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ID PMID Title PublicationDate abstract
25844966 Balancing the benefits and risks of low-dose glucocorticoid in rheumatoid arthritis. 2015 Jan Glucocorticoids have potent anti-inflammatory and immunomodulatory effects and are widely use in the management of rheumatoid arthritis in combination with other synthetic and with biological disease-modifying anti-rheumatic drugs. Concerns about the risk of adverse effects of glucocorticoids, especially if they are given at higher dosages and for a longer time, hamper their use despite the clear symptomatic and disease modifying benefits. However, the evidence base for these concerns for low dose glucocorticoid therapy is quite limited due to the scarcity of quality literature on its safety in rheumatoid arthritis. This review discusses the current understanding about their disease-modifying effects, toxicity data from recent trials and observational studies, recommendations for their management and the current efforts to improve the therapeutic ratio of glucocorticoid through the development of new formulations, such as modified-release prednisone.
25973092 Roles of claudin-5 and von Willebrand factor in patients with rheumatoid arthritis. 2015 Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affects approximately 1% of the world's population. The pathogenesis of RA is not understood fully. It is assumed that endothelial function is associated with the proinflammatory state of RA. Endothelial dysfunction/activation reflects the increased level of von Willebrand factor (vWF) and a shift toward prothrombotic activity of the endothelium. The present study was performed to investigate the possible relationships between vWF and claudin-5 and the level of disease activity in patients with RA. The study population was divided into four groups according to the disease activity score in 28 joints (DAS28): remission group (RG), 18 patients (DAS28 < 2.6); low disease activity group (LDAG), 23 patients (DAS28 > 2.6-3.2); moderate disease activity (MDAG), 23 patients (DAS28 > 3.2-5.1); high disease activity group (HDAG), 14 patients (DAS28 > 5.1); and control group (CG), 10 healthy subjects. Claudin-5 and vWF assessment were derived from serum samples gathered from the patients known to have RF and anti-CCP titers in the normal ranges. A high positive association of claudin-5 and vWF with the MDAG was observed (P < 0.001). The results of our study indicated that the relationship between vWF and claudin-5, which are indicators of endothelial cell dysfunction and tight junction activity, may be a predictor of disease activity. Further studies are required to investigate these pathways to shed light on the roles of claudin-5 and vWF in the progression of inflammation and other vascular conditions.
27803965 The role of ultrasound in diagnosing rheumatoid arthritis, what do we know? An updated rev 2017 Feb To clarify if musculoskeletal ultrasound (MSUS) improves early diagnosis of RA when added to the clinical examination of patients with possible arthritis. We performed a systematic literature review of original studies dealing with the value of MSUS in the early diagnosis of RA. Studies were identified using the databases of PubMed, EMBASE and Cochrane library. Only studies in English investigating populations with non-classified arthritis or arthralgia were included. Fifteen original studies investigating the added value of MSUS in diagnosing RA were identified. They differed in sample size, study population, serology status, number of joints investigated and regarding the ultrasound machines and probes used. Thirteen out of 15 studies concluded that use of MSUS had an added value compared to clinical examination and laboratory evaluation alone for diagnosing RA. One study found that MSUS did not add substantial discriminatory value for predicting RA in an early arthritis cohort when added to routine assessment. However, in this study only 16 joints were examined (wrists and MTP 3-5 were not included). One study investigated only seropositive patients and found no significant advantage of MSUS on patient level although a trend was noted. Accordingly, two other studies found MSUS to be useful especially in seronegative patients. The use of MSUS adds value in diagnosing early RA, especially in seronegative arthritis. However, no study to date has documented any effect of DMARD initiation based on MSUS findings (subclinical arthritis) alone. More studies investigating this matter are warranted.
26989909 New concepts of clinical trials in rheumatoid arthritis: a boom of noninferiority trials. 2016 May PURPOSE OF REVIEW: The purpose is to describe the most recent randomized controlled trials (RCT) in patients with rheumatoid arthritis that had a noninferiority design, and to focus on methodological aspects of noninferiority. RECENT FINDINGS: In 2014 and 2015 10 different RCTs with a noninferiority-design could be identified, in comparison to only a few in the decade before. Most RCTs had a rather small sample size, and had ill-defined noninferiority-margins, or noninferiority-margins without comprehensible clinical meaning. Six of the 10 trials indeed arrived at a conclusion of 'noninferiority'; four did not. Interestingly, many of the RCTs were pragmatic studies comparing strategies, and the investigators were neither blind to the treatment nor to the outcome. In addition, the treatments were often adaptive (e.g. treat-to-target approach). These characteristics are considered built-in incentives for noninferiority. SUMMARY: In the competitive pharmaceutical landscape of rheumatoid arthritis, with many effective drugs and strategies, it is no surprise that the number of noninferiority-trial (sharply) rises. But noninferiority trials are difficult to design, conduct, and interpret, and many principles of noninferiority-trial designs are currently ignored, which may jeopardise their conclusions to some extent.
26915909 One-year maintenance with routine assessment of patient index data 3-based remission may i 2016 Nov OBJECTIVES: We investigated whether the maintenance of routine assessment of patient index data 3 (RAPID3) remission for one year (RAPID3-MR) may predict good radiographic outcomes. We also compared radiographic progression to prognostic factors among patients with RAPID3-MR, with the maintenance of clinical disease activity index remission for one year (CDAI-MR) or with the maintenance of 28 joint count disease activity score remission for one year (DAS28-MR). METHODS: Of 1220 patients with available clinical data, 92 with RAPID3-MR, 80 with RAPID3-NMR (not satisfying RAPID3-MR), 45 with CDAI-MR, and 75 with DAS28-MR were retrospectively investigated. CDAI and DAS28 for clinical outcomes and the modified total Sharp score (mTSS) for radiographic joint damage were investigated for at least one year. RESULTS: RAPID3, CDAI, DAS28, and their categories remained unchanged or significantly improved in RAPID3-MR patients but significantly deteriorated in RAPID3-NMR patients. The mean annual ΔmTSS was significantly lower in RAPID3-MR patients (0.12 ± 0.55) than in RAPID3-NMR patients (0.54 ± 1.27) (p = 0.025). There was no significant difference among RAPID3-MR patients, CDAI-MR patients (0.06 ± 0.85), and DAS28-MR patients (0.11 ± 0.89). The baseline mTSS (p = 0.038) and monotherapy with nonbiological disease-modifying antirheumatic drugs (p = 0.033) were good prognostic factors in RAPID3-MR patients. CONCLUSIONS: One-year RAPID3 remission maintenance may predict good radiographic outcomes.
26338656 A study on the effective substance of the Wu-tou formula based on the metabonomic method u 2015 Nov The Wu-tou formula (WTF) is a Chinese medicine formula which has been applied to treat rheumatic arthritis (RA) and pain of joints for more than a thousand years. In this study, a pharmacodynamics combined urinary metabonomic study using UPLC-Q-TOF-HDMS was performed to assess the holistic efficacy of the Traditional Chinese Medicine (TCM) Wu-tou formula for treating RA in rats. Eighty male Sprague-Dawley rats were randomly divided into eight groups, named as the healthy control group (HG), the model group (AIA), the WTF group and five single herb groups. The treatment groups and the model group were induced for treating rheumatoid arthritis by using complete Freund's adjuvant. Histological results assessed the joint damage and several biochemical parameters such as IL-1β, TNF-α, SOD and MDA were used to evaluate inflammation injury and oxidative stress. Based on the results, a metabonomic investigation was conducted to study the mechanism of the WTF and single herb treatment groups for treating RA. Multivariate statistical analyses such as PCA and OPLS-DA were used to identify potential biomarkers in urine. As a result, twenty-six potential biomarkers have been found by comparison with the model and the WTF treatment group. The potential biomarkers mainly affect the phenylalanine, tyrosine and tryptophan biosynthesis pathway and the taurine and hypotaurine metabolism pathway. Aconiti Radix Preparata and Ephedrae Herba showed better effects on treating RA from the integrated evaluation by histological results, biochemical parameters and pattern recognition analysis. A comprehensive evaluation of the different therapeutic effects and the mechanism of each herb in the WTF for treating RA was performed in this research.
25211403 Relationships between serum 25-hydroxycalciferol, vitamin D intake and disease activity in 2015 Mar OBJECTIVES: The effect of serum 25-hydroxycalciferol [25(OH)D] on rheumatoid arthritis (RA) activity remains controversial. This study was undertaken with an aim to clarify the relationship between serum 25(OH)D and RA activity, and to determine the effects of dietary vitamin D intake and age on serum 25(OH)D level. METHODS: A total of 208 outpatients with RA were matched according to age and sex with 205 individuals without RA (controls) from the TOMORROW study (UMIN000003876). We excluded 27 patients with RA and 19 control subjects who had been prescribed vitamin D medication or were taking vitamin D supplements. Vitamin D intake was assessed in the remaining 181 patients and 186 controls using the brief-type dietary history questionnaire. Serum 25(OH)D levels were measured using a radioimmunoassay. RESULTS: Serum 25(OH)D levels were significantly lower in patients with RA than in the controls (p < 0.001). There was a significant and positive correlation between age and 25(OH)D in the patients (r = 0.283, p < 0.001), as with vitamin D intake and 25(OH)D, even after adjusting for age (r = 0.313, p < 0.001). Disease activity and 25(OH)D did not significantly correlate. CONCLUSIONS: Patients with RA were observed to have serum 25(OH)D levels which correlated with vitamin D intake and age but not disease activity.
27402172 Neutropenia in the Elderly: A Rheumatology Perspective. 2016 Aug The majority of rheumatic diseases are chronic and require long-term use of disease-modifying agents to confer the best chance of controlling the disease. A significant proportion of these drugs have a risk, albeit small, of potentially serious side effects, such as neutropenia; therefore, there has been an understandable concern over the use of potentially toxic rheumatic drugs in the elderly. Factors that may contribute to this concern include age, pre-existing co-morbidities, polypharmacy, difficulty in monitoring side effects, and patient perception. The risk of using such medication needs to be balanced with their benefits in controlling chronic disease. This review discusses how rheumatic disease and anti-rheumatic medication are associated with neutropenia in an older age group. Of the rheumatic diseases, we give special focus to rheumatoid arthritis and the use of methotrexate, as well as touching on management considerations in neutropenia.
28606571 Effect of ω-3 polyunsaturated fatty acids on arthritic pain: A systematic review. 2017 Jul OBJECTIVES: Pain is a significant problem in rheumatoid arthritis (RA) and is associated with prostaglandins derived from the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid. The ω-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid have been shown to reduce inflammation, with some studies showing clinical improvements in RA. The aim of this systematic review was to investigate the effect of ω-3 PUFAs on arthritic pain. METHOD: A systematic literature review of ω-3 PUFAs and pain associated with RA was performed up to December 2015. Randomized controlled trials (RCTs) investigating the effect of ω-3 PUFAs (>2 g/d) on patient or physician assessment of pain, or assessment by both patient and physician, were included. The Cochrane Collaboration's tool for assessing risk for bias was employed. Data for outcomes of interest were extracted and collated for interpretation. RESULTS: Eighteen RCTs published between 1985 and 2013 involving 1143 patients were included. Dosage of ω-3 PUFAs used was 2.1 to 9.1 g/d, with study durations of 12 to 52 wk. Ten studies supported the hypothesis that there is a reduction in patient or physician assessment of pain associated with RA after intake of ω-3 PUFAs. Eight studies found no statistically significant effect of ω-3 PUFAs on arthritic pain. CONCLUSIONS: ω-3 PUFAs may have a therapeutic role in decreasing pain associated with RA, with doses of 3 to 6 g/d appearing to have a greater effect. Due to the limitations identified in the RCTs included in this review, more research is needed to investigate ω-3 PUFAs in larger populations and over extended periods of time.
28123118 Analysis of correlation and causes for discrepancy between quantitative and semi-quantitat 2017 Feb OBJECTIVES: The aim of this study was to evaluate the association between two semi-quantitative Doppler US scoring systems (SQS), and the quantitative scoring (QS) of Doppler pixel count. METHODS: Adult patients with RA and inadequate clinical response to anti-rheumatic therapy were examined with musculoskeletal US (MSUS). Dorsal MSUS of the wrists, MCP and MTP 2-5 were performed. MSUS images with sign of synovitis were collected and the QS was measured. Five assessors blinded to the QS evaluated the images independently, according to either SQS method. Association between QS and SQS was studied using correlations and multilevel models taking into account the clustering of ratings at the rater, patient and joint levels. RESULTS: Analysis of the 1190 ratings revealed a strong correlation (ρ = 0.89, P < 0.0001) and significant associations (P < 0.0001) between QS and SQS. Correlations between QS and SQS according to Szkudlarek et al. (ρ = 0.87, P < 0.0001) or Hammer et al. (ρ = 0.91, P < 0.0001) were similar. A total of 239 (20.1%) images were given a SQS grade that did not match that expected based on initial QS, using pre-defined cut-offs. Main explanations for discrepancies were different perceived region of interest (40.7%) and Doppler pixel count near cut-offs between SQS grades (32.3%). CONCLUSION: We showed that both SQS methods correlated well with QS to assess synovitis, but SQS methods are intrinsically limited when the Doppler pixel count is close to the cut-offs between the SQS grades. Analysis discrepancies between these methods may help further revision of criteria used to assess disease activity with MSUS in RA.
27341745 Safety of biologic DMARDs in RA patients in real life: A systematic literature review and 2017 Mar OBJECTIVES: In daily practice, safety in rheumatoid arthritis (RA) patients receiving biological treatment is an important issue. Unlike randomized controlled trials, biologic registers provide long-term real life safety data. To identify all biologic registers worldwide, to extract and analyze data regarding safety in RA patients under biologics. METHOD: Systematic review was performed independently by 2 rheumatologists using PUBMED, COCHRANE Library and EMBASE databases, up to December 2014. Worldwide biologic registers and related publications were identified. Data on safety issues in RA patients were extracted for meta-analyses. Random-effect meta-analyses were performed to estimate risk ratios (RRs) of mortality, cardiovascular events, cancer, including lymphoma and melanoma and serious infections between (1) biological and non-biological DMARD (cDMARD), (2) between biologics when data were available. RESULTS: Forty-three biological registers were identified worldwide and 27 publications were included for safety meta-analyses on anti-TNFs. Compared to cDMARD, mortality and cardiovascular events were significantly decreased in patients treated with anti-TNFs: RR=0.60 [95% CI 0.38-0.94] and RR=0.62 [0.44-0.88], respectively. Anti-TNFs did not increase the risk of solid cancer in patients without or with prior malignancy (RR=0.84 [0.60-1.18] and RR=0.77 [0.29-2.03], respectively), lymphoma (RR=0.90 [0.62-1.31]) and melanoma (RR=1.17 [0.86-1.59]). As expected, serious infections were significantly increased during anti-TNF treatment (RR=1.48 [1.18-1.85]) compared to cDMARD. No significant difference was found between soluble receptor to TNF and monoclonal antibodies (RR=0.55 [0.22-1.35]). CONCLUSIONS: By reducing dramatically chronic inflammation in RA patients, anti-TNFs decrease mortality, cardiovascular events without increase significantly the risk of cancer, compared to cDMARDs.
27623077 AAA-ATPase p97 suppresses apoptotic and autophagy-associated cell death in rheumatoid arth 2016 Sep 27 Valosin containing protein (p97) is a chaperone implicated in a large number of biological processes including endoplasmic reticulum (ER)-associated protein degradation and autophagy. Silencing of p97 in rheumatoid arthritis (RA) synovial fibroblasts (RASFs) increased the amount of polyubiquitinated proteins, whereas silencing of its interaction partner histone deacetylase 6 (HDAC6) had no effect. Furthermore, silencing of p97 in RASFs increased not only rates of apoptotic cell death induced by TRAIL but also induced an autophagy-associated cell death during ER stress that was accompanied by the formation of polyubiquitinated protein aggregates and large vacuoles. Finally, we demonstrated an anti-arthritic effect of siRNAs targeting p97 in collagen-induced arthritis in rats. Our data indicate that p97 may be a new potential target in the treatment of RA.
27017787 [Role of cytokines and their blocking in immune-mediated inflammatory diseases]. 2016 Rheumatoid arthritis, inflammatory bowel diseases and psoriasis are examples of immune-mediated inflammatory diseases. They involve activation of a partly similar cytokine network that has an essential role in the disease pathogenesis. Biological drugs have been developed for the inhibition of single cytokines, and good therapeutic responses have been achieved by using them. For instance, TNF blockers are used in the treatment of several inflammatory diseases. The use of the blockers of certain other cytokines is more limited. Other important target molecules include certain interleukins. New bispecific antibodies enabling inhibition of the action of two distinct cytokines are currently undergoing clinical studies.
27073832 In Patients with Established RA, Positive Effects of a Randomised Three Month WBV Therapy 2016 Functional ability is often impaired for people with rheumatoid arthritis (RA), rendering these patients highly sedentary. Additionally, patients with RA often take medication known to negatively affect bone mass. Thus improving functional ability and bone health in this group of patients is important. The aim of this study was to investigate the effects of whole body vibration (WBV) therapy in patients with stable, established RA. Thirty one females with RA were randomly assigned to a control group (CON, n = 15) who continued with their normal activities or a WBV group (n = 16) who underwent a three month WBV therapy intervention, consisting of 15 minutes of intermittent vibration, performed twice per week. Patients were assessed at baseline, three months, and three months post intervention for functional ability using the modified Health Assessment Questionnaire; for RA disease activity using the Clinical Disease Activity Index, for quality of life using self-report fatigue and pain scores; for physical activity profiles using accelerometry, and for BMD and body composition using DXA. Patients in both groups were matched for all variables at baseline. After the intervention period, functional ability was significantly improved in the WBV group (1.22(0.19) to 0.92(0.19), p = 0.02). Hip BMD was significantly reduced in the CON group (0.97(0.05) to 0.84(0.05) g.cm(-2), p = 0.01), while no decreases were seen in the WBV group (1.01(0.05) to 0.94(0.05) g.cm(-2), p = 0.50). Despite no change in RA disease activity in either group at either follow up, fatigue levels were improved in the WBV group (4.4(0.63) to 1.1(0.65), yet remained unchanged in the CON group at both follow ups (p = 0.01). Ten minute bouts of light to moderate physical activity were significantly reduced in the CON group after the intervention (2.8(0.61) to 1.8(0.64) bouts per day, p = 0.01), and were preserved in the WBV group (3.1(0.59) to 3.0(0.61) bouts per day, p = 0.70). Intermittent WBV shows promise for sustained improvements in functional ability, for attenuating loss of bone mass at the hip, as well as for decreasing fatigue in patients with established RA. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201405000823418.
26213309 Brief report: enhancement of patient recruitment in rheumatoid arthritis clinical trials u 2015 Nov OBJECTIVE: Rheumatoid arthritis (RA) clinical trials often exclude patients who have low C-reactive protein (CRP) levels, which slows enrollment into the trial. The purpose of this study was to determine whether high Multi-Biomarker Disease Activity (MBDA) scores (>44) in RA patients with low CRP levels (≤10 mg/liter) could be used as a complement to CRP levels >10 mg/liter to enhance patient recruitment without affecting clinical trial outcomes. METHODS: We evaluated patients from the Swedish Pharmacotherapy (SWEFOT) trial, which did not include any selection criteria for CRP levels. Clinical outcomes were assessed after 3 months of methotrexate (MTX) monotherapy in MTX-naive RA patients (n = 220) and after 3-10 months of add-on therapy in patients who were incomplete responders to MTX alone (MTX-IR) (n = 127). Radiographic outcomes were assessed at 1 year in all patients. Within each cohort, the outcomes were compared between patients with a CRP level of ≤10 mg/liter and an MBDA score of >44 at the start of the respective treatment interval versus those with a CRP level of >10 mg/liter. RESULTS: Patients with both a CRP level of ≤10 mg/liter and an MBDA score of >44 at baseline had clinical and radiographic outcomes that were comparable to those in patients with a CRP level of >10 mg/liter at baseline. This broadened definition of the inclusion criteria identified an additional 24% of patients in the MTX-naive cohort and 47% in the MTX-IR cohort. CONCLUSION: Patient recruitment into RA clinical trials may be substantially enhanced, without any decrease in clinical and radiographic outcomes, by using as an inclusion criterion "a CRP level of >10 mg/liter and/or an MBDA score of >44."
26289049 Evaluation of a disease specific rheumatoid arthritis self-management education program, a 2015 Aug 20 BACKGROUND: Rheumatoid Arthritis is a progressive and disabling disease, predicted to increase in prevalence over the next 50 years. Self-management is acknowledged as an integral part in the management of chronic disease. The rheumatoid arthritis specific self-management program delivered by health professionals was developed by Arthritis Western Australia in 2006. The purpose of this study was to determine whether this program would achieve early benefits in health related outcomes, and whether these improvements would be maintained for 12 months. METHODS: Individuals with rheumatoid arthritis were referred from rheumatologists. Participants with co-existing inflammatory musculoskeletal conditions were excluded. All participants completed a 6-week program. Assessments occurred at baseline (8 weeks prior to intervention), pre-intervention, post-intervention, and 6 and 12 month follow ups. Outcomes measured included pain and fatigue (numerical rating scale, 0-10), depression and anxiety (hospital anxiety and depression questionnaire), health distress, and quality of life (SF-36 version 2). RESULTS: There were significant improvements in mean [SD] fatigue (5.7 [2.4] to 5.1 [2.6]), depression (6.3 [4.3] to 5.6 [3.9]) and SF-36 mental health (44.5 [11.1] to 46.5 [9.5]) immediately following intervention, with long term benefits for depression (6.3 [4.3] to 4.9 [3.9]), and SF-36 subscales mental health (44.5 [11.1] to 47.8 [10.9]), role emotional (41.5 [13.2] to 46.5 [11.8]), role physical (35.0 [11.0] to 40.2 [12.1]) and physical function (34.8 [11.5] to 38.6 [10.7]). CONCLUSION: Participants in the program recorded significant improvements in depression and mental health post-intervention, which were maintained to 12 months follow up.
26865600 Antibodies to native and citrullinated RA33 (hnRNP A2/B1) challenge citrullination as the 2016 Nov BACKGROUND: Anti-citrullinated protein antibodies (ACPAs) are the hallmark of rheumatoid arthritis (RA). Protein citrullination is believed to drive autoantigen selection in RA. Nonetheless, several autoantigens in RA are targeted as native (unmodified) proteins. Here, the study of hnRNP A2/B1 (RA33) provides a framework to understand the humoral response to native and citrullinated autoantigens in RA. METHODS: RA synovial fluid (SF) cells were analysed by immunoblotting and mass spectrometry. RA33 was cloned from RASF cells and splice variants expressed as recombinant proteins. Antibodies against native and citrullinated RA33 were characterised by ELISA, immunoblotting and immunoprecipitation. RESULTS: RA33 is citrullinated in the rheumatoid joint and targeted either as a citrullinated or native protein in distinct patient subsets with RA. A novel splice variant (hnRNP B1b) previously associated with disease initiation in experimental arthritis was identified in the RA joint and acts as the major target of the anti-RA33 response. Antibodies exclusively targeting citrullinated RA33 were positively associated with disease duration and erosive disease. In contrast, anti-(native) RA33 antibodies were detected almost exclusively in early RA and identified patients with low radiographic erosion scores. Finally, a unique subset of double-reactive patients demonstrated intermediate severity, but rapid disease progression, suggesting a transitional disease phase in the evolution of an anti-native protein antibody to ACPA response in RA. CONCLUSIONS: These data suggest that native and citrullinated proteins targeted by autoantibodies in RA may be part of a single antibody system and challenge the paradigm of citrullination as the unifying principle underlying loss of tolerance in RA.
27025689 Development of a Functional Biomarker for Use in Cell-Based Therapy Studies in Seropositiv 2016 May Cell-based therapy has potential therapeutic value in autoimmune diseases such as rheumatoid arthritis (RA). In RA, reduction of disease activity has been associated with improvement in the function of regulatory T cells (Treg) and attenuated responses of proinflammatory effector T cells (Teff). Mesenchymal stem cells (MSCs) and related multipotent adult progenitor cells (MAPC) have strong anti-inflammatory and immunomodulatory properties and may be able to "reset" the immune system to a pre-RA state. MAPC are MSC-like cells that are slightly earlier in lineage, have greater expansion capacity, and can be used as "off-the-shelf" therapy. Assessment of cell-based therapy to treat arthritis and related diseases is limited by the lack of available biological correlates that can be measured early on and indicate treatment response. We set out to develop a functional measure that could be used ex vivo as a biomarker of response. We were able to demonstrate that MAPC products could inhibit Teff responses from patients with active RA and that Treg from RA patients suppressed Teff. This assay used ex vivo can be used with MAPC or Treg alone or in combination and reflects the overall level of Teff suppression. Use of a novel functional biomarker as an exploratory endpoint in trials of cell-based therapy should be of value to detect biological outcomes at a point prior to the time that clinical response might be observed. SIGNIFICANCE: Therapy with mesenchymal stem cells and related multipotent adult progenitor cells is immune modifying in a variety of diseases. There is interest in using cell-based therapy in rheumatoid arthritis (RA) to induce tolerance and "reset" the immune system to its pre-RA state. In a clinical trial, it should be known as soon as possible if there is a chance of response. A biomarker has been developed that permits measurement of the effects of cell-based therapy on effector T cell function.
25754335 Rheumatoid arthritis is sufficient to cause atheromatosis but not arterial stiffness or hy 2015 May Rheumatoid arthritis (RA) associates with increased cardiovascular disease (CVD) mortality thought to be due to accelerated arterial disease. Different components of arterial disease, namely, atheromatosis, arteriosclerosis, and arterial wall hypertrophy, are differentially affected by classical CVD risk factors, which are highly prevalent in these patients. We hypothesized that RA disease per se may also differentially affect these components. Of 267 consecutive RA patients, we selected specifically those who were free of established CVD and CVD risk factors (18 %); of them, 41 patients (36 women, 49 ± 13 years) could be matched effectively 1:1 for age and gender to healthy controls. Atheromatosis was assessed by the presence of carotid and/or femoral artery plaques, arteriosclerosis by pulse wave velocity and local wall elasticity, and arterial hypertrophy by intima-media thickness and cross-sectional area. More patients had atheromatic plaques than controls (29 vs. 12 %, p = 0.039), and multiarterial atheromatosis was more prevalent in RA (22 vs. 2 %, p = 0.026). Accelerated atheromatosis was not associated with rheumatoid factor, or anti-cyclic citrullinated peptide (CCP) autoantibody status. Plaque burden in patients with less than 5 years disease duration (aged 41 ± 13 years) was comparable to their matched controls. In contrast, all indices of arterial stiffness and hypertrophy were similar between controls and RA patients, even in those with long-standing disease. RA per se is sufficient to cause atheromatosis in the absence of classical CVD risk factors, but has minimal, if any, effect on arteriosclerosis and arterial wall hypertrophy.
25347362 Species cross-reactivity of rheumatoid factors and implications for immunoassays. 2015 Jan Rheumatoid factors (RFs) are antibodies recognizing other antibodies usually by binding to the Fc part, while heterophilic antibodies (HAbs) are antibodies reacting with immunoglobulins (Igs) from other species. In particular, RFs have been found to cause false positive results in sandwich immunoassays. In this work, we analyzed RF-positive and RF-negative sera for content of cytokines and for heterophilic reactions by enzyme-linked immunosorbent assay and bead-based sandwich immunoassays. All sera, including those with RFs, contained insignificant amounts of cytokines and chemokines, but RF-positive sera showed large false positive values for several cytokines when analyzed by fluorescent bead-based multiplex immunoassays. This non-specific binding could be minimized by reagents designed to block HAbs, i.e. by selected animal IgGs. Furthermore, sera positive for RFs reacted with several animal IgGs, when these were immobilized on beads or coated on the polystyrene surface in enzyme-linked immunosorbent assays. This reaction could be inhibited by human IgG and by agents designed to inhibit heterophilic reactions (i.e. mixtures of IgGs from different species). In conclusion, RFs and HAbs represent an identical/overlapping set of antibodies, causing false positive reactions in sandwich and other immunoassays. Such assays must be conducted in the presence of appropriate blocking agents, e.g. HBR+, and must be carefully controlled.