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ID PMID Title PublicationDate abstract
29949166 Effects of TNF-α in rheumatoid arthritis via attenuating α1 (I) collagen promoter. 2018 Jun OBJECTIVE: To explore the role of TNF-α in the peripheral blood of patients with rheumatoid arthritis (RA) and its underlying mechanism. PATIENTS AND METHODS: 32 patients diagnosed with RA in our hospital from July 2016 to March 2017 were selected in the experimental group. Meanwhile, 32 normal healthy people were selected in the healthy control group and 21 patients with other autoimmune diseases in the same period were selected in the disease control group. Serum samples of the subjects in the experimental group and the control group were collected. The content of serum tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA), and the correlation between TNF-α and RA activity was analyzed. We then constructed rat RA model. The effect of different doses of TNF-α on the RA progression was evaluated by measuring the foot paw thickness of both hind limbs of rats. Fibroblast-like synoviocytes (FLS) were treated with different concentrations of TNF-α cytokine in vitro. Cell counting kit-8 (CCK-8) assay was carried out to detect the cell viability after TNF-α treatment. Serum levels of VEGF (vascular endothelial growth factor) and hydroxyproline were detected. Moreover, the α1 (I) collagen overexpression recombinant was constructed and transfected into MH7A cells. The activation of α1 (I) collagen promoter was reflected by the CAT reporter gene activity. RESULTS: ELISA results showed higher content of TNF-α in the peripheral blood of the experimental group than that of the control group. In the RA rat model, the foot paw thickness of the hind limbs was increased with the increase of TNF-α concentration. CCK-8 and colony formation assay demonstrated that the proliferation of MH7A cells was elevated after TNF-α treatment. Higher levels of VEGF and IL-6 secreted by FLS and decreased collagen synthesis ability of MH7A cells were found after TNF-α treatment. Transfection of the α1 (I) collagen overexpression recombinant in MH7A cells led to the reduced activity of CAT after TNF-α treatment, suggesting that the activation of α1 (I) collagen promoter was inhibited. CONCLUSIONS: TNF-α participates in RA by inhibiting the activation of the promoter of α1 (I) collagen, as well as enhancing the secretion of VEGF and IL-6 in MH7A cells.
28893409 Equivalence in the Health Assessment Questionnaire (HAQ) across socio-demographic determin 2018 Feb OBJECTIVES: To investigate potential bias in scores of the Health Assessment Questionnaire (HAQ) related to socio-demographic (SD) background of patients with rheumatoid arthritis (RA). METHODS: Data from the Quantitative Standard Monitoring of Rheumatoid Arthritis study (QUEST-RA), comprising 9022 patients were analysed. Physical function was assessed through 30 items of four HAQ versions: the HAQ-Disability scale, HAQ-II, modified HAQ and multi-dimensional HAQ (MD-HAQ). DIF was investigated using item response theory models implemented in a latent variable modelling framework. Models were equivalent to ordinal logistic regression models with HAQ score (item level) as outcome, the latent trait 'physical function' and individual SD factors (age, gender, education, and employment status) as predictors. Next, scores of composite HAQs were adjusted for DIF. To assess the impact of DIF on associations between SD factors and HAQs, multilevel mixed-effect linear regression models with individuals nested in country were estimated with DIF-adjusted or unadjusted HAQ as outcome. RESULTS: Relevant DIF (OR > 1.1 or <0.90) was found in several HAQ items primarily for age, gender and work status. Adjustment of composite HAQs for DIF resulted in small increases (Δ0.02-0.07); MD-HAQ best compensated for bias related to SD factors (Δ0.02). In regressions, all SD factors remained significantly related to DIF-adjusted HAQs, with differences in coefficients largest for gender (Δ0.02-0.07) but overall negligible. CONCLUSIONS: SD factors produce response bias in individual HAQ items but have little impact on composite HAQs. When interpreting HAQ across SD factors, MD-HAQ is preferred, but caution remains when comparing function across gender.
30152847 Galangin protects human rheumatoid arthritis fibroblast‑like synoviocytes via suppressio 2018 Oct Rheumatoid arthritis (RA) is a chronic autoimmune disease that significantly affects patient quality of life. Galangin is an extract with multiple health benefits, including anti‑oxidative, anti‑proliferative, immunoprotective and cardioprotective effects. However, to the best of the authors' knowledge, no detailed studies have investigated its regulatory effects on the nuclear factor (NF)‑κB/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. The present study aimed to investigate the protective mechanism of galangin in RA fibroblast‑like synoviocytes with regards to the NF‑κB/NLRP3 signaling pathway. Human RA fibroblast‑like synovium cells (RAFSCs) were treated with lipopolysaccharide (LPS) to induce inflammation. The levels of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α, IL‑18, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, prostaglandin E2 (PGE2), and nitric oxide (NO) were measured by enzyme‑linked immunosorbent assay or western blotting in the absence or presence of different concentrations of galangin. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were additionally evaluated. Furthermore, factors involved in the NF‑κB/NLRP3 pathway, including NLRP3, apoptosis‑associated speck‑like protein containing A, IL‑1β, pro‑caspase‑1, caspase‑1, phosphorylated (p)‑NF‑κB inhibitor α and p‑NF‑κB, were assessed by western blotting. The results revealed that LPS significantly stimulated IL‑1β, TNF‑α, IL‑18, PGE2, NO, iNOS, COX‑2 and NF‑κB/NLRP3 factor expression, compared with the control. SOD activity was reduced. Pre‑treatment with galangin significantly attenuated the effects of LPS, and galangin was demonstrated to have effective anti‑oxidative properties. In conclusion, galangin protected RAFSCs through downregulation of the NF‑κB/NLRP3 signaling pathway. These findings suggested that galangin may provide a novel direction for the development of RA therapies in the future.
27315340 Serum and synovial fluid concentrations of cold-inducible RNA-binding protein in patients 2018 Jan AIM: There is growing evidence that cold-inducible RNA-binding protein (CIRP) promotes inflammatory responses. This study investigated the relationship between CIRP and rheumatoid arthritis (RA). METHODS: Peripheral blood and synovial fluid were collected from 15 patients with RA and from 16 patients with osteoarthritis (OA). The concentration of CIRP was measured with the sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of serum CIRP was significantly elevated in the RA patient group (RA patients = 26.39 ± 10.48 pg/mL, OA patients = 17.14 ± 7.24 pg/mL, P = 0.009). Furthermore, the RA patient group had a significantly higher CIRP concentration than that of the OA patient group in synovial fluid (153.56 ± 108.93 pg/mL vs. 23.63 ± 16.18 pg/mL, P < 0.001). The mean synovial fluid concentration of CIRP was significantly higher than that of the serum concentration in the RA patient group (serum concentration = 26.39 ± 10.48 pg/mL, synovial fluid = 153.56 ± 108.93 pg/mL, P < 0.001). Disease Activity Score of 28 joints (DAS28)-ESR (erythrocyte sedimentation rate) and DAS28-CRP (C-reactive protein) were positively correlated with the synovial fluid concentration of CIRP (DAS28-ESR: r = 0.582, P = 0.023; DAS28-CRP: r = 0.541, P = 0.037). CONCLUSION: The serum and synovial concentrations of CIRP in the RA patients were increased compared to the OA patients. Additionally, the synovial concentration of CIRP in RA patients correlated well with disease activity, that is, the DAS28-ESR/CRP. Based on these results, CIRP mediates inflammation and is a potential marker for synovial inflammation.
30047845 Novel tumor necrosis factor-α (TNF-α) inhibitors from small molecule library screening f 2019 Jun Tumor necrosis factor alpha (TNF-α) is a multifunctional cytokine that acts as a central biological mediator for critical immune functions, including inflammation, infection, and antitumor responses. It plays pivotal role in autoimmune diseases like rheumatoid arthritis (RA). The synthetic antibodies etanercept, infliximab, and adalimumab are approved drugs for the treatment of inflammatory diseases bind to TNF-α directly, preventing its association with the tumor necrosis factor receptor (TNFR). These biologics causes serious side effects such as triggering an autoimmune anti-antibody response or the weakening of the body's immune defenses. Therefore, alternative small-molecule based therapies for TNF-α inhibition is a hot topic both in academia and industry. Most of small-molecule inhibitors reported in the literature target TNF-α, indirectly. In this study, combined in silico approaches have been applied to better understand the important direct interactions between TNF-α and small inhibitors. Our effort executed with the extensive literature review to select the compounds that inhibit TNF-α. High-throughput structure-based and ligand-based virtual screening methods are applied to identify TNF-α inhibitors from 3 different small molecule databases (∼256.000 molecules from Otava drug-like green chemical collection, ∼ 500.000 molecules from Otava Tangible database, ∼2.500.000 Enamine small molecule database) and ∼240.000 molecules from ZINC natural products libraries. Moreover, therapeutic activity prediction, as well as pharmacokinetic and toxicity profiles are also investigated using MetaCore/MetaDrug platform which is based on a manually curated database of molecular interactions, molecular pathways, gene-disease associations, chemical metabolism and toxicity information, uses binary QSAR models. Particular therapeutic activity and toxic effect predictions are based on the ChemTree ability to correlate structural descriptors to that property using recursive partitioning algorithm. Molecular Dynamics (MD) simulations were also performed for selected hits to investigate their detailed structural and dynamical analysis beyond docking studies. As a result, at least one hit from each database were identified as novel TNF-α inhibitors after comprehensive virtual screening, multiple docking, e-Pharmacophore modeling (structure-based pharmacophore modeling), MD simulations, and MetaCore/MetaDrug analysis. Identified hits show predicted promising anti-arthritic activity and no toxicity. Communicated by Ramaswamy H. Sarma.
29017772 T cell activation Rho GTPase activating protein (TAGAP) is upregulated in clinical and exp 2018 Apr Genome-wide association studies have identified various susceptibility variants and loci associated with incidence of rheumatoid arthritis (RA) in different populations. One of these is T cell activation Rho GTPase activating protein (TAGAP). The present study sought to measure the expression of TAGAP in RA patients, CD4(+) T cells subsets from healthy humans and in mice with collagen-induced arthritis. Peripheral blood mononuclear cells (PBMC) from RA patients and tissues of arthritic mice at different stages of the disease were used for the evaluation of TAGAP mRNA expression. Increased TAGAP expression was observed in RA patients compared to healthy controls, and there were differences in the expression level of TAGAP in the tissues of mice with experimental arthritis. Gene expression in CD4(+) T cells from healthy humans was greatest 4 h after activation and protein expression was greatest after 24 h. The expression of TAGAP was not correlated with CD4(+) lymphocyte subsets which were enriched for functionally defined subsets (Th17, Treg, Th1), further indicating its utility as an indicator of lymphocyte activation. These findings indicate that increased TAGAP expression is a distinguishing feature of inflammatory disease and further highlight the role of TAGAP in RA susceptibility.
29566213 Long-term persistence with rituximab in patients with rheumatoid arthritis. 2018 Jun 1 OBJECTIVES: To investigate the long term persistence of rituximab (RTX) in a large observational RA cohort, investigate persistence of RTX when used as a first or second line biologic DMARD (bDMARD), to characterize subsequent bDMARD treatment following RTX. METHODS: Patients with RA starting treatment with RTX (MabThera) between 2008 and 2011 were recruited into the British Society for Rheumatology Biologics Register for RA. Duration of RTX treatment over the first 4 years after initiation was estimated via Kaplan-Meier estimates and the reason for discontinuation was ascertained. Subsequent bDMARD use following RTX discontinuation was characterised. Treatment survival in bDMARD-naïve (first line RTX use) and experienced (second line RTX use) cohorts was described. RESULTS: One thousand six hundred and twenty-nine patients were recruited (1371 bDMARD-experienced and 258 bDMARD-naïve). Sixty percent of the whole cohort remained on RTX after 4 years. Ineffectiveness (46%) and death (24%) were the most common reason for RTX discontinuation. RTX discontinuation was associated with RF negativity for the bDMARD-experienced cohort. Of those that discontinued RTX, 46% initiated treatment with another bDMARD, with tocilizumab being the most common. CONCLUSION: This large study of patients initiating RTX treatment for severe RA found that 60% persisted with treatment after 4 years. This study also identified that RTX is tolerated well when used as a first or second line bDMARD.
29298709 Testing the construct validity of a health transition question using vignette-guided patie 2018 Jan 3 BACKGROUND: A single-item transition question is often used to assess improvement or worsening in health, but its validity has not been tested extensively. The purpose of this study was to test the construct validity of a transition question by relating it to qualitative changes in patient's self-rating of health guided by clinical vignettes. METHODS: We studied 169 patients with active rheumatoid arthritis (RA) before and after treatment escalation. At both assessments, patients scored their current health on a rating scale after first rating three vignettes describing mild, moderate, or severe RA. We classified patients into one of these three RA categories using a nearest-neighbor match. We then related the change in these self-rated categories between visits to responses to a transition question on visit 2. RESULTS: Sixty patients improved their RA vignette category after treatment, 86 remained in the same vignette category, and 23 worsened categories. On the transition question, 101 patients reported improvement, 48 reported no change, and 20 reported worsening, representing a modest association with changes in RA vignette categories (polychoric correlation r = 0.19). The association was stronger if patients who were in the mild RA category at both visits were also classified as improved if their self-rating changed from below to above their mild vignette rating (r = 0.23) and when incorporating the importance of changes on the transition question (r = 0.26). CONCLUSION: Changes in health states, guided by clinical vignettes, support the construct validity of the transition question.
30215901 Rheumatologic Tests: A Primer for Family Physicians. 2018 Aug 1 Patients with a suspected connective tissue disorder should undergo serologic testing to confirm the diagnosis and, in some cases, to monitor disease activity and predict flares. Patients with suspected systemic lupus erythematosus should be tested for antinuclear antibodies. However, antinuclear antibodies are not specific and may be present in many other connective tissue disorders and nonrheumatologic diseases. Thus, patients with suspected systemic lupus erythematosus should undergo further testing to confirm the diagnosis. Patients with Sjögren syndrome may have a positive antinuclear antibody titer, but often also have positive anti-Sjögren antigen A or B results. Similarly, antinuclear antibodies can be present in patients with scleroderma, mixed connective tissue disease, and dermatomyositis or polymyositis. Additional tests are needed to help confirm the diagnosis. In patients with findings of rheumatoid arthritis, a positive rheumatoid factor titer suggests the diagnosis, but as with antinuclear antibodies, it is not specific and can occur in other conditions. Rheumatoid factor can also be negative in patients with rheumatoid arthritis. A positive anticyclic citrullinated peptide antibody titer is more specific for rheumatoid arthritis and can help confirm the diagnosis. Physicians should order these serologic tests only when patients have a high pretest probability of a specific connective tissue disorder.
29414640 Malondialdehyde-acetaldehyde antibody concentrations in rheumatoid arthritis and other rhe 2018 Mar OBJECTIVE: To compare anti-malondialdehyde-acetaldehyde (MAA) antibody concentrations between rheumatoid arthritis (RA) patients and healthy and rheumatic disease controls. METHODS: Anti-MAA antibody (IgA, IgM, IgG) was measured using ELISA and banked serum from patients with RA (n = 284), osteoarthritis (OA, n = 330), spondyloarthropathy (SpA, n = 50), and systemic lupus erythematosus (SLE, n = 88) as well as healthy controls (n = 82). Anti-MAA antibody concentrations and the frequency of positivity were compared across groups. Multivariable linear regression analysis limited to RA and OA patients (due to sample size and data availability) was used to identify factors associated with anti-MAA antibody concentrations. RESULTS: Although RA patients demonstrated among the highest circulating concentrations across isotypes, only IgA anti-MAA antibody was significantly higher than all other groups (p ≤ 0.02). Proportions (7% to 74%) of OA and SLE (less so for SpA) samples were positive for anti-MAA antibody, limiting the discriminatory capacity of anti-MAA antibody in RA (positive in 18% to 80%). In analyses limited to those with RA or OA, factors associated with higher anti-MAA antibody concentrations included RA case status, younger age (IgM), male sex (IgG), African American race (IgA, IgG) and current smoking (IgA). C-reactive protein levels and comorbidities were not associated with anti-MAA antibody concentrations. CONCLUSION: With the possible exception of the IgA isotype, serum anti-MAA antibodies measured with currently available assays do not appear to adequately discriminate RA from other rheumatic conditions. With the identification of specific proteins that are MAA-modified in diseased tissues and requisite assay refinement, anti-MAA antibody holds potential promise as a biomarker in RA.
28963582 The 3'-UTR (CA)n microsatellite on CD40LG gene as a possible genetic marker for rheumatoid 2018 Feb The objective of this study was to determine the association of the CD40LG 3'-UTR (CA)n microsatellite with rheumatoid arthritis (RA) and CD40LG mRNA levels in females from western Mexico. A case-control study with 219 RA patients and 175 control subjects (CS) was conducted. Genotyping was performed by polymerase chain reaction (PCR), X (2) test was used to compare genotype and allele frequencies, and odds ratios and 95% confidence intervals were calculated to evaluate the association between RA and the microsatellite. CD40LG mRNA expression was assessed by real-time quantitative PCR. For comparisons between groups, Kruskal-Wallis or Mann-Whitney U tests for non-parametric data and ANOVA test for parametric data were performed. Among the 13 different alleles identified, CA(25) was the most represented (45.4% RA and 46.3% CS). Stratification according to CA repeats as CA(25) showed a tendency towards a higher frequency of >CA(25) alleles in RA patients (29%) compared to CS (23.4%). There was no association between any genotype and the clinical parameters of RA patients. According to the 2(-∆∆Cq) method, CD40LG mRNA expression in RA patients was 4.5-fold higher compared to CS; this difference was significant when assessed by the 2(-∆Cq) method (p = 0.028). Compared to carriers of the CA(25)/CA(25) genotype, CS carrying the CA(25)/>CA(25) carriers. The 3'-UTR CD40LG (CA)n microsatellite is not a genetic marker for RA in western Mexican population; however, results suggest that it plays a role in the CD40LG mRNA expression.
30283452 Redox-Mediated Mechanisms Fuel Monocyte Responses to CXCL12/HMGB1 in Active Rheumatoid Art 2018 Chemokine synergy-inducing molecules are emerging as regulating factors in cell migration. The alarmin HMGB1, in its reduced form, can complex with CXCL12 enhancing its activity on monocytes via the chemokine receptor CXCR4, while the form containing a disulfide bond, by binding to TLR2 or TLR4, initiates a cascade of events leading to production of cytokines and chemokines. So far, the possibility that the CXCL12/HMGB1 heterocomplex could be maintained in chronic inflammation was debated, due to the release of reactive oxygen species. Therefore, we have assessed if the heterocomplex could remain active in Rheumatoid Arthritis (RA) and its relevance in the disease assessment. Monocytes from RA patients with active disease require a low concentration of HMGB1 to enhance CXCL12-induced migration, in comparison to monocytes from patients in clinical remission or healthy donors. The activity of the heterocomplex depends on disease activity, on the COX2 and JAK/STAT pathways, and is determined by the redox potential of the microenvironment. In RA, the presence of an active thioredoxin system correlates with the enhanced cell migration, and with the presence of the heterocomplex in the synovial fluid. The present study highlights how, in an unbalanced microenvironment, the activity of the thioredoxin system plays a crucial role in sustaining inflammation. Prostaglandin E2 stimulation of monocytes from healthy donors is sufficient to recapitulate the response observed in patients with active RA. The activation of mechanisms counteracting the oxidative stress in the extracellular compartment preserves HMGB1 in its reduced form, and contributes to fuel the influx of inflammatory cells. Targeting the heterocomplex formation and its activity could thus be an additional tool for dampening the inflammation sustained by cell recruitment, for those patients with chronic inflammatory conditions who poorly respond to current therapies.
29422900 Role of SLC7A5 in Metabolic Reprogramming of Human Monocyte/Macrophage Immune Responses. 2018 Amino acids (AAs) are necessary nutrients which act not only as building blocks in protein synthesis but also in crucial anabolic cellular signaling pathways. It has been demonstrated that SLC7A5 is a critical transporter that mediates uptake of several essential amino acids in highly proliferative tumors and activated T cells. However, the dynamics and relevance of SLC7A5 activity in monocytes/macrophages is still poorly understood. We provide evidence that SLC7A5-mediated leucine influx contributes to pro-inflammatory cytokine production via mTOR complex 1 (mTORC1)-induced glycolytic reprograming in activated human monocytes/macrophages. Moreover, expression of SLC7A5 is significantly elevated in monocytes derived from patients with rheumatoid arthritis (RA), a chronic inflammatory disease, and was also markedly induced by LPS stimulation of both monocytes and macrophages from healthy individuals. Further, pharmacological blockade or silencing of SLC7A5 led to a significant reduction of IL-1β downstream of leucine-mediated mTORC1 activation. Inhibition of SLC7A5-mediated leucine influx was linked to downregulation of glycolytic metabolism as evidenced by the decreased extracellular acidification rate, suggesting a regulatory role for this molecule in glycolytic reprograming. Furthermore, the expression of SLC7A5 on circulating monocytes from RA patients positively correlated with clinical parameters, suggesting that SLC7A5-mediated AA influx is related to inflammatory conditions.
29408488 Regulation and function of apoptosis signal-regulating kinase 1 in rheumatoid arthritis. 2018 May Despite improved therapy, rheumatoid arthritis (RA) remains an unmet medical need. Previous efforts to validate therapeutic targets in the mitogen-activated protein kinase (MAPK) family have had minimal success. Therefore, we evaluated the potential for targeting an upstream MAPK, namely apoptosis signal-regulating kinase 1 (ASK1), as an alternative approach. ASK1 protein and gene expression were observed in RA and osteoarthritis (OA) synovium as determined by immunohistochemistry (IHC) and qPCR, respectively, particularly in the synovial intimal lining. For RA, but not OA synovium, ASK1 correlated with IL-1β and TNF gene expression. ASK1 was also expressed by cultured fibroblast-like synoviocytes (FLS), with significantly higher levels in RA compared with OA cells. IL-1β and TNF stimulation significantly increased ASK1 expression in a time-and concentration-dependent manner in cultured FLS. ASK1 promoter activity was significantly increased by IL-1β and TNF and was dependent on an upstream RelA binding motif. A selective small molecule ASK1 inhibitor reduced RA FLS invasion, migration and proliferation in vitro and decreased arthritis severity in the rat collagen-induced arthritis (CIA) model. In summary, our findings demonstrate that ASK1 modulates signaling pathways relevant to RA in vitro and in vivo. It is induced by inflammatory cytokines through the activation of NF-κB, which could provide some site- and event specificity. Thus, inhibitors of the upstream MAPK ASK1 could be a novel approach to treating inflammatory arthritis.
30062448 The relationship between bristol rheumatoid arthritis fatigue scales and disease activity 2018 Nov Fatigue is a symptom that affects the 40-80% of patients with rheumatoid arthritis (RA) and impairs the quality of life. The aim of this study was to assess multidimensional fatigue scales, the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) and the Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scale (BRAF-NRS) and to evaluate their relationship with disease activity in Turkish RA patients. The study included 180 patients with RA. The Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) were used to evaluate disease activity. The participants comprised of 142 females and 38 males. The mean ± standard deviations of DAS28, CDAI, and SDAI were 3 ± 1.24, 9.51 ± 7.96, and 10.5 ± 8.38 respectively. All scales except the emotional subscale were correlated with disease activity. The emotional subscale correlated with CDAI and SDAI but not with DAS28. The results of the study indicated that fatigue and disease activity were correlated. Fatigue is a symptom that impairs the quality of life but it can be easily coped with by controlling disease activity. Thus, it should be assessed in a multidimensional perspective.
28871338 Comparison of the effectiveness on intra-articular and subcutaneous TNF inhibitor in rheum 2018 Jan The objective of this study is to evaluate the efficacy of single intra-articular (IA) injection of tumor necrosis factor α (TNFα) inhibitor in knee joints comparing with subcutaneous injection in rheumatoid arthritis (RA) patients. Forty-eight RA patients with 73 knee arthritis were divided into three groups, group A: received a single injection of TNF inhibitor into knee joints; group B: received regular subcutaneous injection; and group C: received both of the regimen as groups A and B. Ultrasound, erythrocyte sedimentation rate, C-reactive protein (CRP), patients' global visual analogue scale (VAS), and 28-joint Disease Activity Score (DAS28) were collected pre- and post-therapy 4 weeks. The results of the study are as follows: (1) CRP, VAS, and DAS28 of all groups improved significantly post-therapy (p < 0.05); (2) After therapy, synovial hypertrophy (SH) decreased significantly from 4.40 ± 1.86 mm to 2.74 ± 1.88 mm (p < 0.05) and power Doppler (PD) signal decreased significantly from 2.63 ± 0.75 to 1.50 ± 0.93 (p < 0.01) in group A. Synovial effusion (SE), SH, and PD showed no significant improvement in group B. SE decreased significantly from 9.84 ± 4.70 mm to 5.89 ± 4.47 mm (p < 0.05), SH decreased significantly from 4.52 ± 1.97 mm to 2.49 ± 1.73 mm (p < 0.01), and PD decreased significantly from 2.46 ± 0.66 to 1.38 ± 1.04 (p < 0.01) in group C; and (3) The improvement rate of SH and PD in both groups A and C was obviously higher than that of group B (p < 0.05). Single IA injection of TNFα inhibitor was an effective treatment in improvement of SH and PD of knee joints than subcutaneous injection in RA patients.
30204634 Exercise for Athletes With Inflammatory Arthritis. 2018 Sep Advances in pharmacologic management of inflammatory conditions have allowed those living with these conditions to pursue fitness activities previously difficult due to functional limitations. With that said, many patients with inflammatory arthritis are still not active enough. In this article, we review specific exercise recommendations for a number of inflammatory conditions with a focus on overall health promotion and cardiovascular disease risk reduction, discuss exercise as an adjunct to pharmacologic disease management, and review potential risks of sport participation for athletes with inflammatory arthritis conditions.
29148413 Variable impacts of different remission states on health-related quality of life in rheuma 2018 Mar OBJECTIVES: Targeting remission in rheumatoid arthritis (RA) improves health-related quality of life (HRQoL) and disability. However, the impacts of different remission criteria and durations and their frequencies are uncertain. Our observational study assessed these factors. METHODS: We recruited RA patients with disease durations <10 years, stable suppressive therapies and stable disease activity scores for 28 joints using ESR (DAS28-ESR) ≤3.2. Intermittent and sustained remisisons were classified using DAS28ESR, simple disease activity index (SDAI) and ACR/EULAR Boolean criteria. HRQoL, measured using SF-36, fatigue, EuroQol and health assessment questionnaire (HAQ) was compared using time-integrated areas under the curve (AUC). RESULTS: 104 patients were enrolled and followed for 12 months. DAS28-ESR remissions were intermittent in 42%, sustained in 47% and absent in 11%. Boolean remissions were intermittent in 38%, sustained in 10% and absent in 52%. Baseline remissions by all criteria significantly improved HAQ, Euroqol, SF36 and fatigue scores compared with low disease activity (LDAS); AUCs showed significant benefits for all HRQoLs persisted over 12-months. Boolean remissions achieved most benefits. Over time all remission states gave significantly better HRQoL scores than LDAS. Sustained DAS28ESR and SDAI remissions improved HRQoL more than intermittent remissions. Sustained and intermittent Boolean remissions gave similar improvements. Analysis of SF-36 domains showed even sustained Boolean remissions failed to optimise pain and fatigue. CONCLUSIONS: All remissions improve HRQoL but different criteria have variable impacts. Boolean remission had most impact but occurred least. There are trade-off between optimising individual impacts (Boolean remissions) and achieving maximal overall impacts (DAS28-ESR remissions).
29449496 Patient-reported Outcomes, Resource Use, and Social Participation of Patients with Rheumat 2018 Jun OBJECTIVE: To characterize patient-reported outcomes, resource use, and social participation during the course of biologic therapy for indigenous and non-indigenous patients with rheumatoid arthritis (RA). METHODS: Patients initiating biologic therapy (2004 to 2012) were characterized longitudinally for patient-reported outcomes including physical function measured by the Health Assessment Questionnaire, EQ-5D, well-being [Medical Outcomes Study Short Form-36 (SF-36)], and visual analog scales for pain, fatigue, sleep, stiffness, and patient's global assessment. Resource use, participation in activities of daily living, and effect of RA on work productivity were also evaluated for change during therapy. RESULTS: Indigenous patients (n = 90) presented with significantly worse scores for global evaluation, pain, sleep, quality of life, well-being, and physical function compared to non-indigenous patients (n = 1400). All patient-reported outcomes improved significantly during treatment for patients in both groups, but pain, sleep, and SF-36 physical health score changes occurred at slower rates for indigenous patients [difference in slopes 0.09 (p = 0.029), 0.08 (p = 0.043), and -0.35 (p = 0.03), respectively]. Performance of daily activities was affected for 50% of indigenous compared to 37% of non-indigenous patients, with more use of community services and assistance from others. Employed indigenous patients reported twice the number of days being unable to work owing to RA compared to employed non-indigenous patients. Of the unemployed indigenous patients, 82% indicated they had stopped working because of arthritis, versus 48% of non-indigenous patients (p < 0.0001). CONCLUSIONS: Indigenous patients have greater consequences of RA regarding experienced symptoms, health-related quality of life, disruption of performance of activities of daily living, and reduced employment participation.
30374344 Alpha2beta1 Integrin (VLA-2) Protects Activated Human Effector T Cells From Methotrexate-I 2018 β1 integrins are critical for T cell migration, survival and costimulation. The integrin α2β1, which is a receptor for collagen, also named VLA-2, is a major costimulatory pathway of effector T cells and has been implicated in arthritis pathogenesis. Herein, we have examined its ability to promote methotrexate (MTX) resistance by enhancing effector T cells survival. Our results show that attachment of anti-CD3-activated human polarized Th17 cells to collagen but not to fibronectin or laminin led to a significant reduction of MTX-induced apoptosis. The anti-CD3+collagen-rescued cells still produce significant amounts of IL-17 and IFNγ upon their reactivation indicating that their inflammatory nature is preserved. Mechanistically, we found that the prosurvival role of anti-CD3+collagen involves activation of the MTX transporter ABCC1 (ATP Binding Cassette subfamily C Member 1). Finally, the protective effect of collagen/α2β1 integrin on MTX-induced apoptosis also occurs in memory CD4(+) T cells isolated from rheumatoid arthritis (RA) patients suggesting its clinical relevance. Together these results show that α2β1 integrin promotes MTX resistance of effector T cells, and suggest that it could contribute to the development of MTX resistance that is seen in RA.