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ID PMID Title PublicationDate abstract
26051464 2014 update of the Consensus Statement of the Spanish Society of Rheumatology on the use o 2015 Sep OBJECTIVE: To establish recommendations for the management of patients with rheumatoid arthritis (RA) to serve as a reference for all health professionals involved in the care of these patients, and focusing on the role of available synthetic and biologic disease-modifying antirheumatic drugs (DMARDs). METHODS: Consensual recommendations were agreed on by a panel of 14 experts selected by the Spanish Society of Rheumatology (SER). The available scientific evidence was collected by updating three systematic reviews (SR) used for the EULAR 2013 recommendations. A new SR was added to answer an additional question. The literature review of the scientific evidence was made by the SER reviewer's group. The level of evidence and the degree of recommendation was classified according to the Oxford Centre for Evidence-Based Medicine system. A Delphi panel was used to evaluate the level of agreement between panellists (strength of recommendation). RESULTS: Thirteen recommendations for the management of adult RA were emitted. The therapeutic objective should be to treat patients in the early phases of the disease with the aim of achieving clinical remission, with methotrexate playing a central role in the therapeutic strategy of RA as the reference synthetic DMARD. Indications for biologic DMARDs were updated and the concept of the optimization of biologicals was introduced. CONCLUSIONS: We present the fifth update of the SER recommendations for the management of RA with synthetic and biologic DMARDs.
27283483 Preclinical efficacy of a gastro-sparing novel thiazolidin-4-one in alleviating secondary 2016 Aug 25 The promising role of thiazolidin-4-ones (TZOs) against inflammatory conditions has been reported. From our lab, one of the TZO derivatives, compound 4C, exerted anti-inflammatory potential via inhibition of locally released cytokines and prostaglandin. In continuance, a detailed study was undertaken for the preclinical profiling of this promising TZO derivative against polyarthritis in rats, along with assessment of risk associated with the treatment. Male Sprague-Dawley rats were used for the adjuvant-induced arthritis (AIA) model. Based on the development of secondary lesion, the animals were randomized into different treatment groups. To establish the efficacy of the test compound, parameters such as inflammation, pain, disease progression, cytokines and prostaglandin (PG)-E2 levels and complete blood cell profile were recorded along with radiological and histological examinations of joints. The study also focused on evaluating the side effect of test compound on gastric, liver, renal, blood and cardiovascular components. Compound 4C exerted promising therapeutic effect against secondary lesions in polyarthritis in rats. It limited the progression of chronic inflammation and associated pain in rats. Modulation of cytokine signalling and arachidonate metabolism by 4C was evident from inhibition of interleukin (IL)-6, tumor necrosis factor (TNF)-α and PGE2 generation in AIA rats. Comparatively, compound 4C was safer than diclofenac to cause gastric, liver, renal, blood and cardiovascular toxicities. These finding supports the efficacy and safety profile of 4C, a TZO derivative in limiting the progression of arthritis when administered orally.
27816728 Triptolide inhibits the migration and invasion of rheumatoid fibroblast-like synoviocytes 2016 Dec Triptolide, a primary active ingredient extracted from a traditional Chinese herb, Tripterygium wilfordii Hook F, has been demonstrated to have a positive therapeutic effect on patients with rheumatoid arthritis (RA); however, its mechanism of action against RA is not well established. Therefore, in the present study, we observed the effect of triptolide on the aggressive behavior of RA fibroblast-like synoviocytes (RA FLSs), and we explored its underlying signal mechanisms. We found that triptolide treatment significantly reduced the migratory and invasive capacities of RA FLSs in vitro. We also demonstrated that the invasion of RA FLSs into the cartilage, evaluated in the severe combined immunodeficiency (SCID) mouse co-implantation model, was attenuated by treatment with triptolide in vivo. Additionally, the immunofluorescence results showed that triptolide treatment decreased the polymerization of F-actin and the activation of matrix metalloproteinase 9 (MMP-9). To gain insight into the molecular signal mechanisms, we determined the effect of triptolide on the activation of MAPK signal pathways. Our results indicate that triptolide treatment reduced the TNF-α-induced expression of phosphorylated JNK, but did not affect the expression of phosphorylated p38 and ERK. A JNK-specific inhibitor decreased the migration of RA FLSs. We also observed that triptolide administration improved clinical arthritic conditions and joint destruction in mice with collagen-induced arthritis (CIA). Thus, our findings suggest that the therapeutic effects of triptolide on RA might be, in part, due to its contribution to the aggressive behavior of RA FLSs.
26064930 Influence of Immunogenicity on the Efficacy of Long-Term Treatment with TNF α Blockers in 2015 OBJECTIVE: To analyze the clinical relevance of the levels of TNFα blockers and anti-drug antibodies (anti-drug Ab) in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) for a prolonged period of time. METHODS: Clinical characteristics (disease activity, and adverse events), serum TNFα blockers, and anti-drug Ab levels were evaluated in 62 RA and 81 SpA patients treated with TNFα blockers for a median of 28 months. RESULTS: Anti-ADA Ab were detected in 1 (4.0%) and anti-INF Ab in 14 out of 57 (24.6%) RA and SpA patients. Patient with anti-ADA Ab and 57.1% patients with anti-INF Ab were considered nonresponders to treatment. Anti-ETA Ab were not found in any of 61 ETA treated patients. Anti-ADA and anti-INF Ab levels differ between responders and nonresponders (P > 0.05). Three (5.3%) patients with high serum anti-INF Ab levels developed infusion related reactions. Patients with anti-INF Ab more often required changing to another biologic drug (OR 11.43 (95% CI 1.08-120.93)) and treatment discontinuation (OR 9.28 (95% CI 1.64-52.52)). CONCLUSION: Patients not responding to treatment had higher serum anti-ADA and anti-INF Ab concentrations. Anti-INF Ab formation is related to increased risk of infusion related reactions, changing to another biologic drug, and treatment discontinuation.
25219368 Expression and function of aminopeptidase N/CD13 produced by fibroblast-like synoviocytes 2015 Jan OBJECTIVE: Aminopeptidase N/CD13 (EC 3.4.11.2) is a metalloproteinase expressed by fibroblast-like synoviocytes (FLS). It has been suggested that CD13 can act chemotactically for T cells in rheumatoid arthritis (RA). We undertook this study to measure CD13 in vivo and in vitro in RA samples and to determine whether CD13 could play a role in the homing of T cells to the RA joint. METHODS: Interleukin-17-treated FLS were used to immunize mice, from which a novel anti-human CD13 monoclonal antibody (mAb), 591.1D7.34, was developed. The mAb 591.1D7.34 and a second anti-CD13 mAb, WM15, were used to develop a novel enzyme-linked immunosorbent assay (ELISA) for CD13, and CD13 enzymatic activity was measured in parallel. Chemotaxis of cytokine-activated T cells was measured by a chemotaxis-under-agarose assay. RESULTS: We detected substantial amounts of CD13 in synovial fluid (SF), sera, FLS lysates, and culture supernatants by ELISA, with a significant increase in CD13 in RA SF when compared to osteoarthritis SF. CD13 accounted for most but not all of the CD13-like enzymatic activity in SF. Recombinant human CD13 was chemotactic for cytokine-activated T cells through a G protein-coupled receptor and contributed to the chemotactic properties of SF independently of enzymatic activity. CONCLUSION: CD13 is released from FLS into culture supernatants and is found in SF. CD13 induces chemotaxis of cytokine-activated T cells, a T cell population similar to that found in RA synovium. These data suggest that CD13 could play an important role as a T cell chemoattractant, in a positive feedback loop that contributes to RA synovitis.
26752645 Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus. 2016 Feb The immunoregulatory cytokine macrophage migration inhibitory factor (MIF) is encoded in a functionally polymorphic locus that is linked to the susceptibility of autoimmune and infectious diseases. The MIF promoter contains a 4-nucleotide microsatellite polymorphism (-794 CATT) that repeats 5 to 8 times in the locus, with greater numbers of repeats associated with higher mRNA levels. Because there is no information about the transcriptional regulation of these common alleles, we used oligonucleotide affinity chromatography and liquid chromatography-mass spectrometry to identify nuclear proteins that interact with the -794 CATT5-8 site. An analysis of monocyte nuclear lysates revealed that the transcription factor ICBP90 (also known as UHRF1) is the major protein interacting with the MIF microsatellite. We found that ICBP90 is essential for MIF transcription from monocytes/macrophages, B and T lymphocytes, and synovial fibroblasts, and TLR-induced MIF transcription is regulated in an ICBP90- and -794 CATT5-8 length-dependent manner. Whole-genome transcription analysis of ICBP90 shRNA-treated rheumatoid synoviocytes uncovered a subset of proinflammatory and immune response genes that overlapped with those regulated by MIF shRNA. In addition, the expression levels of ICBP90 and MIF were correlated in joint synovia from patients with rheumatoid arthritis. These findings identify ICBP90 as a key regulator of MIF transcription and provide functional insight into the regulation of the polymorphic MIF locus.
25140583 Herpes Simplex Keratitis in Rheumatoid Arthritis Patients. 2016 Jun PURPOSE: To describe a series of 5 patients with herpes simplex virus keratitis (HSK) and rheumatoid arthritis (RA) under immunosuppressive treatment. METHODS: Retrospective study. Detailed data were obtained regarding symptoms and signs at the initial evaluation, treatment, microbiological diagnostic tests, evolution, and outcomes. RESULTS: Five patients with HSK and RA were identified. Bilateral involvement occurred in 2 patients (40%). Epithelial keratitis was diagnosed in 5 eyes. Three eyes showed severe melting with eye perforation. Gram-positive bacterial co-infections were common in the group with stromal keratitis. We did not find differences in the evolution of the disease based on anti-rheumatoid treatment. CONCLUSIONS: The characteristics of HSK in patients with RA differed from HSK in immunocompetent patients. The stromal keratitis cases were very aggressive and difficult to manage, with perforation and gram-positive bacterial co-infection as frequently associated conditions. Prophylactic therapy at standard doses was unsuccessful to avoid recurrences.
25853482 A comparison of disease burden in rheumatoid arthritis, psoriatic arthritis and axial spon 2015 OBJECTIVE: The main objective of this study was to compare disease burden in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA). METHODS: In this cross-sectional study, all the RA (1093), PsA (365) and ax-SpA (333) patients who visited the out-patient clinic of the Hospital of Southern Norway Trust during the year 2013 were included; the RA patients all had a RA diagnosis verified by the treating rheumatologist, the PsA patients all fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria and the ax-SpA patients all fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for ax-SpA. Patient-reported health status, demographic variables, medications, and composite scores of disease activity were assessed. The main analyses were performed using General Linear Models adjusted for age, sex and multiple comparisons. Correlation analyses were performed using Spearman's rho. RESULTS: The reported pain, joint pain, patient's global assessment and fatigue were similar in PsA and ax-SpA, but significantly lower in RA. The 28-joint Disease Activity Score (DAS28) (0.3±0.1, p = 0.003), Clinical Disease Activity Index (CDAI) (1.0±0.4, p = 0.028) and Routine Assessment of Patient Index Data 3 (RAPID3) (0.4±0.1, p = 0.004) were all significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation with DAS28 (rho = 0.521, p<0.001) and CDAI (rho = 0.768, p<0.001) in RA and PsA, and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (rho = 0.902, p<0.001) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.865, p<0.001) in ax-SpA and PsA. CONCLUSION: In conclusion, patient- reported outcome measures were similar in our population of PsA and ax-SpA patients, but significantly lower for the RA patients. Composite disease activity measures were lower in RA than in PsA and ax-SpA, but the magnitude of these differences was small and probably not of clinical significance. Our study indicates that disease burden in RA, PsA and ax-SpA may be more similar than previously demonstrated.
27822475 RANK Expression and Osteoclastogenesis in Human Monocytes in Peripheral Blood from Rheumat 2016 Rheumatoid arthritis (RA) appears as inflammation of synovial tissue and joint destruction. Receptor activator of NF-κB (RANK) is a member of the TNF receptor superfamily and a receptor for the RANK ligand (RANKL). In this study, we examined the expression of RANK(high) and CCR6 on CD14(+) monocytes from patients with RA and healthy volunteers. Peripheral blood samples were obtained from both the RA patients and the healthy volunteers. Osteoclastogenesis from monocytes was induced by RANKL and M-CSF in vitro. To study the expression of RANK(high) and CCR6 on CD14(+) monocytes, two-color flow cytometry was performed. Levels of expression of RANK on monocytes were significantly correlated with the level of osteoclastogenesis in the healthy volunteers. The expression of RANK(high) on CD14(+) monocyte in RA patients without treatment was elevated and that in those receiving treatment was decreased. In addition, the high-level expression of RANK on CD14(+) monocytes was correlated with the high-level expression of CCR6 in healthy volunteers. Monocytes expressing both RANK and CCR6 differentiate into osteoclasts. The expression of CD14(+)RANK(high) in untreated RA patients was elevated. RANK and CCR6 expressed on monocytes may be novel targets for the regulation of bone resorption in RA and osteoporosis.
26748745 Emerging therapy in arthritis: Modulation of markers of the inflammatory process. 2016 Feb The induction of tolerance has been proposed as a therapeutic strategy for arthritis aiming to decrease progression of the pathology, probably by promoting suppressor mechanisms of the autoimmune response. This work aimed to confirm whether the treatment with vitamin D3 could synergize oral tolerance induced by hydrolyzed collagen peptides, in our experimental model of antigen induced arthritis in New Zealand rabbits. Clinical observation of the phenomenon indicates that simultaneous treatment with hydrolyzed collagen peptides and vitamin D3 was beneficial when compared with no treatment, for arthritic animals, and for arthritic animals that received treatment with only hydrolyzed collagen peptides or vitamin D3. Treatment with hydrolyzed collagen peptides caused diminished proinflammatory cytokine levels, an effect synergized significantly by the simultaneous treatment with vitamin D3. The anatomical-pathological studies of the animals that received both treatments simultaneously showed synovial tissues without lymphocytic and plasma cell infiltrates, and without vascular proliferation. Some of the synovial tissue of the animals of these groups showed a slight decrease in Galectin-3 expression. We propose that simultaneous oral treatment with vitamin D3 and hydrolyzed collagen peptides could increase the immunoregulatory effect on the process of previously triggered arthritis. We used articular cartilage hydrolysate and not collagen II because peptides best expose antigenic determinants that could induce oral tolerance. Oral tolerance may be considered in the design of novel alternative therapies for autoimmune disease and we have herein presented novel evidence that the simultaneous treatment with vitamin D3 may synergize this beneficial effect.
26418168 Total Saponin from Anemone flaccida Fr. Schmidt Prevents Bone Destruction in Experimental 2015 Dec Anemone flaccida Fr. Schmidt is used in the clinical compound prescription for the treatment of rheumatoid arthritis (RA) in China and has the traditional use of draining dampness, diminishing swelling, and relieving pain. Total saponins (TS) are the characteristic components and also the main active ingredients of A. flaccida. Previous reports indicated that TS possess anti-inflammatory and immunoregulatory properties; however, the effects of TS on bone destruction of RA have not been evaluated. In this study, our data first showed the therapeutic effects of TS on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) rats. Then, by microfocal computed tomography (CT) quantification, TS significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints both at peri-articular and extra-articular locations. TS also diminished the level of the bone resorption marker CTX-I and simultaneously increased the bone formation marker osteocalcin in sera of CIA rats. Interestingly, TS prevented bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of nuclear factor-κF (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. This was further confirmed in the co-culture system of human fibroblast-like synovial and peripheral blood mononuclear cells. In addition, TS inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNFα), IL-6, IL-17, and IL-23 in sera and joints. These findings offer convincing evidence that TS attenuate RA partially by preventing both focal bone destruction and systemic bone loss. This anti-erosive effect results in part from inhibiting osteoclastogenesis by regulating the RANKL/RANK/OPG signaling pathway. The suppression of systemic and local pro-osteoclastogenic cytokines by TS was also highly effective.
26055925 Toll-like receptor 2 (TLR2) induces migration and invasive mechanisms in rheumatoid arthri 2015 Jun 9 INTRODUCTION: This study investigates the role of Toll-like receptor 2 (TLR2) in the regulation of migratory and invasive mechanisms in rheumatoid arthritis (RA). METHODS: Invasion, migration, matrix metalloproteinase (MMP)-1, -3 and tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) expression, β-integrin binding, cytoskeletal rearrangement and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation in response to a TLR2-ligand, Pam3CSK4 (1 μg/ml), in ex vivo RA synovial tissue explants, primary RA synovial fibroblasts (RASFC) and microvascular endothelial cells (HMVEC) were assessed by Transwell Matrigel™ invasion chambers, enzyme-linked immunosorbent assay (ELISA), multiplex adhesion binding assay, reverse transcription polymerase chain reaction (RT-PCR), F-actin immunofluorescent staining, matrigel synovial outgrowths, Rac1 pull-down assays/Western blot and zymography. β1-integrin expression in RA/control synovial tissue was assessed by immunohistology. The effect of Pam3CSK4 on cell migration, invasion, MMP-3 and Rac1 activation was examined in the presence or absence of anti-β1-integrin (10 μg/ml) or anti-IgG control (10 μg/ml). The effect of an anti-TLR-2 mAb (OPN301)(1 μg/ml) or immunoglobulin G (IgG) control (1 μg/ml) on RASFC migration and RA synovial tissue MMP activity was assessed by wound assays, ELISA and zymography. RESULTS: Pam3CSK4 significantly induced cell migration, invasion, MMP-1, MMP-3, MMP-2 and MMP-9 expression and induced the MMP-1/TIMP-3 and MMP-3/TIMP-3 ratio in RASFC and explants (p <0.05). β1-integrin expression was significantly higher in RA synovial tissue compared to controls (p <0.05). Pam3CSK4 specifically induced β1-integrin binding in RASFC (p <0.05), with no effect observed for β2-4, β6, αvβ5 or α5β1. Pam3CSK4 increased β1-integrin mRNA expression, Rac1 activation, RASFC outgrowths and altered cytoskeletal dynamic through induction of filopodia formation. Pam3CSK4-regulated cell migration and invasion processes, but not MMP-3, were inhibited in the presence of anti-β1-integrin (p <0.05), with no effect observed for anti-IgG control. Furthermore, anti-β1-integrin inhibited Pam3CSK4-induced Rac1 activation. Finally, blockade of TLR2 with OPN301 significantly decreased spontaneous release of MMP-3, MMP-2 and MMP-9 and increased TIMP-3 secretion from RA synovial explant cultures (p <0.05). Incubation of RASFC with OPN301 RA ex vivo conditioned media inhibited migration and invasion compared to IgG control. CONCLUSIONS: TLR2 activation induces migrational and invasive mechanisms, which are critically involved in the pathogenesis of RA, suggesting TLR2 as a potential therapeutic target for the treatment of RA.
26071279 Multidrug resistance 1 (MDR1) 3435C>T gene polymorphism influences the clinical phenotype 2015 Aug PURPOSE: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily targeting the synovial joints causing joint damage and significant functional impairment. Methotrexate (MTX) remains the mainstay for the treatment of RA, and approximately 10-30% of the patients fail to attain remission because of inefficacy of the drug or due to development of adverse events. Multidrug resistance 1 (MDR1) gene encodes for permeable glycoprotein (P-gp) which is an integral membrane protein for the transport of chemotherapeutic agents, immunosuppressive drugs etc. MDR1 3435C>T results in a wobble mutation in exon 26 but is associated with altered P-gp expression and reduced P-gp function. The present study was carried out to find the role of MDR1 3435C>T gene polymorphism with clinical phenotype, treatment response, and MTX adverse events in 336 RA and 329 healthy controls of South Indian Tamil ethnicity. METHODS: MDR1 3435C>T gene polymorphism was analyzed by TaqMan 5' nuclease assay. RESULTS: We found MDR1 3435T allele as a risk allele for contributing to high EULAR disease activity [p = 0.02, OR 1.50, 95% CI (1.06-2.13)]. Also, MDR1 3435CT genotype was associated with deforming disease [p = 0.02, OR 1.79, 95% CI (1.11-2.88)]. However, this SNP did not influence the MTX treatment response in these patients. MDR1 3435CT genotype was associated with MTX-induced adverse events [p = 0.01, OR 2.01, 95% CI (1.15-3.52)], and the 3435 TT genotype remained protective for the development of adverse events [p = 0.009, OR 0.40, 95% CI (0.21-0.78)]. Also, the heterozygous 3435 CT genotype was associated with gastrointestinal events [p = 0.02, OR 3.62, 95% CI (1.25-10.47)], and CT genotype remained protective in patients developing infection [p = 0.002, OR 0.05, 95% CI (0.006-0.460)]. CONCLUSION: MDR1 3435C>T gene polymorphism influences the clinical phenotype and adverse events to MTX in the South Indian cohort of patients with RA.
26839159 Extracutaneous intravascular histiocytosis of the aortic valve: Report of two cases. 2016 Apr Intravascular histiocytosis (IVH) is a rare condition of uncertain pathogenesis often associated with rheumatoid arthritis (RA) exclusively observed in the skin. In a retrospective study of 207 consecutive cases of aortic valve disease, we observed two cases of IVH characterized by the presence of thin-walled, dilated blood vessels containing collections of CD68+ and CD163+ mononuclear histiocytes. Immunostains for CD31, CD34, and D2-40 confirmed the intravascular location of these histiocytes. One of the two cases was associated with RA. This case was observed among 41 cases of RA with calcific aortic valve stenosis. The other case was detected among 152 cases of calcific aortic valve stenosis in isolation. A total of 14 valves showed no calcification. IVH can manifest in the aortic valve and be associated with systemic disease. In contrast to other cases, the vessels observed in this study exhibited negative expression of the lymphatic marker D2-40. Our findings expand on the previously described location features of IVH.
25572319 The Swedish Exercise Self-Efficacy Scale (ESES-S): reliability and validity in a rheumatoi 2015 PURPOSE: The aim of the present study was to investigate aspects of reliability and validity of the Exercise Self-Efficacy Scale (ESES-S) in a rheumatoid arthritis (RA) population. METHODS: A total of 244 people with RA participating in a physical activity study were included. The six-item ESES-S, exploring confidence in performing exercise, was assessed for test-retest reliability over 4-6 months, and for internal consistency. Construct validity investigated correlation with similar and other constructs. RESULTS: An intraclass correlation coefficient (ICC) of 0.59 (95% CI 0.37-0.73) was found for 84 participants with stable health perceptions between measurement occasions. Cronbach's alpha coefficients of 0.87 and 0.89 were found at the first and second measurements. Corrected item-total correlation single ESES-S items ranged between 0.53 and 0.73. Construct convergent validity for the ESES-S was partly confirmed by correlations with health-enhancing physical activity and outcome expectations respectively (Pearson's r = 0.18, p < 0.01). Construct divergent validity was confirmed by the absence of correlations with age or gender. No floor or ceiling effects were found for ESES-S. CONCLUSIONS: The results indicate that the ESES-S has moderate test-retest reliability and respectable internal consistency in people with RA. Construct validity was partially supported in the present sample. Further research on construct validity of the ESES-S is recommended. IMPLICATIONS FOR REHABILITATION: Physical exercise is crucial for management of symptoms and co-morbidity in rheumatoid arthritis. Self-efficacy for exercise is important to address in rehabilitation as it regulates exercise motivation and behavior. Measurement properties of self-efficacy scales need to be assessed in specific populations and different languages.
25366699 Correlations between patient satisfaction and ability to perform daily activities after to 2015 Jan BACKGROUND: Patient satisfaction has become an important parameter for assessing overall outcomes after total knee arthroplasty (TKA). The level of difficulty in performing activities of daily life that affects overall patient satisfaction is unknown. We therefore evaluated the influence of difficulty in performing activities of daily life on patient satisfaction and expectations. METHODS: The 2011 Knee Society Knee Scoring System Questionnaire was mailed to patients who had undergone TKA with 375 patients completing and returning it. We evaluated the relationship between the ability to perform daily activities, as assessed via the questionnaire, and patient satisfaction and expectations of the same score in each patient using linear regression analysis. We also determined which activities affected patient satisfaction and expectations using multivariate linear regression analyses. RESULTS: All patient-derived functional activities correlated significantly with the patient satisfaction score. In particular, "climbing up or down a flight of stairs" followed by "getting into or out of a car," "moving laterally (stepping to the side)" and "walking and standing" correlated strongly with patient satisfaction by linear regression analysis and were revealed to have significant contributions to patient satisfaction by multivariate linear regression analysis. Regarding expectations, all patient-derived functional activities correlated significantly with the patient expectation score, although none of the correlation coefficients was very high. "Squatting," followed by "walking and standing," contributed to the patient expectation score by multivariate linear regression analysis. CONCLUSION: Activities related to walking and standing are some of the most basic movements and basic demands for patients. In addition, "climbing up or down a flight of stairs," "getting into and out of a car" and "squatting" are very important and distressing activities that significantly correlate with patient satisfaction after TKA.
26554018 Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis. 2015 Nov 24 Copy number variations (CNVs) have been implicated in human diseases. However, it remains unclear how they affect immune dysfunction and autoimmune diseases, including rheumatoid arthritis (RA). Here, we identified a novel leukocyte-specific protein 1 (LSP1) deletion variant for RA susceptibility located in 11p15.5. We replicated that the copy number of LSP1 gene is significantly lower in patients with RA, which correlates positively with LSP1 protein expression levels. Differentially expressed genes in Lsp1-deficient primary T cells represent cell motility and immune and cytokine responses. Functional assays demonstrated that LSP1, induced by T-cell receptor activation, negatively regulates T-cell migration by reducing ERK activation in vitro. In mice with T-cell-dependent chronic inflammation, loss of Lsp1 promotes migration of T cells into the target tissues as well as draining lymph nodes, exacerbating disease severity. Moreover, patients with RA show diminished expression of LSP1 in peripheral T cells with increased migratory capacity, suggesting that the defect in LSP1 signaling lowers the threshold for T-cell activation. To our knowledge, our work is the first to demonstrate how CNVs result in immune dysfunction and a disease phenotype. Particularly, our data highlight the importance of LSP1 CNVs and LSP1 insufficiency in the pathogenesis of RA and provide previously unidentified insights into the mechanisms underlying T-cell migration toward the inflamed synovium in RA.
25288785 Homing of mesenchymal stem cells: mechanistic or stochastic? Implications for targeted del 2015 Feb Mesenchymal stem cells (MSCs) are multipotent cells with the capacity to undergo chondrogenic differentiation. Systemically administered MSCs have been shown to preferentially accumulate at sites of tissue damage and inflammation, thus MSC-based therapy holds great promise for the treatment of inflammatory diseases such as RA. Modulation of MSC homing may allow targeted delivery of systemically administered MSCs to damaged articular cartilage, where they can suppress immune-mediated cartilage destruction and contribute to cartilage repair via a combination of chondrogenic differentiation and paracrine stimulation of intrinsic residual repair. To harness the potential of MSC homing, a thorough understanding of the mechanism is key. This review discusses current knowledge of the mechanism of MSC homing to injured/inflamed tissue and its implications for targeted MSC-based therapy in arthritis.
26190704 Rheumatoid arthritis-celiac disease relationship: joints get that gut feeling. 2015 Nov Rheumatoid arthritis (RA) and celiac disease (CD) belong to the autoimmune disease family. Despite being separate entities they share multiple aspects. Epidemiologically they share comparable incidence environmental influences, associated antibodies and a recent incidental surge. They differ in their HLA pre-dispositions and specific predictive and diagnostic biomarkers. At the clinical level, celiac disease exhibits extra-intestinal rheumatic manifestations and RA gastrointestinal ones. Small bowel pathology exists in rheumatic patients. A trend towards responsiveness to a gluten free diet has been observed, ameliorating celiac rheumatic manifestations, whereas dietary interventions for rheumatoid arthritis remain controversial. Pathophysiologically, both diseases are mediated by endogenous enzymes in the target organs. The infectious, dysbiotic and increased intestinal permeability theories, as drivers of the autoimmune cascade, apply to both diseases. Contrary to their specific HLA pre-disposition, the diseases share multiple non-HLA loci. Those genes are crucial for activation and regulation of adaptive and innate immunity. Recently, light was shed on the interaction between host genetics and microbiota composition in relation to CD and RA susceptibility, connecting bugs and us and autoimmunity. A better understanding of the above mentioned similarities in the gut-joint inter-relationship, may elucidate additional facets in the mosaic of autoimmunity, relating CD to RA.
26955672 [Treatment of Rheumatoid Arthritis by Hebi Recipe: an Efficacy Observation]. 2016 Jan OBJECTIVE: To observe the auxiliary efficacy and safety of Hebi Recipe (HR)in treating early rheumatoid arthritis (RA). METHODS: Totally 63 early RA patients with Gan-Pi disharmony were randomly assigned to the treatment group [32 cases, treated by HR (one dose per day, taken in two portions for 24 successive weeks) plus Methotrexate (MTX)] and the control group (31 cases, treated by MTX alone). The dosage of MTX was increased from 7.5 mg to 12.5 mg, once per week, 24 weeks as one course of treatment. Efficacy for Chinese medical syndromes, American College of Rheumatology 20 (ACR20) improvement rate, disease activity score in 28 joints (DAS28), laboratory related indices [ESR, rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP)], and related ultrasonic inspection items (synovium thickness, synovium blood flow classification, effusion of joint), and adverse reactions were observed. RESULTS: The total effective rate (83.9%, 26/31 cases) and ACR20 improvement rate (74.2%, 23/31 cases) were higher in the treatment group than in the control group [60.7% (17/28 cases), 46.4% (13/28 cases); P < 0.05]. Compared with before treatment in the same group, DAS28 score, ESR, RF, CRP, CCP, synovium thickness, synovium blood flow classification, effusion of joint all decreased in the two groups after treatment (P < 0.01, P < 0.05). Compared with the control group after treatment, ACR20 improvement rate, DAS28 score, ESR, RF, CRP, CCP, synovium thickness, synovium blood flow classification, effusion of joint all decreased in the treatment group (P < 0.01, P < 0.05). Liver dysfunction occurred in 1 case of the treatment group. One leucopenia and 2 liver dysfunction occurred in the control group. CONCLUSION: HR could effectively improve joints and systemic symptoms of early RA patients with Gan-Pi disharmony.