Ondřej Pecha

Decreases in serum levels of S100A8/9 (calprotectin) correlate with improvements in total swollen joint count in patients with recent-onset rheumatoid arthritis

IntroductionThe aim of this study was to examine the serum levels of S100 proteins and to evaluate their role in patients with recent-onset rheumatoid arthritis (RA).MethodsSerum levels of S100A8/9 and S100A12 were analysed in 43 patients with recent-onset RA, both before and three months after the initiation of conventional treatment, as well as in 32 healthy individuals. Disease activity was assessed based on serum levels of C-reactive protein (CRP), the Disease Activity Score for 28 joints (DAS28) and the total number of swollen joints count for 66 joints (SJC).ResultsThe levels of serum S100A8/9 and S100A12 were significantly higher in patients with recent-onset RA compared to the levels in healthy individuals (P < 0.0001) and normalised after three months of treatment. Using age- and sex-adjusted analysis, S100A8/9 levels were correlated with CRP (r = 0.439, P < 0.01), DAS28 (r = 0.501, P = 0.002) and SJC (r = 0.443, P = 0.007), while S100A12 was less significantly correlated with these parameters. Higher levels of S100A8/9 at baseline predicted improvement in the levels of CRP and SJC over time. Moreover, decreases in serum S100A8/9 were associated with decreased serum levels of CRP (r = 0.459, P = 0.005) and improvements in SJC (r = 0.459, P = 0.005). In multiple linear regression analyses, decreases in S100A8/9 but not CRP were significant predictors for improvements in SJC (P = 0.001).ConclusionsThis study is the first to show normalisation of elevated S100 proteins in patients with recent-onset RA after the initiation of conventional treatment. Therefore, S100A8/9 might potentially be a predictive marker for improvement in the total number of swollen joints in patients in the early phase of RA.

PPARA intron polymorphism associated with power performance in 30-s anaerobic Wingate Test.

To date, polymorphisms in several genes have been associated with a strength/power performance including alpha 3 actinin, ciliary neurotrophic factor, vitamin D receptor, or angiotensin I converting enzyme, underlining the importance of genetic component of the multifactorial strength/power-related phenotypes. The single nucleotide variation in peroxisome proliferator-activated receptor alpha gene (PPARA) intron 7 G/C (rs4253778; g.46630634G>C) has been repeatedly found to play a significant role in response to different types of physical activity. We investigated the effect of PPARA intron 7 G/C polymorphism specifically on anaerobic power output in a group of 77 elite male Czech ice hockey players (18–36 y). We determined the relative peak power per body weight (Pmax.kg−1) and relative peak power per fat free mass (W.kg−1 FFM) during the 30-second Wingate Test (WT30) on bicycle ergometer (Monark 894E Peak bike, MONARK, Sweden). All WT30s were performed during the hockey season. Overall genotype frequencies were 50.6% GG homozygotes, 40.3% CG heterozygotes, and 9.1% CC homozygotes. We found statistically significant differences in Pmax.kg−1 and marginally significant differences in Pmax.kg−1 FFM values in WT30 between carriers and non-carriers for C allele (14.6±0.2 vs. 13.9±0.3 W.kg−1 and 15.8±0.2 vs. 15.2±0.3 W.kg−1 FFM, P = 0.036 and 0.12, respectively). Furthermore, Pmax.kg−1 FFM strongly positively correlated with the body weight only in individuals with GG genotypes (R = 0.55; p<0.001). Our results indicate that PPARA 7C carriers exhibited higher speed strength measures in WT30. We hypothesize that C allele carriers within the cohort of trained individuals may possess a metabolic advantage towards anaerobic metabolism.

Decreased circulating visfatin is associated with improved disease activity in early rheumatoid arthritis: data from the PERAC cohort.

Objective To evaluate circulating visfatin and its relationship with disease activity and serum lipids in patients with early, treatment-naïve rheumatoid arthritis (RA). Methods Serum visfatin was measured in 40 patients with early RA before and after three months of treatment and in 30 age- and sex-matched healthy individuals. Disease activity was assessed using the Disease Activity Score for 28 joints (DAS28) at baseline and at three and 12 months. Multivariate linear regression analysis was performed to evaluate whether improved disease activity is related to serum visfatin or a change in visfatin level. Results Serum visfatin was significantly elevated in early RA patients compared to healthy controls (1.92±1.17 vs. 1.36±0.93 ng/ml; p = 0.034) and significantly decreased after three months of treatment (to 0.99±0.67 ng/ml; p<0.001). Circulating visfatin and a change in visfatin level correlated with disease activity and improved disease activity over time, respectively. A decrease in visfatin after three months predicted a DAS28 improvement after 12 months. In addition, decreased serum visfatin was not associated with an improved atherogenic index but was associated with an increase in total cholesterol level. Conclusion A short-term decrease in circulating visfatin may represent an independent predictor of long-term disease activity improvement in patients with early RA.

Adipokine profile is modulated in subcutaneous adipose tissue by TNFα inhibitors in patients with rheumatoid arthritis

A protective effect of obesity showing that increased adiposity protects against radiographic joint damage in patients with rheumatoid arthritis (RA) has been reported.1 2 Recently, adipokines were suggested as a molecular link explaining this paradoxical association.3,–,5 The levels of serum adiponectin and visfatin have been shown to be associated with increased, radiographic joint damage in RA, while leptin is associated with reduced radiographic joint damage.4 5 Therefore, we tested whether tumour necrosis factor α (TNFα) inhibitor therapy, which prevents joint damage in majority of patients with RA, may be associated with a change in the local production of adipokines in subcutaneous adipose tissue (SAT). SAT samples were obtained from the same abdominal region by aspiration with a bioptic needle in nine patients with RA prior to and 6 months after the treatment with etanercept. Adipose tissue samples were …

The level of fatty acid-binding protein 4, a novel adipokine, is increased in rheumatoid arthritis and correlates with serum cholesterol levels

OBJECTIVE To assess the expression of the novel adipokine Fatty Acid Binding Protein-4 (FABP4) in synovial tissues, serum and the synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationships among FABP4, disease activity and metabolic status. METHODS FABP4 levels were measured in the serum and synovial fluid of 40 patients with RA and 40 control patients with OA. The disease activity score (DAS28), C-reactive protein (CRP) levels and serum lipids were assessed in patients with RA. Immunohistochemical analysis and confocal microscopy were used to study the expression and cell-specific distribution of FABP4 in synovial tissues. RESULTS The age, sex and body mass index (BMI) adjusted levels of FABP4 were significantly higher in the serum (p=0.001) and synovial fluid (p=0.005) of patients with RA when compared to OA patients. FABP4 levels were higher in females than in males and correlated positively with body mass index (BMI) in patients with RA. Independent of confounders, FABP4 levels correlated with total cholesterol and LDL cholesterol in patients with RA, but not in OA patients. FABP4 levels were not affected by disease activity. Furthermore, the increased expression of FABP4 that was otherwise restricted to synovial fibroblasts, macrophages and B-cells was noted in RA patients at levels higher than that observed in OA patients. CONCLUSIONS The observed elevation of FABP4 levels in RA patients and the positive correlation of the adipokine to cholesterol suggest that FABP4 may represent a potential link between RA and the increased risk of atherosclerotic changes.

High levels of metastasis-inducing S100A4 protein and treatment outcome in early rheumatoid arthritis: data from the PERAC cohort

Abstract The aim of this study was to evaluate the role of S100A4 as a biomarker in patients with early rheumatoid arthritis (RA). S100A4 levels were measured in 59 patients with early RA and in 41 healthy controls. The association between the S100A4 levels and the treatment outcome after 12 months was determined using multivariate regression analysis. Serum S100A4 levels were significantly higher in the patients with early RA than in the healthy subjects and significantly decreased after 3 months of treatment. Diseases activity at 12 months was significantly higher in female patients who had initially high levels of S100A4. Persistently high S100A4 levels predicted poor treatment outcome and S100A4 may thus represent promising biomarker for assessing treatment response in patients with RA.

The metastasis promoting protein S100A4 levels associate with disease activity rather than cancer development in patients with idiopathic inflammatory myopathies

IntroductionThe aim was to evaluate S100A4 protein as a biomarker of disease activity and potential cancer development in patients with myositis.MethodsSerum levels of S100A4 were determined in 43 dermatomyositis (DM), 39 polymyositis (PM) and 22 cancer associated myositis (CAM) patients as well as in 77 healthy controls. The associations between S100A4 levels, inflammation, disease activity, muscle strength and cancer development were evaluated.ResultsAll myositis patients had significantly higher serum levels of S100A4 protein compared to healthy controls (median (IQR): 31.5 (17.4 to 59.5) versus 23.8 (14.5 to 33.7) ng/ml, P <0.05). In patients with PM, serum levels of S100A4 protein were significantly higher than in healthy controls (41.6 (24.2 to 123.1) versus 23.8 (14.5 to 33.7) ng/ml; P <0.001) as well as in patients with DM (26.7 (11.3 to 47.5) ng/ml; P <0.05). The levels of S100A4 were comparable between myositis with and without cancer. In all myositis patients, serum S100A4 levels correlated with MYOsitis disease ACTivity assessment (MYOACT) score (r = 0.34; P = 0.001), constitutional (r = 0.30; P = 0.003), pulmonary (r = 0.43; P = 0.0001) and extramuscular disease activity (r = 0.36; P = 0.0001), as well as with creatine phosphokinase (r = 0.27; P = 0.015) and lactate dehydrogenase (r = 0.37; P = 0.002) or c-reactive protein (CRP) levels (r = 0.24; P = 0.038). Multiple regression analysis showed significant association between S100A4 serum levels and extramuscular disease activity (β = 0.552; P = 0.002) in PM patients and with MYOACT (β = 0.557; P = 0.003) and CRP levels (β = 0.391; P = 0.029) in DM patients.ConclusionsCirculating levels of S100A4 are elevated in patients with myositis and associate with several disease activity parameters, particularly with extramuscular components. No relation between S100A4 levels and presence of cancer associated myositis was found.

Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis

BackgroundB-cell activating factor of the tumour necrosis factor family (BAFF) plays a role in autoantibody production and is elevated in dermatomyositis (DM) and anti-Jo-1-positive polymyositis (PM). We investigated the inter-relationships between serum levels of BAFF, anti-Jo-1 autoantibodies, and disease activity.MethodsSerum levels of BAFF and anti-Jo-1 antibodies measured by enzyme-linked immunosorbent assay (ELISA) were compared to levels of myoglobin, creatine kinase (CK), aminotransferases (alanine (ALT) and aspartate (AST)), C-reactive protein (CRP), and disease activity assessed by the Myositis Disease Activity Assessment Tool in 63 anti-Jo-1 antibody-positive DM/PM patients. Serial serum samples collected at 2 (46 cases) and 3–5 time points (23 cases) were included. Relationships between BAFF, anti-Jo-1, disease activity, CRP, and their longitudinal changes were evaluated using correlation analysis, multiple regression (MR), path analysis (PA), and hierarchical linear models (HLM).ResultsCross-sectional assessment demonstrated significant correlations between the levels of BAFF and anti-Jo-1 antibodies which were associated with levels of CK, myoglobin, AST, and CRP, as well as multivariate associations between BAFF, anti-Jo-1 antibodies, and CK levels. PA revealed direct effects of anti-Jo-1 antibodies on CK (β = 0.41) and both direct (β = 0.42) and indirect (through anti-Jo-1 antibodies; β = 0.17) effects of BAFF on CK. Changes in levels of both BAFF and anti-Jo-1 between two time points (Δ) were associated with Δmyoglobin and Δaminotransferases and changes of BAFF correlated with ΔCK, Δcutaneous, Δmuscle, Δglobal, and Δskeletal disease activities.The longitudinal analysis showed a high intra-individual variability of serum levels of BAFF over time (97%) which could predict 79% of the variance in anti-Jo-1 levels. The anti-Jo-1 variability was explained by inter-individual differences (68%). The close longitudinal relationship between levels of BAFF, anti-Jo-1, and disease activity was supported by high proportions of their variance explained with serum levels of CK and CRP or pulmonary and muscle activities.ConclusionOur findings of associations between levels of BAFF and anti-Jo-1 antibodies in serum and myositis activity suggest a role of this cytokine in disease-specific autoantibody production as part of disease mechanisms, and support BAFF as a potential target for intervention in anti-Jo-1-positive myositis patients.

Using sporting migrants to build secondary sport: a 12 year case study of Czech basketball

This study examines the effects of the sport migration that occurred over a 12 year period in the secondary sport of basketball in the Czech Republic, in terms of its effect on the popularity of the sport within the culture. The factors of fan attendance and youth membership are isolated and measured quantitatively, using multi-level analysis within teams, between teams and at a federation level. The study was carried out in order to measure the effect of the use of immigrant athletes from an individual team management perspective and from a league growth perspective. It was found that while foreigners displace national athletes, fans were attracted to the use of foreigners and youth were attracted to play the game. The use of foreigners had the most significant correlations at the between team level to home attendance and final placement in the league. Multi-level analysis was used to show that the use of foreigners can be a facilitator for federations and team management to build the popularity of secondary sports in a culture, with certain limitations. This quantitative study of a secondary sport is an addition to the majority of the literature on sport migration, which has been largely conducted on primary sports from a qualitative, sociological perspective.

THU0528 Decrease in Circulating Visfatin Levels is Associated with Disease Activity Improvement in Early Rheumatoid Arthritis

Background Identification of novel molecules contributes to better understanding of rheumatoid arthritis (RA) pathogenesis and offers promise for comprehensive identification of novel biomarkers that would allow monitoring of disease activity and individualize prognosis of RA patients. Visfatin may represent a novel biomarker of disease severity. Serum visfatin levels are elevated in RA, may be associated with the degree of inflammation, clinical disease activity and radiographic joint damage. Objectives To assess circulating visfatin and its relationship with disease activity and serum lipids in patients with early treatment-naïve RA and to evaluate the effect of treatment with conventional synthetic DMARDs on visfatin levels. Methods Serum levels of visfatin were analysed in 40 patients with early RA before and after three months of treatment and in 30 age- and sex-matched healthy individuals. Disease activity was assessed by the Disease Activity Score for 28 joints (DAS28) at baseline and at months 3 and 12. Multivariate linear regression analysis was performed to evaluate whether disease activity improvement can be related to serum circulating visfatin or to a change of visfatin levels. Results Visfatin serum levels were significantly elevated in early RA patients compared with healthy controls (1.92±1.17 vs. 1.36±0.93 ng/ml; p=0.034) and significantly decreased after three months of treatment (to 0.99±0.67 ng/ml; p<0.001). Circulating visfatin and change in visfatin levels correlated with disease activity and disease activity improvement over time, respectively. Visfatin decrease after three months predicted DAS28 improvement after 12 months (p=0.031, adjusted R2=10.1%). In addition, decrease of serum visfatin levels was not associated with improved atherogenic index, but was negatively associated with the increase of total cholesterol levels. Conclusions Short-term decrease in circulating visfatin levels may represent independent predictor of long-term disease activity improvement in patients with early RA. Acknowledgements This study was supported by Internal Grant Agency of Ministry of Health of the Czech Republic NT/13696-4 and Research Project No. 00023728. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4092