Serum biomarkers and their relationship to axial spondyloarthritis associated with inflammatory bowel diseases.

Spondyloarthritis (SpA) constitute a group of chronic inflammatory immune-mediated rheumatic diseases characterized by genetic, clinical, and radiological features. Recent efforts have concentrated on identifying biomarkers linked to axial SpA associated with inflammatory bowel disease (IBD), offering predictive insights into disease onset, activity, and progression. Genetically, the significance of the HLA-B27 antigen is notably diminished in ankylosing spondylitis (AS) associated with IBD, but is heightened in concurrent sacroiliitis. Similarly, certain polymorphisms of endoplasmic reticulum aminopeptidase (ERAP-1) appear to be involved. Carriage of variant NOD2/CARD15 polymorphisms has been demonstrated to correlate with the risk of subclinical intestinal inflammation in AS. Biomarkers indicative of pro-inflammatory activity, including C-reactive protein (CRP) along with erythrocyte sedimentation rate (ESR), are among the consistent predictive biomarkers of disease progression. Nevertheless, these markers are not without limitations and exhibit relatively low sensitivity. Other promising markers encompass IL-6, serum calprotectin (s-CLP), serum amyloid (SAA), as well as biomarkers regulating bone formation such as metalloproteinase-3 (MMP-3) and Dickkopf-related protein 1 (DKK-1). Additional candidate indicators of structural changes in SpA patients include matrix metalloproteinase-3 (MMP-3), vascular endothelial growth factor (VEGF), tenascin C (TNC), and CD74 IgG. Fecal caprotein (f-CLP) levels over long-term follow-up of AS patients have demonstrated predictive value in anticipating the development of IBD. Serologic antibodies characteristic of IBD (ASCA, ANCA) have also been compared; however, results exhibit variability. In this review, we will focus on biomarkers associated with both axial SpA and idiopathic intestinal inflammation, notably enteropathic spondyloarthritis.

Circulating miRNAs in hand osteoarthritis.

OBJECTIVE: Hand osteoarthritis (OA) is a frequent musculoskeletal disorder with an increasing prevalence during ageing. This study aimed to evaluate circulating microRNAs (miRNAs) in the plasma of patients with hand OA compared with age- and sex-matched healthy control subjects. METHODS: In total, 238 participants (96 with erosive and 73 with non-erosive hand OA patients and 69 healthy control subjects) were included in this study. All patients underwent clinical examinations, including self-reported measures (AUSCAN and Algofunctional index). Radiographs of both hands were scored with the Kallman scale. The profile of miRNAs in plasma was screened using TaqMan™ Low-Density Array, and candidate miRNAs were validated on two quantitative real-time PCR (qRT-PCR) systems (QuantStudio and SmartChip). RESULTS: Of all the 754 miRNAs, 40 miRNAs were different between hand OA patients and healthy control subjects in the screening cohort. Following the two-phase validation process, three miRNAs (miR-23a-3p, miR-146a-5p, and miR-652-3p) were increased in patients with hand OA compared with healthy control subjects and were associated with the AUSCAN sum score and AUSCAN pain. Furthermore, an inverse correlation of miR-222-3p with the Kallman radiographic score was found. The expression of miRNAs did not differ between erosive and non-erosive hand OA. CONCLUSION: The profile of circulating miRNAs could unveil candidate biomarkers associated with hand OA symptoms. Longitudinal studies are required to determine the role of miRNAs in hand OA.

A decrease in serum 1,25(OH)2D after elective hip replacement and during bone healing is associated with changes in serum iron and plasma FGF23.

OBJECTIVE: Although calcitriol is essential for bone healing, its serum concentrations are low after hip surgery, and they continue to decline during bone healing. This study aimed to test the hypothesis of an association of changes in calcitriol production with the status of fibroblast growth factor 23 (FGF23) and iron deficiency after elective hip replacement for coxarthrosis. METHODS: In this prospective study, we measured the biomarkers of 17 patients undergoing elective hip replacement on admission, on the first day after surgery, and at the regular check-up after 48 ± 8 days. The serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, transferrin, ferritin, parathyroid hormone, intact plasma FGF23 (iFGF23) and C-terminal FGF23 (cFGF23) were determined. RESULTS: In our patients who underwent elective hip replacement, significant correlations existed between the percent change in the conversion rate of 25(OH)D to 1,25(OH)2D, plasma intact to C-terminal FGF23 ratio, and serum iron. CONCLUSIONS: The production of calcitriol is compromised after elective hip replacement surgery, leading to reduced levels of active vitamin D in the serum. Significant correlations between the percent change in the conversion rate of 25(OH)D to 1,25(OH)2D, plasma intact to C-terminal FGF23 ratio, and serum iron on the first day as well as 7 weeks after surgery could inspire future studies to determine whether and how calcitriol deficiency should be corrected, especially in fracture cases.

Circulating miR-145 as a marker of therapeutic response to anti-TNF therapy in patients with ankylosing spondylitis.

Circulating miRNAs appear promising therapeutic and prognostic biomarkers. We aimed to investigate the predictive value of circulating miRNAs on the disease outcome following anti-TNF therapy in patients with ankylosing spondylitis (AS). Our study included 19 AS patients assessed at baseline (M0), after three (M3) and twelve months (M12) of therapy. Total RNA was isolated from plasma. A comprehensive analysis of 380 miRNAs using TaqMan Low Density Array (TLDA) was followed by a single assay validation of selected miRNAs. All AS patients had high baseline disease activity and an excellent response to anti-TNF therapy at M3 and M12. TLDA analysis revealed the dysregulation of 17 circulating miRNAs, including miR-145. Single assay validation confirmed that miR-145 is significantly downregulated at M3 compared to baseline. The decrease in the levels of miR-145 from M0 to M3 negatively correlated with the change in BASDAI from M0 to M3; and positively correlated with disease activity improvement from M3 to M12 as per BASDAI and ASDAS. The predictive value of the early change in miR-145 and levels of miR-145 at M3 were further validated by Receiver operating curves analysis. We show thatthe early change in circulating miR-145 may be a predictor for the future outcome ofAS patients treated with TNF inhibitors. Patients with a more significant decrease in miR-145 levels may show further significant improvement of disease activity after 12 months. Monitoring the expression of miR-145 in plasma in AS patients may, therefore, influence our therapeutic decision-making.

Decrease in serum calcitriol (but not free 25-hydroxyvitamin D) concentration in hip fracture healing.

OBJECTIVE: To assess the decrease in serum calcitriol concentrations after hip fracture. METHODS: Serum concentrations of calcitriol, 25(OH)D, parathyroid hormone (PTH), directly measured free 25(OH)D, and indices of bone formation were measured in elderly patients with hip fracture (HF) and patients with elective hip replacement (EHR) at admission and after 7 weeks. RESULTS: A total of 45 patients with HF and 17 patients with EHR completed this prospective study. Baseline serum calcitriol levels were ≤ 60 pmol/l in 26% of the HF patients. After 7 weeks, they significantly decreased (p < 0.001). In patients with EHR, serum calcitriol was within the reference range in all but one patient and did not change during the 7-week recovery phase. Seven weeks after HF, a significant positive relationship was observed between the change in calcitriol and serum 25(OH)D concentration (r = 0.385, p = 0.009) and free 25(OH)D (r = 0.296, p = 0.048), and a decrease in calcitriol during recovery was associated with a decrease in serum PTH (p = 0.038). Seven weeks after HF, changes in both serum PTH and serum 25(OH)D concentrations contributed to the prediction of changes in serum calcitriol (R2 = 0.190, p = 0.012). CONCLUSIONS: Unlike patients with EHR, subjects with HF had low serum 25(OH)D and low free 25(OH)D concentrations at admission, while their serum 1,25D levels were relatively elevated. Decreases in circulating calcitriol levels in the 7 weeks following hip surgery were associated with a resolution of secondary hyperparathyroidism and low availability of free 25(OH)D.

Elevated Tenascin-C Serum Levels in Patients With Axial Spondyloarthritis.

This study aimed to examine serum tenascin C (TNC) in different subsets of axial spondyloarthritis (axSpA) patients. Sixty-one patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA and 20 healthy subjects (HS) were included in study. Based on imaging, patients were classified as non-radiographic (n=16) and radiographic (n=45) axSpA. TNC serum levels were determined by ELISA. Disease-related factors including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP) levels, were determined. TNC levels were elevated in axSpA patients [535.3 (457.7-677.2) ng/ml] compared to HS [432.1 (329.1-565.9) ng/ml, p=0.007]. Dividing axSpA into radiographic and non-radiographic subsets, the difference in TNC was observed between the radiographic subset and HS [535.3 (434.5-677.2) vs. 432.1 (329.1-565.9) ng/ml, p=0.022]. TNC levels did not correlate with disease activity measures (serum CRP or BASDAI). Nevertheless, the weak correlation of TNC levels with different disease stages (r=0.25, p=0.025) was found, with the highest levels in patients with syndesmophytes. TNC levels are elevated across various subsets of axSpA, and although not related to systemic disease activity, TNC levels might reflect chronic structural spinal changes in axSpA patients. However, its specific role in bone metabolism should be elucidated in further studies.

Efficacy and tolerability of injectable collagen-containing products in comparison to trimecaine in patients with acute lumbar spine pain (Study FUTURE-MD-Back Pain).

Low back pain (LBP) represents an important subgroup of vertebrogenic pain with estimated prevalence around 80 %. Locally acting injectable collagen for topical application has recently extended the limited range of treatment options. The aim of the study was to evaluate the efficacy and safety of injectable collagen in patients with LBP. Patients suffering from LBP (< three months) were enrolled. They were administered either collagen 4 ml or trimecaine 1 % 4 ml in the form of subcutaneous paravertebral injections into eight pre-specified points (0.5 ml per each point) in the following schedule: two administrations in the first and second week, one in the third week. The pain intensity, Thomayer distance, Oswestry disability index, Lasseque test, quality of life, consumption of rescue medication and safety were evaluated. Exertional and rest pain, evaluated by a visual analogue scale, gradually decreased in both groups. Both treatments showed a statistically significant improvement in mobility and quality of life. The consumption of paracetamol as a rescue medication was significantly lower in patients treated with collagen than in the group treated with trimecaine (p=0.048). The analgesic efficacy of locally acting injectable collagen, as well as an analgesic sparing effect when compared to local anesthetics were demonstrated.

Chronic Low Back Pain: Current Pharmacotherapeutic Therapies and a New Biological Approach.

Chronic low back pain (CLBP) syndrome represents one of the leading causes of long-term disability worldwide. The prevalence of CLBP has been rising significantly in relation to increasing average life expectancy. CLBP results from chronification of acute low back pain. There are many factors contributing to the CLBP crisis; common etiopathogenetic factors include e.g., functional blockage of intervertebral joints. The treatment of CLBP is complex. An important part of treatment consists of pain pharmacotherapy, for which several groups of drugs are used. The problem lies in the side effects of many of these traditionally used medications. Therefore, new and safer treatment methods are being sought. Innovative options for CLBP pharmacology include injections containing collagen, which can be combined with other traditionally used drugs, which helps reduce dosages and increase the overall safety of CLBP therapy.

Smoking and response to rituximab in rheumatoid arthritis: results from an international European collaboration.

OBJECTIVES: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). METHOD: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. RESULTS: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). CONCLUSION: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.

Factors associated with the orthopaedic surgeon's decision to recommend total joint replacement in hip and knee osteoarthritis: an international cross-sectional study of 1905 patients.

OBJECTIVE: To determine factors associated with orthopaedic surgeons' decision to recommend total joint replacement (TJR) in people with knee and hip osteoarthritis (OA). DESIGN: Cross-sectional study in eleven countries. For consecutive outpatients with definite hip or knee OA consulting an orthopaedic surgeon, the surgeon's indication of TJR was collected, as well as patients' characteristics including comorbidities and social situation, OA symptom duration, pain, stiffness and function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), joint-specific quality of life, Osteoarthritis Research Society International (OARSI) joint space narrowing (JSN) radiographic grade (0-4), and surgeons' characteristics. Univariable and multivariable logistic regressions were performed to identify factors associated with the indication of TJR, adjusted by country. RESULTS: In total, 1905 patients were included: mean age was 66.5 (standard deviation [SD], 10.8) years, 1082 (58.0%) were women, mean OA symptom duration was 5.0 (SD 7.0) years. TJR was recommended in 561/1127 (49.8%) knee OA and 542/778 (69.7%) hip OA patients. In multivariable analysis on 516 patients with complete data, the variables associated with TJR indication were radiographic grade (Odds Ratio, OR for one grade increase, for knee and hip OA, respectively: 2.90, 95% confidence interval [1.69-4.97] and 3.30 [2.17-5.03]) and WOMAC total score (OR for 10 points increase: 1.65 [1.32-2.06] and 1.38 [1.15-1.66], respectively). After excluding radiographic grade from the analyses, on 1265 patients, greater WOMAC total score was the main predictor for knee and hip OA; older age was also significant for knee OA. CONCLUSION: Radiographic severity and patient-reported pain and function play a major role in surgeons' recommendation for TJR.

Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study.

BACKGROUND: Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). METHODS: Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes. FINDINGS: We identified three types of treatment response trajectories: 'gradual responders' (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; 'rapid responders' (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; 'inadequate responders' (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p=0.03), and EULAR good or moderate responses at 1year was much higher among 'rapid responders' (p<0.001). INTERPRETATION: Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.

Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan-European Registry Analysis.

OBJECTIVE: To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA). METHODS: We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated. RESULTS: We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P < 0.001 and HR 0.78 [95% CI 0.68-0.90], P < 0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P < 0.001). CONCLUSION: Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.

European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update.

BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations. METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated. RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used. CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion.

The impact of patient heterogeneity and socioeconomic factors on abatacept retention in rheumatoid arthritis across nine European countries.

BACKGROUND: There are substantial differences in accessibility to biological disease modifying antirheumatic drugs (bDMARDs) across countries. The objective of this study was to analyse the impact of patient demographics, disease characteristics and gross domestic product (GDP) on abatacept (ABA) retention in patients with rheumatoid arthritis (RA) treated in clinical practice. METHODS: Data from nine European observational RA cohorts of patients treated with ABA were pooled. Kaplan-Meier analysis was used to compare drug retention across registries. Specific causes of drug retention were investigated using competing risks multivariate Cox regression. RESULTS: A total of 3961 patients treated with ABA, with 6188 patient-years of follow-up, were included. Patients in the different national registries had similar demographic features, but varied in baseline disease characteristics. ABA drug retention differed between countries, with median drug retention rates ranging from 1.2 to more than 6 years. The differences in drug retention were marginally explained by disparities in disease characteristics, while the national GDP per capita was strongly associated with drug retention (correlation coefficient -0.74; p=0.02). CONCLUSIONS: Patient characteristics at ABA initiation vary across Europe, probably reflecting differences in eligibility criteria and prescription patterns. However, the difference in ABA drug retention between countries was not primarily explained by disparities in patient characteristics. Lower ABA retention was observed in countries with a more liberal access to bDMARDs and higher GDP. National differences need to be accounted for when pooling data on treatment with bDMARDs from various countries.

[Correction of kyphotic deformity of the cervical spine in ankylosing spondylitis using pedicle subtraction osteotomy of the seventh cervical vertebra]. / Korekce kyfotické deformity krcní pátere pri ankylozující spondyloartritide pedikl subtrakcní osteotomií sedmého krcního obratle.

PURPOSE OF THE STUDY: The aim of the study is to present the technique of pedicle subtraction osteotomy (PSO) of the seventh cervical vertebra (C7) for correction of rigid kyphotic deformity of the cervicothoracic junction (C/Th) in patients with severe ankylosing spondylitis (AS).. MATERIAL AND METHODS: The PSO technique for correction of rigid deformity of the C/Th spine was used in five patients with the aim to restore their ability of horizontal vision. The follow-up in all patients lasted two years at least. Clinical assessment of treatment results was based on the patients' neurological status and their satisfaction with the correction achieved. Improvement in a vertical 2) line of sight was evaluated using the angle measured between the forehead-chin line and the vertical (FCv angle) in a lateral view photograph of the standing patient. The achieved correction of kyphotic deformity was assessed by comparing the pre-operative Cobb's angle between the second cervical and the fourth thoracic vertebra with the post-operative one. RESULTS: The average operative time was 4 hours (range, 3.5 to 5 h). The average blood loss was 1600 ml (range, 800 to 2100 ml). On the average, the FCv angle was reduced by 45.2° and Cobb's angle was corrected) by 54.6°. All patients were satisfied with the degree of correction achieved and reported alleviation of neck pain. none of the patients showed any significant loss of correction or neurological deterioration at two-year follow-up. DISCUSSION: The theoretical and technical principles of corrective osteotomy at the C7 level performed for rigid kyphotic deformity of the spine at the C/Th junction are presented in our group of patients. Our results give support to the superiority of instrumented PSO used currently over the previous techniques. In accordance with the relevant literature data, attention is drawn to a relatively higher risk of this procedure in comparison with corrective surgery performed at the other spinal levels. CONCLUSIONS: Corrective osteotomy of a rigid kyphotic deformity at the C/Th spine level in AS patients involves a complex reconstructive surgical procedure. The PSO technique reduces the risk of injury to the visceral structures ventral to the spine, and provides optimal conditions for bone healing at the site of vertebral body resection. If the patient heals well, a successful PSO procedure will markedly improve the quality of his/her life.

Decrease in serum interleukin-21 levels is associated with disease activity improvement in patients with recent-onset rheumatoid arthritis.

Interleukin-21 (IL-21) plays an important role in the pathogenesis of rheumatoid arthritis (RA). The aim of our study was to assess serum levels of IL-21 in patients with recent-onset RA in relation to disease activity and response to treatment. We analyzed serum levels of IL-21 in 51 RA patients, both before and 12 weeks after the initiation of treatment and in 36 healthy individuals. Disease activity was assessed at baseline and at weeks 12 and 24 using the Disease Activity Score for 28 joints, serum levels of C-reactive protein, and the total swollen joint count. We found that IL-21 levels were not increased in patients with recent-onset RA compared with healthy controls, but they had significantly decreased from baseline to week 12 during treatment. Baseline levels of IL-21 significantly correlated with measures of disease activity (p<0.02 for all). Although IL-21 levels did not predict achievement of remission, decrease in IL-21 levels correlated with improvement in disease activity after 12 weeks (p<0.02) and also after 24 weeks (p<0.04) of treatment. Our data suggest that circulating IL-21 levels may serve as a biomarker of disease activity and better outcome in early phase of RA.

Seroprevalence and specificity of NMO-IgG (anti-aquaporin 4 antibodies) in patients with neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric manifestations are present in 30-40% of patients with systemic lupus erythematosus (SLE). Recently, antibodies to aquaporin-4 (termed AQP4-Ab, or NMO-IgG), a water channel protein, were reported to be present in a subset of patients with SLE and neurological involvement. To evaluate the syndrome specificity and prevalence of serum NMO-IgG/anti-AQP4 antibodies in patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Sera of 76 patients with SLE and neurological symptoms, 50 of whom met the ACR case definitions of NPSLE, were tested for AQP4-Ab in an indirect immunofluorescence assay employing HEK293 cells transfected with recombinant human AQP4. Only one of the examined sera was positive for NMO-IgG/AQP4-Ab. This patient suffered from TM, ranging over two vertebral segments on spinal MRI. None of the 75 NPSLE without TM was found to be seropositive for NMO-IgG/AQP4-Ab. NMO-IgG/AQP4-Ab in NPSLE were present only in a patient with TM and were not detectable in NPSLE patients with other neurological manifestations. Testing for NMO-IgG/AQP4-Ab positivity should be considered in patients presenting with SLE and TM. Non-longitudinally extensive lesions do no not exclude NMO-IgG/AQP4-Ab in patients presenting with SLE and TM.

Novel adipokine fibroblast growth factor 21 is increased in rheumatoid arthritis.

Fibroblast growth factor-21 (FGF-21) has been recently characterized as a new adipokine. The aim of this study was to assess FGF-21 levels in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationship between FGF-21, disease activity and metabolic status. The levels of FGF-21 in serum and synovial fluid samples from 38 patients with RA and 42 control individuals with OA were determined by ELISA. Patients were assessed for disease activity using the disease activity score (DAS28), a serum glucose and lipid profile. Age, sex and BMI-adjusted FGF-21 levels in the serum (p=0.024) and synovial fluid (p=0.010) samples were significantly higher in patients with RA when compared with OA. The levels of FGF-21 in the serum significantly correlated with the levels in the synovial fluid. Serum and synovial fluid FGF-21 levels adjusted for confounders correlated positively with C-reactive protein. The levels of FGF-21 were positively correlated with BMI in patients with RA; however, the levels were not associated with disease activity or lipid profiles. Furthermore, serum FGF-21 levels were significantly higher in seropositive compared with seronegative RA patients. This work shows that patients with seropositive RA have increased levels of FGF-21. The results suggest that FGF-21 is related to BMI but not disease activity or lipid profiles in patients with RA.

Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis.

OBJECTIVE: Dickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its lower levels are linked to new bone formation. The aim of this study was therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association with the severity of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). METHODS: Serum levels of total and functional DKK-1 and C-reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age and sex-matched controls. Plain radiographs of the cervical and thoracic spine were performed, and the diagnosis of DISH was defined using the Resnick criteria. Patients were divided into three groups based on spinal involvement. Bone mineral density (BMD) and bone turnover markers were evaluated in patients with DISH. RESULTS: The levels of total serum DKK-1 were significantly lower in patients with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of DKK-1 were associated with more severe spinal involvement in DISH, independent of age, sex, disease duration, CRP, bone turnover markers or BMD. However, these findings were less significant for functional DKK-1. CONCLUSION: These observations indicate that DKK-1 may play a significant role in bone formation during DISH.