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ID PMID Title PublicationDate abstract
27133762 GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheuma 2016 Dec OBJECTIVES: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Fibroblast-like synoviocytes (FLS) in RA exhibit a tumor cell-like aggressive phenotype. Thus, gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS) was employed to identify the characteristic metabolic profiling of RA FLS. METHODS: Metabolite profiling of RA FLS and osteoarthritis (OA) FLS was performed using GC/TOF-MS in conjunction with statistical analyses. We performed metabolite set enrichment analysis to establish which pathways are affected. RESULTS: A total of 129 metabolites were identified. A principal component analysis and hierarchical clustering analysis demonstrated clear differentiation of the metabolic profiling between RA FLS and OA FLS. The levels of 35 metabolites that belonged to the amines, fatty acids, phosphates, and organic acids class were significantly increased in RA FLS compared to those in OA FLS. Also, the levels of 26 metabolites that belonged to the amino acids, sugars, and sugar alcohols class were significantly decreased in RA FLS compared to those in OA FLS. The sugar metabolism (glycolysis and pentose phosphate pathway) and amino acid metabolism (tyrosine and catecholamine biosynthesis, and protein biosynthesis) were severely disturbed in RA FLS compared to those in OA FLS. CONCLUSIONS: Our metabolic results suggested that the alteration of sugar metabolism, lipolysis, and amino acid metabolism in RA FLS is related to synovial hyperplasia and inflammation. This is the first metabolomic study to determine metabolic changes characteristic of RA FLS, which will provide valuable information to gain in-depth insights into the pathogenesis of RA.
24962872 Relationship between radiographic joint space narrowing, sonographic cartilage thickness a 2015 Nov OBJECTIVE: To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing (JSN) or width (JSW) in patients with rheumatoid arthritis (RA). METHODS: Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2-5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2-5 joints (n=19) were evaluated by anatomical measurement and US. RESULTS: The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=-0.32, p<0.001) and individual MCP JSW (r=0.72, p<0.001). No correlation was found between phalangeal cartilage thickness and JSN in individual MCP joints. The US MCT summary score for MCP joints 2-5 correlated with summary scores for JSW (r=0.78, p<0.001), JSN (r=-0.5, p<0.001), erosion score of the vdHS (r=-0.39, p<0.001) and total vdHS (r=-0.47, p<0.001). CONCLUSIONS: Sonographic cartilage assessment in MCPs is closely related to anatomical cartilage thickness. Both JSW and JSN by radiography represent cartilage thickness in the MCP joints of patients with RA quite well. Thus, US is a valid tool for measuring MCT if radiographs are not available or in case of joint malalignment.
27211565 Autonomic Dysfunction Precedes Development of Rheumatoid Arthritis: A Prospective Cohort S 2016 Apr BACKGROUND: Heart rate variability (HRV) is a validated method to establish autonomic nervous system (ANS) activity. Rheumatoid arthritis (RA) is accompanied by ANS imbalance. We hypothesized that ANS dysfunction may precede the development of RA, which would suggest that it plays a role in its etiopathogenesis. METHODS: First, we assessed HRV parameters in supine (resting) and upright (active) position in healthy subjects (HS, n=20), individuals at risk of developing arthritis (AR subjects, n=50) and RA patients (RA, n=20). Next, we measured resting heart rate (RHR), a parasympathetic HRV parameter, in an independent prospective cohort of AR subjects (n=45). We also evaluated expression levels of the parasympathetic nicotinic acetylcholine receptor type 7 (α7nAChR) on circulating monocytes. FINDINGS: Both AR subjects (68 beats per minute (bpm), interquartile range (IQR) 68-73) and RA patients (68bpm, IQR 62-76) had a significantly higher RHR compared to HS (60bpm, IQR 56-63). RHR was significantly higher at baseline in individuals who subsequently developed arthritis. Expression levels of α7nAChR were lower in AR subjects with RHR ≥70bpm compared to those with RHR <70bpm, consistent with reduced activity of the parasympathetic cholinergic anti-inflammatory pathway. INTERPRETATION: These data support the notion that autonomic dysfunction precedes the development of RA.
26513306 Agreement of Physicians and Nurses Performing Tender and Swollen Joint Counts in Rheumatoi 2016 Jan OBJECTIVE: The aims of this study were to assess the agreement of physicians and nurses performing tender and swollen joint counts (TJCs/SJCs) in rheumatoid arthritis (RA) and identify factors that might influence their examinations including patient age, sex, race, RA disease duration, body mass index, RA disease activity level, comorbid fibromyalgia, comorbid osteoarthritis, and levels of acute-phase reactants. METHODS: Seventy-two RA participants underwent TJCs/SJCs of 28 joints using a standardized protocol by 2 nurses and 2 rheumatologists. Demographic, laboratory, radiographic, and clinical data were obtained to assess the influence of these factors on TJCs/SJCs. Intraclass correlations (ICCs) among examiners were determined for TJCs/SJCs. Nurse-physician differences and agreement of individual joints were evaluated using Cohen κ. Analysis of variance was performed to detect differences in means between examiners for TJCs/SJCs. Intraclass correlation and Fisher Z tests were used to identify factors influencing TJCs/SJCs. RESULTS: Agreement was strong among these nurses and physicians for total TJCs/SJCs (ICC = 0.84/ICC = 0.79, respectively). κ was best for hand joint tenderness and poorest for shoulder swelling. Some significant differences in mean TJCs/SJCs were found between examiners. Fibromyalgia significantly reduced agreement of both TJCs and SJCs. Agreement of TJC was significantly reduced when patients had lower disease activity, greater work impairment, lower mental health quality of life, and elevated erythrocyte sedimentation rate, whereas female sex, assessor's perception of but not radiographic hand osteoarthritis, and elevated C-reactive protein significantly reduced agreement for SJC. CONCLUSIONS: Strong agreement was found among nurses and physicians for total 28-joint counts, with agreement at individual joints being stronger for tenderness than swelling. Fibromyalgia significantly reduced ICCs of TJCs/SJCs.
25488101 Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions 2015 Apr PURPOSE: To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. METHODS AND MATERIALS: Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. RESULTS: The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). CONCLUSION: The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods.
26178275 Development of Cardiovascular Quality Indicators for Rheumatoid Arthritis: Results from an 2015 Sep OBJECTIVE: Patients with rheumatoid arthritis (RA) have a high risk of premature cardiovascular disease (CVD). We developed CVD quality indicators (QI) for screening and use in rheumatology clinics. METHODS: A systematic review was conducted of the literature on CVD risk reduction in RA and the general population. Based on the best practices identified from this review, a draft set of 12 candidate QI were presented to a Canadian panel of rheumatologists and cardiologists (n = 6) from 3 academic centers to achieve consensus on the QI specifications. The resulting 11 QI were then evaluated by an online modified-Delphi panel of multidisciplinary health professionals and patients (n = 43) to determine their relevance, validity, and feasibility in 3 rounds of online voting and threaded discussion using a modified RAND/University of California, Los Angeles Appropriateness Methodology. RESULTS: Response rates for the online panel were 86%. All 11 QI were rated as highly relevant, valid, and feasible (median rating ≥ 7 on a 1-9 scale), with no significant disagreement. The final QI set addresses the following themes: communication to primary care about increased CV risk in RA; CV risk assessment; defining smoking status and providing cessation counseling; screening and addressing hypertension, dyslipidemia, and diabetes; exercise recommendations; body mass index screening and lifestyle counseling; minimizing corticosteroid use; and communicating to patients at high risk of CVD about the risks/benefits of nonsteroidal antiinflammatory drugs. CONCLUSION: Eleven QI for CVD care in patients with RA have been developed and are rated as highly relevant, valid, and feasible by an international multidisciplinary panel.
26087630 [Cerebrovascular reactivity in patients with rheumatoid arthritis concurrent with and with 2015 AIM: To compare cerebrovascular reactivity (CVR) in patients with rheumatoid arthritis (RA) concurrent with essential hypertension (Group 1) and in those with RA and normal blood pressure (BP) (Group 2). SUBJECTS AND METHODS: During the study of Groups 1 (n = 37) and 2 (n = 12), the investigators estimated the prevalence of traditional cardiovascular risk factors, performed 24-hour BP monitoring, investigated CVR by transcranial Doppler (TCD) of the middle cerebral arteries (MCA) by hyperoxic and hypercapnic tests, and endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation of the brachial artery. The groups were matched for gender, age, RA activity and stage, and antirheumatic therapy volume. RESULTS: According to the results of MCA TCD, the hyperoxic test recorded impaired CVR in 34 (92%) and 10 (83%) patients in Group 1 and 2, respectively; the hypercapnic test revealed this condition in 19 (51%) and 6 (50%) patients in these groups, respectively. The hyperoxic test most commonly showed an insufficient decrease in MCA linear blood flow velocities (LBFV) in 31 (84%) and 8 (66%) patients in Groups 1 and 2, respectively; the hypercapnic test did an excessive increase in MCA LBFV in 12 (32%) and 4 (33%) patients, respectively. There was a high rate of impaired EDV in 32 (86%) and 9 (75%) patients in Groups 1 and 2, respectively. CONCLUSION: According to the results of MCA TCD, there were high and similar rates of impaired CVR in patients with RA concurrent with and without essential hypertension during the hyperoxic and hypercapnic tests.
25857584 Oxidative stress in patients with rheumatoid arthritis. 2015 Jan BACKGROUND: Rheumatoid arthritis is an autoimmune disease of unknown etiology, characterized by articular inflammation. Oxidative damage induced by reactive oxygen species has been related to the pathophysiology of rheumatoid arthritis in several studies, although results have been inconsistent and contradictory. OBJECTIVE: To determine oxidative stress markers in patients with rheumatoid arthritis. METHODS: Descriptive cross-sectional study in rheumatoid arthritis patients and healthy controls. In peripheral blood samples from all study subjects, lipid peroxide (thiobarbituric acid reactive substances) and protein carbonyl levels were quantified as oxidative damage markers; superoxide dismutase and glutathione peroxidase activities, glutathione concentration, and the reduced glutathione/oxidized glutathione ratio were analyzed as antioxidant defense indicators. Mann-Whitney U tests were run. Statistical significance (a) was 0.05%. RESULTS: We included 29 rheumatoid arthritis patients, 10 with active disease, and 41 healthy controls. Age was higher in the rheumatoid arthritis group; there were no differences in female:male ratio between groups. Oxidative damage was higher in rheumatoid arthritis patients; however, there was no difference between patients with active or inactive rheumatoid arthritis. Antioxidant enzyme activities, glutathione concentration, and reduced glutathione/oxidized glutathione ratio were higher in rheumatoid arthritis patients than in controls. CONCLUSIONS: Antioxidant levels were higher in rheumatoid arthritis patients than in healthy controls; however, they were insufficient to prevent oxidative damage. This suggests an active oxidative process in rheumatoid arthritis patients.
27102921 Baseline CXCL10 and CXCL13 levels are predictive biomarkers for tumor necrosis factor inhi 2016 Apr 22 BACKGROUND: TNF inhibitors have been used as a treatment for moderate to severe RA patients. However, reliable biomarkers that predict therapeutic response to TNF inhibitors are lacking. In this study, we investigated whether chemokines may represent useful biomarkers to predict the response to TNF inhibitor therapy in RA. METHODS: RA patients (n = 29) who were initiating adalimumab or etanercept were recruited from the rheumatology clinics at Cooper University Hospital. RA patients were evaluated at baseline and 14 weeks after TNF inhibitor therapy, and serum levels of CXCL10, CXCL13, and CCL20 were measured by ELISA. Responders (n = 16) were defined as patients who had good or moderate response at week 14 by EULAR response criteria, and nonresponders (n = 13) were defined as having no response. RESULTS: Responders had higher levels of baseline CXCL10 and CXCL13 compared to nonresponders (p = 0.03 and 0.002 respectively). There was no difference in CCL20 levels. CXCL10 and CXCL13 were highly correlated with each other, and were higher in seropositive RA patients. CXCL10 and CXCL13 levels were decreased after TNF inhibitor therapy in responders. Baseline additive levels of CXCL10 + 13 were correlated with changes in DAS score at 14 weeks after TNF inhibitor therapy (r = 0.42, p = 0.03), and ROC curve analyses for predictive ability of CXCL10 + 13 showed an AUC of 0.83. CONCLUSIONS: Elevated baseline levels of CXCL10 and CXCL13 were associated with favorable response to TNF inhibitor therapy in RA. Subjects with high CXCL10 and high CXCL13 may represent a subset of RA patients whose inflammatory reactions are primarily driven by TNF.
27256711 CD8(+) T cells in human autoimmune arthritis: the unusual suspects. 2016 Jul CD8(+) T cells are key players in the body's defence against viral infections and cancer. To date, data on the role of CD8(+) T cells in autoimmune diseases have been scarce, especially when compared with the wealth of research on CD4(+) T cells. However, growing evidence suggests that CD8(+) T-cell homeostasis is impaired in human autoimmune diseases. The contribution of CD8(+) T cells to autoimmune arthritis is indicated by the close association of MHC class I polymorphisms with disease risk, as well as the correlation between CD8(+) T-cell phenotype and disease outcome. The heterogeneous phenotype, resistance to regulation and impaired regulatory function of CD8(+) T cells - especially at the target organ - might contribute to the persistence of autoimmune inflammation. Moreover, newly identified populations of tissue-resident CD8(+) T cells and their interaction with antigen-presenting cells might have a key role in disease pathology. In this Review, we assess the link between CD8(+) T cells, autoimmune arthritis and the basis of their homeostatic changes under inflammatory conditions. Improved insight into CD8(+) T cell-specific pathogenicity will be essential for a better understanding of autoimmune arthritis and the identification of new therapeutic targets.
26190565 Considerations on the appropriateness of the John Cunningham virus antibody assay use in p 2015 Oct OBJECTIVE: The John Cunningham virus (JCV) is a generally benign and asymptomatic polyomavirus. Due to an association of the anti-integrin agent natalizumab with progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS), a newly developed anti-JCV antibody assay has been implemented as a risk-stratification tool for natalizumab-treated patients with MS. This viewpoint offers insight and perspective regarding the potential unapproved use of the anti-JCV antibody assay in rheumatoid arthritis (RA) and examines how rheumatologists can best assist patients. METHODS: A primary literature search was conducted to identify articles on the number of cases of PML associated with natalizumab in patients with MS, the number of cases of PML associated with patients with rheumatic disease, PML incidence in the general population, serum-based assays to detect JCV exposure, and clinical PML presentation and treatment methods. RESULTS: Risk of PML in patients with RA receiving biologics appears orders of magnitude lower than that expected in natalizumab-treated patients with MS (1 in 1000). If patients with RA are risk stratified assuming an anti-JCV antibody seropositivity of 60%, theoretically 23,400 anti-JCV antibody-positive patients would have to receive rituximab before potentially observing 1 PML case. CONCLUSIONS: Data currently indicate that rheumatologists should not order the anti-JCV antibody assay for patients requiring biologics. Monitoring relevant symptoms indicative of emerging PML might provide greater value to patients, thus prompting interventional measures that could affect prognosis.
27943122 Shikonin inhibits TNF-α production through suppressing PKC-NF-κB-dependent decrease of I 2017 Apr Shikonin, a major effective component in the Chinese herbal medicine Lithospermum erythrorhizon Sieb., exhibits an anti-inflammatory property towards rheumatoid arthritis (RA), but the potential mechanism is unclear. Our aim was to investigate the mechanism of shikonin on the lipopolysaccharide (LPS)-induced fibroblast-like synoviocyte (LiFLS) inflammation model. Fibroblast-like synoviocytes (FLSs) were treated with 200 μg/ml of LPS for 24 h to establish the RA-like model, LiFLS. FLSs were pretreated with shikonin (0.1-1 μM) for 30 min in the treatment groups. Quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect mRNA and protein levels of interleukin (IL)-10 and tumor necrosis factor (TNF)-α. Signal proteins involved in IL-10 production were analyzed by Western blotting. Shikonin significantly reversed the inhibitory effects of LPS on IL-10 expression in FLSs by inactivating the PKC-NF-κB pathway. In addition, shikonin inhibited LPS-induced TNF-α expression in FLSs, and this effect was markedly diminished by IL-10-neutralizing antibody. The IL-10-mediated suppression of TNF-α transcription was demonstrated by no response to the protein synthesis inhibitor cyclohexamide and no mRNA decay. Shikonin inhibits LPS-induced TNF-α production in FLSs through suppressing the PKC-NF-κB-dependent decrease in IL-10, and this study also highlights the potential application of shikonin in the treatment of RA.
26771700 [MMPI-2 profiles in groups of systemic autoimmune disease - rheumatoid arthritis and syste 2015 OBJECTIVE: Systemic autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are characterized by the alteration of immunological response, which can damage many organs and systems and result in a wide variety of clinical presentations. In addition to physical symptoms, psychiatric disorders are also common to many autoimmune diseases. Anxiety, depression, psychosis and cognitive deficits have the highest prevalence. The aim of this study was to display the degree of psychopathological symptoms in patients with RA and SLE. METHODS: Female inpatients with RA (N=68) and SLE (N=78) were recruited from the Rheumatology and Immunology Clinic of the University of Pecs and were asked to complete the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and a short demografical form. The clinical personality profiles of the patient groups were explored and compared with each other. RESULTS: High scores (above 64T) were detected on the Hypochondriasis (Hs), Depression (D) and Hysteria (Hy) scales in both groups. Besides, the participants performed elevated scores on the Masculinity-Feminity (Mf), Psychasthenia (Pt) and Social Introversion (Si) clinical scales. They scored in the elevated range on the Physical Malfunctioning, Subjective Depression, Lassitude-Malaise and Somatic Complaints subscales of the neurotic triad. No significant difference was found on the ten clinical scales between the SLE and RA patients. CONCLUSION: Characteristics of MMPI-2 profiles in SLE and RA patients seem to be the consequence of the disease and a common feature of chronic conditions. High scores on the neurotic triad scales may reflect the comorbid psychiatric disorders and the somatic symptoms alike, so further investigations with the revised Hungarian MMPI-2 are needed.
26239594 Comparable effect of partly supervised and self-administered exercise programme in early r 2015 Aug INTRODUCTION: There is a need to establish a framework and exercise level for patients with early rheumatoid arthritis (RA). The aim of this study was to compare the effect of a partly supervised and a self-administered exercise programme for patients with early RA. METHODS: A total of 51 patients with early (≤ 5 years) RA were randomised to either a six-week supervised, progressive, high-intensity exercise programme followed by a six-week self-administered exercise programme or a 12-week self-administered exercise programme. RESULTS: A total of 36 patients completed the study. Following the 12 weeks of exercises, patients in the two groups had improved both their muscle strength and their physical fitness. There was a significant difference in Disease Activity Score in 28 joints calculated with C-reactive protein between the two exercise groups, but no significant differences in physical fitness, pain perception, Health Assessment Questionnaire, Short Form 36 health survey questionnaire, Fear-Avoidance Beliefs Questionnaire, or in muscle strength, except from a significant difference in trunk extensors. The dropout was 40% in the supervised group versus 20% in the self-administered group. CONCLUSION: A progressive, high-intensity exercise programme is feasible for patients with early RA, although we observed an elevated number of dropouts for reasons not related to the intervention. The partly supervised exercise programme with follow-up after 12 weeks does not seem to be more effective than the self-administered exercise programme. FUNDING: none. TRIAL REGISTRATION: The trial was registered with www.clinicaltrials.gov (NCT01553305).
25350077 The association of mannose-binding lectin genetic polymorphisms with the risk of rheumatoi 2015 OBJECTIVE: To better understand the risks of rheumatoid arthritis (RA) and certain subsets conferred by mannose-binding lectin (MBL2) polymorphisms in different races. MATERIALS AND METHODS: Eighteen articles (4810 cases and 4585 controls) were identified from the latest literature search carried out in May 2014 using PubMed, Web of Science, Wanfang Database (Chinese) and Chinese National Knowledge Infrastructure. Three single nucleotide polymorphisms of codon 52, 54 and 57, exonic and extended genotypic variance in MBL2 were synthesized. RESULTS: Codon 54 mutation of MBL2 was unlikely to be a risk factor for RA in overall population, but turned out to be deleterious in East Asian (four studies with 523 cases and 647 controls, pooled OR:1.63, 95% CI: 1.23-2.17). Codon 54 mutation increased the risk of seropositive and erosive RA by 44% and 162%, respectively (three studies with 281 cases and 358 controls, 95% CI: 1.01-2.05; 3 studies with 180 cases and 499 controls, 95% CI: 1.77-3.88). Furthermore, those risks were relatively stronger when restricted in East Asian (two studies with 147 cases and 244 controls, pooled OR: 1.85, 95% CI: 1.19-2.87; 2 studies with 170 cases and 291 controls, pooled OR: 2.78, 95% CI: 1.85-4.20). No remarkable associations were detected regarding codon 52, 57, exon 1 and extended genotype of MBL2. CONCLUSIONS: Polymorphism of codon 54 in MBL2 may predispose to RA, especially seropositive or erosive RA, which East Asian appears to be more vulnerable.
26810813 A model-based evaluation of single metrics for discriminating changes in rheumatoid arthri 2016 Jun AIMS: Composite indices for quantifying rheumatoid arthritis (RA) disease activity such as the 28-joint disease activity score (DAS28) are comprised of single parameters ('metrics') in various combinations. Population modelling methods were used to evaluate single metrics for their ability to reflect changes in disease activity with a view to understanding and improving composite indices. METHODS: A total of 11 single metrics of RA disease activity (tender and swollen joint counts, acute phase reactants and global health, pain and physical function assessments) were obtained from 203 patients with recent onset RA. Participants received combination disease-modifying anti-rheumatic drugs (DMARDs) according to a treat-to-target approach with a pre-defined protocol for treatment intensification. Models describing each metric's magnitude and variability of change from baseline to a single 'treated' state in the population were developed using nonmem(®) . Measures that displayed uniformly large changes between states across the population were ranked higher in terms of discriminatory capacity. RESULTS: Joint counts demonstrated a greater ability to discriminate changes in RA disease activity than others. Correlations between metrics demonstrated that erythrocyte sedimentation rate (ESR) had limited relationships with others for baseline scores and changes in RA disease activity (r generally < 0.2). However it appeared to be important in describing changes for those individuals where ESR levels were initially elevated. CONCLUSION: It appears unlikely that a single group of metrics may be suitable to capture disease activity changes across all RA patients and defining the most appropriate metric(s) for individual patients will be an important area of future research.
26295477 Brazilin Limits Inflammatory Responses through Induction of Prosurvival Autophagy in Rheum 2015 Brazilin is an active compound of Caesalpinia sappan L. (Leguminosae), which possesses pro-apoptotic and anti-inflammation potentials depending on the specific cell type. However, it is largely unknown whether autophagy is implicated in the mechanism underlying its chemotherapeutic and anti-inflammatory effects in rheumatoid arthritis (RA). Here, we show that treatment of RA fibroblast-like synoviocytes (FLS) with brazilin results in enhanced level of autophagic flux, evidenced by accumulation of autophagosome and increased level of lipidated LC3 (LC3-II), which is mainly mediated by enhanced production of reactive oxygen species (ROS). Interestingly, long-term exposure of brazilin was able to restore cell survival against the cytotoxity, exclusively in RA FLS, but not in normal fibroblast. Importantly, such a restoration from brazilin-induced cytotoxity in RA FLS was completely abrogated after co-treatment with autophagy inhibitors including NH4Cl or chloroquine. Furthermore, we found that the pretreatment of RA FLS with brazilin reduced LPS- or TNF-induced NF-κB activation and the secretion of inflammatory cytokines in parallel with the enhanced autophagic flux. Such anti-NF-κB potentials of brazilin were drastically masked in RA FLS when autophagy was suppressed. These results suggest that brazilin is capable of activating autophagy exclusively in RA FLS, and such inducible autophagy promotes cell survival and limits inflammatory response.
27580864 HLA DRB1/DQB1 alleles and DRB1-DQB1 haplotypes and the risk of rheumatoid arthritis in Tun 2016 Sep Rheumatoid arthritis (RA) is an inflammatory disease, which affects synovial joints, and is influenced by environmental and genetic factors, in particular the human leucocyte antigen (HLA) system. In our study, we investigated the association of HLA class II DRB1 and DQB1 alleles and DRB1-DQB1 haplotypes with RA susceptibility in Tunisian subjects. Therefore, HLA class II low-resolution genotyping was done in 110 RA patients and 116 controls, with a HLA-DRB1*04 high-resolution typing. Our results showed a strong association between HLA-DRB1*04/DRB1*04:05 alleles and RA presence, which persisted after correcting for multiple comparisons (Pc < 10-3, Pc = 0.020, respectively), in contrast to the protective effect of HLA-DRB1*04:03 allele (Pc = 15.2 × 10-4). However, increased frequency of DQB1*05 (Pc = 0.020) and decreased frequency of DRB1*04:03 subtype (Pc = 0.032) were seen in RF+ patients than controls. Moreover, when RA patients were compared to controls, DRB1*04-DQB1*03 haplotype was associated with RA susceptibility in Tunisians (Pc = 16.8 × 10-5), independently of RF status. Conversely, DRB1*01 allele and DRB1*01-DQB1*05 haplotype was highly present in RF+ vs RF- groups (Pc < 10-3, Pc = 5.6 × 10-3, respectively) and seems to be linked to seropositivity. Investigation of HLA class II alleles and haplotypes association with RA susceptibility with secondary Sjögren's syndrome (sSS) showed a predisposing effect of DRB1*04 (Pc < 10-3) and DRB1*04-DQB1*03 haplotype when RA with sSS/without sSS groups were compared to healthy controls. Our results confirms the association of HLA-DRB1*04, specifically HLA-DRB1*04:05 subtype, and DRB1*04-DQB1*03 haplotype with RA susceptibility in Tunisians, independently of seropositivity or the sSS presence.
28343615 Intra-articular injection with triamcinolone hexacetonide in patients with rheumatoid arth 2017 Mar OBJECTIVES: To evaluate local joint variables after intra-articular injection with triamcinolone hexacetonide in rheumatoid arthritis patients. METHODS: We blindly and prospectively (baseline, 1, 4, 12 and 24 weeks) evaluated metacarpophalangeal, wrist, elbow, shoulder, knee and ankle joints after triamcinolone hexacetonide intra-articular injection by the following outcome measures: visual analogue scale 0-10cm (VAS) for rest pain (VASR); VAS for movement pain (VASM); VAS for joint swelling (VASSw); flexion (FlexG) and extension (ExtG). RESULTS: 289 patients (635 joints) were studied. VASSw (p<0.001) and VASR (0.001
25962601 Macrophage activity assessed by soluble CD163 in early rheumatoid arthritis: association w 2015 Jul OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease where TNF-α is a central mediator of inflammation, and is cleaved from the cell surface by TACE/ADAM17. This metalloproteinase is also responsible for the release of soluble (s) CD163. Soluble CD163 reflects macrophage activation. In RA, sCD163 has been suggested as a marker of disease activity and progression. Our aim is to investigate sCD163 levels in early RA patients. METHODS: Soluble CD163 was measured by ELISA from 150 RA plasma samples from the OPERA trial. Averaged disease duration was three months, prior to randomisation with methotrexate (MTX) and adalimumab (DMARD+ADA) or MTX and placebo (DMARD+PLA). Soluble CD163 levels were evaluated in relation to clinical disease parameters. RESULTS: Plasma sCD163 at baseline was 2.39 mg/l (1.74 mg/l-3.18 mg/l), mean (95% CI), vs healthy controls: 1.63 mg/l (1.54 mg/l - 1.73 mg/l), (p<0.001). After three months of treatment sCD163 levels decreased significantly (average 23.5%) in both treatment groups. Significant incremental sCD163 levels followed withdrawal of ADA after 12 months of treatment. Baseline sCD163 correlated with CRP and all investigated disease activity markers (ρ=0.16-0.28, p<0.05). In the DMARD+PLA group baseline sCD163 also correlated with CRP during the follow-up period. CONCLUSIONS: Soluble CD163 correlated with disease activity markers in early RA before treatment. Plasma sCD163 may add to currently available disease measures by specifically reflecting changes in macrophage activity as evidenced by increasing levels following anti-TNF withdrawal, despite maintenance of a stable clinical condition achieved by conventional remedies. It remains to be determined whether sCD163 is an early predictor of disease flare.