disease modifying antirheumatic drugs. METHODS: The study enrolled 73 patients with RA treated with some of disease modifying antirheumatic drugs (Methotrexate in 85% of patients). During hospitalization at the Clinical Rheumatologic Department of the Institute "Niska Banja", the patients were treated, beside the medicamentous therapy, by hydrotherapy (oligomineral, homeothermic, low radioactive water), mineral peloid therapy, electrotherapy and kinesiotherapy. Before and after balneotherapy, the patients filled in the Health Assessment Questionnaire (HAQ) and the Quality of Life Rheumatoid Arthritis (QOL-RA) scale. The Disease Activity Score (DAS) 28 was used to measure the disease activity before and after balneotherapy. A possible value of HAQ was from 0 to 3, and QOL-RA from 0 to 10. RESULTS: The mean value of the duration of balneophysical therapy was 14.7 +/- 4.8 days. We found significant improvement of functional capacity in the patients with RA. The average HAQ score before balneotherapy was 1.07 +/- 0.61, and 0.86 +/- 0.55 after balneotherapy, which was statistically significantly lower (p < 0.05). DAS 28 after balneotherapy was also statistically significantly lower than DAS 28 before balneotherapy: the mean value of DAS 28 before therapy was 6.30 +/- 0.81 and after therapy 5.48 +/- 0.75 (p < 0.001). The quality of life significantly improved after balneophysical therapy: the mean value of QOL-RA scale before therapy was 5.38 +/- 1.62 and after therapy 7.35 +/- 1.81 (p < 0.05). CONCLUSION: Balneophysical therapy, when properly dosed, is an effective, adjuvant therapy in the patients with RA of mild disease activity. Balneophysical therapy has a positive influence on disease activity, functional capacity and quality of life in the patients with rheumatoid arthritis.

[Effects of natural factors of Niska Banja spa on indexes of mobility of vertebral column in patients with ankylosing spondylitis].

INTRODUCTION: Ankylosing spondilitis (AS) is a disease from a group of seronegative spondyloarthropathies with the prevalence of 0.1% affecting mainly young males, which also gives sociomedical significance to the disease. Among all inflammatory arthropathies, AS is the most suitable for balneotherapy. Thermomineral water of the Niska Banja spa is homeothermic, oligomineral, alkaline, low radioactive radon water and also, in conjunction with mineral peloid, is considered to be optimal for this indication. OBJECTIVE: Our aim was to investigate the effects of natural factors of the Niska Banja spa as a part of complex treatment on the indexes of mobility of the vertebral column in the patients with AS. METHODS: The study enrolled 40 patients with the average age of 48.0 +/-14.82 years and the average duration of disease of 16.9 +/- 6.42 years. Patients were treated with hydro- and peloidotherapy during the average of 17.23 +/- 2.71 days. At the beginning and at the end of treatment, a number of indexes of spinal mobility were measured. The statistical significance of differences was calculated using the Student's t-test. RESULTS: All of the measured indexes were better after balneotherapy reaching statistically significant differences in regard to the wall-to-occiput distance (p < 0.05), the index of sagittal mobility of the cervical (p < 0.05) and lumbar (p < 0.005) spine. CONCLUSION: The application of natural factors of the Niska Banja spa during complex treatment of the patients with AS is accompanied with the objective increase of the spine mobility.

Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries.

OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.