Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
28437846 Association Between Pain Sensitization and Disease Activity in Patients With Rheumatoid Ar 2018 Feb OBJECTIVE: Pain sensitization may contribute to pain severity in rheumatoid arthritis (RA), impacting disease activity assessment. We examined whether pain processing mechanisms were associated with disease activity among RA patients with active disease. METHODS: The study included 139 subjects enrolled in the Central Pain in Rheumatoid Arthritis cohort. Subjects underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at multiple sites, conditioned pain modulation, and temporal summation. RA disease activity was assessed using the Clinical Disease Activity Index (CDAI) and its components. We examined cross-sectional associations between QST measures and disease activity using linear regression. RESULTS: Low PPTs (high pain sensitization) at all sites were associated with high CDAI scores (P ≤ 0.03) and tender joint counts (P ≤ 0.002). Associations between PPTs and patient global assessments were also seen at most sites. High temporal summation at the forearm (also reflecting high pain sensitization) was significantly associated with high CDAI scores (P = 0.02), patient global assessment scores (P = 0.0006), evaluator global assessment scores (P = 0.01), and tender joint counts (P = 0.02). Conversely, conditioned pain modulation (a measure of descending inhibitory pain pathways) was associated only with tender joint count (P = 0.03). CONCLUSION: High pain sensitization is associated with elevations in disease activity measures. Longitudinal studies are underway to elucidate the cause-effect relationships between pain sensitization and inflammatory disease activity in RA.
29855349 Association between inflammation and systolic blood pressure in RA compared to patients wi 2018 Jun 1 BACKGROUND: The relationship between inflammation and blood pressure (BP) has been studied mainly in the general population. In this study, we examined the association between inflammation and BP across a broader range of inflammation observed in rheumatoid arthritis (RA) and non-RA outpatients. METHODS: We studied subjects from a tertiary care outpatient population with C-reactive protein (CRP) and BP measured on the same date in 2009-2010; RA outpatients were identified using a validated algorithm. General population data were obtained from the National Health and Nutrition Examination Survey (NHANES) as comparison. To study the cross-sectional association between CRP and BP in the three groups, we constructed a generalized additive model. Longitudinal association between CRP and BP was examined using a repeated-measures linear mixed-effects model in RA outpatients with significant change in inflammation at two consecutive time points. RESULTS: We studied 24,325 subjects from the outpatient population, of whom 1811 had RA, and 5561 were from NHANES. In RA outpatients, we observed a positive relationship between CRP and systolic BP (SBP) at CRP < 6 mg/L and an inverse association at CRP ≥ 6 mg/L. A similar inverse U-shaped relationship was observed in non-RA outpatients. In NHANES, we observed a positive relationship between CRP and SBP as demonstrated by previous studies. Longitudinal analysis in RA showed that every 10 mg/L increase in CRP was associated with a 0.38 mmHg reduction in SBP. CONCLUSIONS: Across a broad range of CRP observed in RA and non-RA outpatients, we found an inverse U-shaped relationship between CRP and SBP, highlighting a relationship not previously observed when studying the general population.
29584787 Factors affecting walking ability in female patients with rheumatoid arthritis. 2018 OBJECTIVE: To determine the factors associated with gait parameters in female patients with rheumatoid arthritis (RA). METHODS: The gait analysis was performed in a large cohort of RA patients, and three basic gait parameters (step length, cadence and gait speed) were calculated. Clinical and laboratory data were also collected. Factors associated with gait parameters were analyzed using multivariable linear regression in the three models with forced entry. Then, we divided those patients with Health Assessment Questionnaire disability index (HAQ) scores ≤ 0.5 into two groups according to their gait speed that were compared to identify the characteristics of patients with a good HAQ score but poor walking ability. RESULTS: A total of 318 female patients were analyzed. Knee extension strength had the strongest positive association with all three gait parameters (P < 0.0001), while methotrexate use was also positively associated with all three gait parameters (step length: P < 0.05, cadence: P < 0.05 in model 1 and 2; P < 0.01 in model 3, gait speed: P < 0.01). The disease activity score was negatively associated with step length and gait speed (step length, gait speed: P < 0.01 in model 1 and 2; P < 0.05 in model 3). 26% of patients with good HAQ scores showed slow gait speed. Patients with good HAQ scores and slow gait speed had higher disease activity scores (P < 0.05) and lower knee extension strength (P < 0.0001) than those with good HAQ scores and normal gait speed. CONCLUSIONS: High knee extension strength, low disease activity and administration of methotrexate were strongly associated with good walking ability in female patients with RA. And, even if patients showed good HAQ scores, about quarter of those patients had poor walking ability, and they showed higher disease activity, lower knee extension strength, compared to the patients with normal gait speed.
29278339 Determinants of Patient's Global Assessment of Disease Activity and Physician's Global Ass 2018 Nov OBJECTIVES: To assess the determinants of Patient's Global Assessment of Disease Activity (PtGA) and Physician's Global Assessment of Disease Activity (PhGA) in overall and Japanese patients with rheumatoid arthritis (RA) from two large randomized controlled trials. METHODS: Post hoc analysis of overall and Japanese RA patients who had previous inadequate responses to methotrexate or who had no/minimal previous disease-modifying antirheumatic drug treatment. We examined correlations between PtGA/PhGA and tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), inflammatory markers, pain visual analog scale (VAS), and other patient-reported outcomes at baseline, Week 12, and Week 24. Determinants of PtGA/PhGA were identified. RESULTS: In overall populations, pain VAS was the main determinant of PtGA, whereas TJC28 was the main determinant of PhGA in both studies. In Japanese populations, consistent with overall populations, pain VAS was the main determinant of PtGA in both studies; in contrast to overall populations, pain VAS and SJC28/TJC28 played an important role in PhGA. CONCLUSION: Pain was the most important determinant of PtGA, whereas determinants of PhGA varied between populations/studies and were mostly explained by pain/joint counts. Physicians should be aware of patients' perceptions of disease activity when performing assessments/prescribing treatments.
30138480 Serum matrix metalloproteinase 3 levels are associated with an effect of iguratimod as add 2018 OBJECTIVE: The aim of this study was to clarify whether serum matrix metalloproteinase 3 (MMP-3) levels are associated with an effect of iguratimod as add-on therapy to biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA). METHODS: Forty three patients with RA were treated with iguratimod as add-on therapy to bDMARDs. They were classified into remission and non-remission groups at 24 weeks of iguratimod therapy. Remission was defined as a state with a disease activity score (DAS) <2.6 in 28 joints (termed DAS remission) and total power Doppler ultrasound (US) score <3 (termed US remission). The serum MMP-3 levels at baseline and at 12 weeks were compared between these two groups. RESULTS: There were no significant differences in the serum MMP-3 levels at baseline between the DAS and US remission groups and the non-remission group. The serum MMP-3 levels at 12 weeks in the US remission group were significantly lower than those in the non-remission group. The ratios of the serum MMP-3 levels at baseline to those at 12 weeks in both the DAS and US remission groups were significantly lower than those in the non-remission group. An MMP-3 ratio <0.86 was determined as the cut-off value to predict US remission at 24 weeks. CONCLUSION: Our findings suggest that the ratios of the serum MMP-3 levels at baseline to those at 12 weeks could be used to predict remission in RA patients who are administered iguratimod as an add-on to bDMARDs.
28758586 Effects of the Disease Characteristics and the Treatment on Psychological Status in Patien 2018 INTRODUCTION: Various psychiatric disorders, especially depression and anxiety, are seen in 2/3 of the chronic rheumatic diseases with chronic pain. In this study, we aimed to define anxiety and depression rates in Rheumatoid Arthritis (RA) and Ankylosing Spondylitis (AS) patients (under treatment) with similar age and gender; to compare the obtained data with each other and healthy control group; and also we aimed to investigate the relationship between human leukocyte antigen B27(HLA-B27) in AS, Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) in RA with anxiety and depression. METHOD: 46 patients with RA, 43 patients with AS and 29 healthy volunteers were evaluated with Beck Depression Inventory (BAI) and Beck Anxiety Inventory (BAI). Participants were also noted for their educational status, occupation status, family history of illness, duration of the disease and their current treatments. Then we compared the obtained data with the healthy control group. SPSS (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.p=0. Armonk, NY: IBM Corp.) was used for performing statistical analysis. RESULTS: There was no difference between the groups according to age, sex, duration of illness (p=0.104, p=0.767, p=0.377). A significant difference between groups in terms of BAI values were determined (p=0.018). In subgroup analyzes, the median BAI value of AS group was found to be higher than the control group (p=0.020). There were no differences in BAI values between AS and RA groups or between RA and the control groups (p>0.05, p>0.05 respectively). Also, there were no differences between the groups in terms of BDI values (p=0.055). CONCLUSIONS: Especially, chronic pain-related diseases are often associated with mental disorders, especially depression and anxiety. As a result, a multidisciplinary approach including psychiatric support should be used when planning treatment for these patients.
30785689 [Novel hepatokine in rheumatoid arthritis laboratory diagnostics.]. 2018 Fetuin-A (α2-Heremans-Schmid glycoprotein, AHSG) is a glycoprotein mainly secreted by hepar in adults. It was shown, that AHSG is a positive as well as a negative acute-phase protein with pro- and anti-inflammatory effects. We studied serum levels of an AHSG in patients with rheumatoid arthritis (RA) and healthy controls in order to determine its role in the diagnostics of this disease. We measured serum levels of AHSG in 110 patients with RA and 30 healthy controls. To determine RA phenotype we measured rheumatoid factor and anticitrullinated protein antibodies. All patients were examined by the rheumatologist to identify clinical features of RA. Serum CRP and ESR were measured to assess inflammation. Mean level of AHSG in group with RA was 765,67±120,66 (Hereinafter M±σ), which was significantly lower than of healthy controls (812,76,2±76,2 μg/ml; p=0,0437). Insignificant difference of mean levels of AHSG was observed between men and women with RA (p=0,424). The reference ranges for AHSG measured from the healty controls were 653,55-972,19 ug/ml (M±2σ). We studied mean levels of AHSG according to the clinical and immunological manifestations of RA. AHSG levels were significantly lower within patients positive on ACCP, with moderate or high disease activity, with 2nd, 3rd and 4th x-ray stages and functional classes, with erosivity, extra-articular manifestations and complications. The moderate negative correlation was observed between AHSG level and CRP (r=-0,3146; p<0,001), ESR (r=-0,344; p<0,001) and DAS28 (r=-0,4334; p<0,001). In summary, AHSG mean levels were significantly different in patients with RA. It can be used to improve the diagnostics of RA activity, severity, extra-articular manifestations and complications.
29370811 Harm, benefit and costs associated with low-dose glucocorticoids added to the treatment st 2018 Jan 25 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints affecting 1% of the world population. It has major impact on patients through disability and associated comorbidities. Current treatment strategies have considerably improved the prognosis, but recent innovations (especially biologic drugs and the new class of so-called "JAK/STAT inhibitors") have important safety issues and are very costly. Glucocorticoids (GCs) are highly effective in RA, and could reduce the need for expensive treatment with biologic agents. However, despite more than 65 years of clinical experience, there is a lack of studies large enough to adequately document the benefit/harm balance. The result is inappropriate treatment strategies, i.e. both under-use and over-use of GCs, and consequently suboptimal treatment of RA. METHODS: The GLORIA study is a pragmatic multicentre, 2-year, randomised, double-blind, clinical trial to assess the safety and effectiveness of a daily dose of 5 mg prednisolone or matching placebo added to standard of care in elderly patients with RA. Eligible participants are diagnosed with RA, have inadequate disease control (disease activity score, DAS28 ≥ 2.6), and are ≥ 65 years. The primary outcome measures are the time-averaged mean value of the DAS28 and the occurrence of serious adverse events or adverse events of special interest. During the trial, change in antirheumatic therapy is permitted as clinically indicated, except for GCs. Cost-effectiveness and cost-utility are secondary outcomes. The main challenge is the interpretation of the trial result with two primary endpoints and the pragmatic trial design that allows co-interventions. Another challenge is the definition of safety and the relative lack of power to detect differences between treatment groups. We have chosen to define safety as the number of patients experiencing at least one serious adverse event. We also specify a decision tree to guide our conclusion on the balance of benefit and harm, and our methodology to combat potential confounding caused by co-interventions. DISCUSSION: Pragmatic trials minimise impact on daily practice and maximise clinical relevance of the results, but analysis and interpretation of the results is challenging. We expect that the results of this trial are of importance for all rheumatologists who treat elderly patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02585258 . Registered on 20 October 2015.
30075427 Analysis of miRNA expression in patients with rheumatoid arthritis during remission and re 2018 Oct The physiopathology of rheumatoid arthritis (RA) is mediated by proinflammatory cytokines, some of which are regulated by the JAK/STAT pathway. Tofacitinib is a JAK inhibitor, but its role in the regulation of microRNAs (miRNAs) is unknown. There is also no information regarding the role of miRNAs in the clinical relapse/remission of RA. The present project aims to identify a signature profile of miRNA expression in a subgroup of RA patients who had to discontinue tofacitinib treatment (because of the ending of a 5-year open-label clinical trial) and to describe the expression of miRNAs during RA remission or flare-up. The relative expression of 61 miRNAs was determined in serum samples with the Firefly™ BioWorks assay. Statistical analysis was performed by means of Student's t-test and heatmap analysis was performed with Firefly™ Analysis Workbench software and in the software GraphPad® Prism v5.0. Target prediction and Gene Ontology analysis were carried out using bioinformatic tools. We found a distinctive signature of miRNA expression associated with relapse, featuring upregulated expression of hsa‑miR‑432‑5p (p < 0.05). We also found upregulation of hsa‑miR‑194‑5p (p < 0.05) in samples of patients with RA flare-up. Gene Ontology analysis of the target genes for hsa‑miR‑432‑5p was performed to identify relevant pathways associated with relapse; the implications of these pathways in the physiopathology of RA are discussed. Tofacitinib treatment does not have a direct effect on the expression of measured miRNAs. The changes in hsa‑miR‑432‑5p and hsa‑miR‑194‑5p are associated with the regulation of proinflammatory pathways and RA flare-up.
29460148 Impact of vitamin D deficiency on clinical parameters in treatment-naïve rheumatoid arth 2018 Nov OBJECTIVE: To determine if patients with rheumatoid arthritis (RA) are at risk of vitamin D deficiency and whether the levels of vitamin D are correlated with clinical parameters in RA. METHODS: A total of 280 treatment-naïve RA patients, and 140 age- and sex-matched healthy volunteers were enrolled. Serum levels of 1,25-dihydroxycholecalciferol (1,25(OH)(2)D(3)), the active form of vitamin D, were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of 1,25(OH)(2)D(3) less than 25 ng/mL were defined as insufficient. Linear regression was performed to evaluate correlations as (modifying and) confounding factors were controlled. RESULTS: The levels of serum 1,25(OH)(2)D(3) in RA individuals (12.24 ± 6.68 ng/ml) were significantly lower than in healthy controls (21.08 ± 7.14 ng/ml; p < 0.05). An inverse association was found between the levels of 1,25(OH)(2)D(3) and ESR in obese and overweight individuals with RA (β(obese) = -0.385, β(overweight) = -0.395, both p < 0.05), but not in normal and underweight subjects. A significant negative association between levels of 1,25(OH)(2)D(3) and DAS28 score (β = -0.164, p = 0.018) was observed. The levels of 1,25(OH)(2)D(3) were associated moderately and inversely with the absolute numbers of Th-17 (β = -0.158, p = 0.019) and positively with those of CD4(+) regulatory T (Treg) cell (β = 0.146, p = 0.025). The levels of 1,25(OH)(2)D(3) in anti-cyclic citrullinated peptide (anti-CCP)-positive patients with RA were lower than in the anti-CCP-negative RA patients (10.86 ng/ml versus 15.98 ng/ml; t = -3.08, p < 0.01). CONCLUSIONS: A significant association was observed between levels of vitamin D and parameters of disease, including body mass index (BMI), DAS28, Th17 cell counts, Treg cell counts, and presence of anti-CCP antibody in RA patients.
28363826 Precision and sources of variability in the assessment of rheumatoid arthritis erosions by 2018 Mar OBJECTIVES: To assess the precision and the sources of variation due to repositioning of the manual measurement of erosions located on the metacarpophalangeal joints (MCP) with High-Resolution peripheral Quantitative Computed Tomography (HRpQCT) in rheumatoid arthritis (RA). METHODS: RA patients with at least one erosion on the 2nd, 3rd or 4th MCP on conventional radiographs were included. Two scans were performed the same day with repositioning. The main outcome was to calculate the short-term precision of the width, depth, and volume of erosions. Secondary outcomes were intra-operator and inter-operator precision, the least significant change, and the sources of variability of the measurement. RESULTS: Twenty-nine patients were included, allowing analysis of 406 erosions from 0.9 to 3mm of diameter. Intraclass correlation coefficients (ICC) for the precision of the measurement of the axial width, axial depth, and volume after repositioning were 0.80, 0.96, and 0.99, respectively. RMS CV and RMS SD were 16%, 0.26mm; 17.5%, 0.32mm; and 19.7%, 0.93mm(3), respectively. For intra-operator precision, ICCs were 0.92, 0.97, and 0.99 with RMS CV of 16%, 16.4%, and 18.7%, respectively. Inter-operator precision of the volume was 0.99 with RMS CV of 14%. Least significant change of width, depth, and volume were 0.3mm, 0.2mm, and 0.3mm(3). There was no significant correlation with bone microarchitecture parameters. CONCLUSION: HRpQCT analysis is a reproducible method to characterize and measure erosions, without effect of the repositioning. However, we showed weak precision in manual measurement due to intra-operator variability.
29520081 Evaluation of a clinical pharmacogenetics model to predict methotrexate response in patien 2018 Jul Variability of response to treatment hinders successful management of rheumatoid arthritis (RA). Consequently, a clinical pharmacogenetics model for predicting response to methotrexate (CP-MTX) has been previously proposed that includes four clinical variables (disease activity, sex, the presence of rheumatoid factor and smoking status) and four SNPs (rs2236225, rs17602729, rs1127354, and rs2372536) in genes of the folate pathway. It showed good performance, but failed to attract attention, likely, in relation with lack of clear clinical benefit. Here, we have revised the value of the CP-MTX model directly addressing its clinical benefit by focusing on the expected benefit-cost of the predictions. In addition, our study included a much larger number of RA patients (n = 720) in MTX monotherapy than previous studies. Benefit of CP-MTX prediction was defined as the patients that would have received combination therapy as first treatment because they were correctly predicted as non-responders to MTX monotherapy. In contrast, cost of CP-MTX prediction was defined as the responder patients that were wrongly predicted as non-responders. Application of CP-MTX predictions to our patients showed a good benefit-cost relationship, with half of the 66.7% non-responders to MTX monotherapy rightly directed to alternative treatments (a benefit of 33.3%) at the cost of 8.5% wrongly predicted non-responders. These benefits-costs were consistent with reanalysis of the previously published studies. Therefore, predictions of CP-MTX showed a good benefit-cost relationship for informing MTX prescription.
29080437 Nursing sensitive outcomes in patients with rheumatoid arthritis: A systematic literature 2018 Jan BACKGROUND: Although rheumatology nursing has been shown to be effective in managing patients with rheumatoid arthritis, patient outcomes sensitive to nursing interventions (nursing sensitive outcomes) have not been systematically studied. OBJECTIVES: The objective of this study was to identify and delineate relevant patient outcomes measured in studies that reported nursing interventions in patients with rheumatoid arthritis. DESIGN: A systematic search was conducted from 1990 to 2016. Inclusion criteria were (i) patients with rheumatoid arthritis, (ii) adult population age ≥16years, (iii) nurse as part of the care team or intervention delivery, (iv) primary research only, (v) English language, and (vi) quantitative studies with nursing sensitive outcomes. DATA SOURCES: Medline, CINAHL, Ovid nursing, Cochrane library and PsycINFO databases were searched for relevant studies. REVIEW METHODS: Using the predetermined inclusion/exclusion criteria, nine reviewers working in pairs assessed the eligibility of the identified studies based on titles and abstracts. Papers meeting the inclusion criteria were retrieved and full texts were further assessed. Critical Appraisal Skills Programme tools were used to assess the quality of the included studies. Data on nursing sensitive outcomes were extracted independently by two reviewers. The Outcome Measures in Rheumatology comprehensive conceptual framework for health was used to contextualise and present findings. RESULTS: Of the 820 articles retrieved, 7 randomised controlled trials and 3 observational studies met the inclusion criteria. Seventeen nursing sensitive outcomes were identified (disease activity, clinical effects, pain, early morning stiffness duration, fatigue, patient safety issues, function, knowledge, patient satisfaction, confidence in care received, mental health status, self-efficacy, patient attitude/perception of ability to control arthritis, quality of life, health utility, health care resources, death). These fitted into 10 health intervention domains in keeping with the pre-specified conceptual framework for health: disease status, effectiveness, safety, function, knowledge, satisfaction, psychological status, quality of life, cost, death. A total of 59 measurement instruments were identified comprising patient reported outcome measures (n=31), and biologic measures and reports (n=28). CONCLUSIONS: This review is notable in that it is the first to have identified, and reported, a set of multidimensional outcome measures that are sensitive to nursing interventions in rheumatology specifically. Further research is required to determine a core set of outcomes to be used in all rheumatology nursing intervention studies.
30059653 Plasma lipidomic profile signature of rheumatoid arthritis versus Lyme arthritis patients. 2018 Sep 15 OBJECTIVES: Distinguishing of rheumatoid arthritis (RA) and Lyme arthritis (LA) is difficult, because of similar symptoms. This presents a significant clinical problem since treatments are quite different in both diseases. We investigated the plasma phospholipid profiles of RA and LA patients versus healthy subjects to find metabolic changes responsible for differentiation of both diseases. METHODS: Plasma was collected from 9 RA, 9 LA, and 9 healthy subjects. Extracted lipids were analyzed using LC- MS/MS to characterize phospholipid profiles of RA, LA and healthy subjects. Principal components analysis (PCA), partial least squares-discriminate analysis (PLS-DA) and variable importance in projection (VIP) scores were used to estimate the importance of each phospholipid variable. RESULTS: We identified 114 phospholipids in plasma. Phospholipid profiles were significantly different in RA and LA patients than in healthy subjects. Principal discriminant phospholipids between RA and LA groups were LPE (14:0), LPC(14:0) PI(18:0/20:4), PI(18:2/18:0), PI(16:1/18:2), PI(18:1/18:0), and PI(18:0/20:3). CONCLUSIONS: Our study provides insights into the alteration of the plasma phospholipid profile of LA patients, resulting from Borrelia burgdorferi infection, that may lead to improved LA diagnosis and differentiation of this disease from RA. Furthermore, LPE (14:0) was found to have a high potential to be a possible biomarker of LA.
29243056 Association between urinary sodium and potassium excretion and blood pressure and inflamma 2018 Apr Hypertension is highly prevalent in patients with rheumatoid arthritis (RA). In other populations, high sodium (Na(+)) and low potassium (K(+)) intake are associated with an increased risk of hypertension, and in animal models, a high salt intake exacerbated arthritis. Patients with RA have many comorbidities associated with salt sensitivity, but their salt intake and its relationship to blood pressure and inflammation is unknown. Using the Kawasaki formula, Na(+) and K(+) urinary excretion (reflecting intake) was estimated in 166 patients with RA and 92 controls, frequency matched for age, sex, and race. Inflammatory markers and disease activity were measured in RA patients. We tested the associations between blood pressure and Na(+) and K(+) excretion. Estimated 24-h Na(+) excretion was similarly high in both RA (median [IQR] 5.1 g, [3.9-6.6 g]) and controls (4.9 g, [4.0-6.5 g]), p = 0.9, despite higher rates of hypertension in RA (54 vs. 39%, p = 0.03). The Na(+):K(+) excretion ratio was significantly higher in RA (2.0 [1.6-2.4]) vs. 1.7 [1.5-2.1]), p = 0.02] compared to controls. In RA, a lower K(+) excretion was inversely correlated with diastolic blood pressure (adjusted β = - 1.79, p = 0.04). There was no significant association between Na(+) or K(+) excretion and inflammatory markers. Despite a similar Na(+) excretion, patients with RA had higher rates of hypertension than controls, a finding compatible with increased salt sensitivity. Patients with RA had a lower Na(+):K(+) excretion ratio than controls, and lower K(+) excretion was associated with higher diastolic blood pressure in RA.
29482627 Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment 2018 Feb 26 BACKGROUND: The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. METHODS: In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on (1) change in disease activity score (DAS)44 between 0 and 4 months, (2) initial drug-free remission (DFR, drug-free DAS44 < 1.6) achieved between 1 and 2 years of follow up, and (3) long-term sustained DFR until last follow up. RESULTS: Patients with a broad autoantibody profile at baseline had a significantly better early treatment response: ΔDAS 0-4 months of 1-2, 3-4, and 5-6 vs 7-8 isotypes, -1.5 (p < 0.001), -1.7 (p = 0.03), and -1.8 (p = 0.04) vs -2.2. Similar results were observed for AMPA number. However, patients with a broad baseline autoantibody profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar trends were observed. CONCLUSIONS: A broad baseline autoantibody profile is associated with a better early treatment response. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity, which could make the underlying disease processes initially more suppressible by medication. The lack of association with long-term sustained DFR suggests that the relevance of the baseline autoantibody profile diminishes over time. TRIAL REGISTRATION: ISRCTN11916566 . Registered on 7 November 2006. EudraCT, 2006- 06186-16. Registered on 16 July 2007.
29653213 Neutrophilic dermatoses: Pyoderma gangrenosum and other bowel- and arthritis-associated ne 2018 Dec Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders that present with unique clinical features but are unified by the presence of a sterile, predominantly neutrophilic infiltrate on histopathology. The morphology of cutaneous lesions associated with these disorders is heterogeneous, which renders diagnosis challenging. Moreover, a thorough evaluation is required to exclude diseases that mimic these disorders and to diagnose potential associated infectious, inflammatory, and neoplastic processes. While some neutrophilic dermatoses may resolve spontaneously, most require treatment to achieve remission. Delays in diagnosis and treatment can lead to significant patient morbidity and even mortality. Therapeutic modalities range from systemic corticosteroids to novel biologic agents, and the treatment literature is rapidly expanding. The second article in this continuing medical education series reviews the epidemiology, clinical characteristics, histopathologic features, diagnosis, and management of pyoderma gangrenosum as well as bowel-associated dermatosis-arthritis syndrome and the arthritis-associated neutrophilic dermatoses rheumatoid neutrophilic dermatitis and adult Still disease.
30106887 High Interleukin-37 (IL-37) Expression and Increased Mucin-Domain Containing-3 (TIM-3) on 2018 Aug 14 BACKGROUND Anti-inflammatory mediators such as mucin-domain containing-3 (TIM-3) and IL-37 play an important role in the regulation of Th1-mediated immunity. This study was designed to investigate the proportions of various T cell subsets and monocytes in the peripheral blood of rheumatoid arthritis (RA) patients, as well as the level of TIM-3 on these cells and serum cytokine levels. MATERIAL AND METHODS We enrolled 59 RA patients and 46 age- and sex-matched healthy controls in this study. The proportion of T cells and TIM-3 expression on these T cells were determined by flow cytometry. Cytokine levels in serum were determined by ELISA. RESULTS Compared with the healthy controls, the proportions of CD3+CD4+ T cells and CD3+CD4+CD25+CD127low T cells in the peripheral blood were significantly higher in RA patients. However, RA patients had significantly lower proportions of CD3+CD8+ T cells and CD3+CD4-CD8- T cells. TIM-3 was highly expressed on CD3+CD4+, CD3+CD8+, CD3+CD4+CD25+CD127low, and CD3+CD4-CD8- T cells, as well as CD14+ monocytes, in RA patients. Nevertheless, no correlation between TIM-3 level and an RA disease activity score of 28 was found. The elevated serum levels of IL-6 and IL-37 were positively correlated with tumor necrosis factor-α (TNF-α). CONCLUSIONS Both pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory mediators (TIM-3 and IL-37) simultaneously contribute to the pathogenesis of RA. TIM-3 and IL-37 may be used as potential biomarkers of active RA.
29843785 Oxidative stress impairs energy metabolism in primary cells and synovial tissue of patient 2018 May 29 BACKGROUND: In this study, we examined the effect of oxidative stress on cellular energy metabolism and pro-angiogenic/pro-inflammatory mechanisms of primary rheumatoid arthritis synovial fibroblast cells (RASFC) and human umbilical vein endothelial cells (HUVEC). METHODS: Primary RASFC and HUVEC were cultured with the oxidative stress inducer 4-hydroxy-2-nonenal (4-HNE), and extracellular acidification rate, oxygen consumption rate, mitochondrial function and pro-angiogenic/pro-inflammatory mechanisms were assessed using the Seahorse analyser, complex I-V activity assays, random mutation mitochondrial capture assays, enzyme-linked immunosorbent assays and functional assays, including angiogenic tube formation, migration and invasion. Expression of angiogenic growth factors in synovial tissue (ST) was assessed by IHC in patients with rheumatoid arthritis (RA) undergoing arthroscopy before and after administration of tumour necrosis factor inhibitors (TNFi). RESULTS: In RASFC and HUVEC, 4-HNE-induced oxidative stress reprogrammed energy metabolism by inhibiting mitochondrial basal, maximal and adenosine triphosphate-linked respiration and reserve capacity, coupled with the reduced enzymatic activity of oxidative phosphorylation complexes III and IV. In contrast, 4-HNE elevated basal glycolysis, glycolytic capacity and glycolytic reserve, paralleled by an increase in mitochondrial DNA mutations and reactive oxygen species. 4-HNE activated pro-angiogenic responses of RASFC, which subsequently altered HUVEC invasion and migration, angiogenic tube formation and the release of pro-angiogenic mediators. In vivo markers of angiogenesis (vascular endothelial growth factor, angiopoietin 2 [Ang2], tyrosine kinase receptor [Tie2]) were significantly associated with oxidative damage and oxygen metabolism in the inflamed synovium. Significant reduction in ST vascularity and Ang2/Tie2 expression was demonstrated in patients with RA before and after administration of TNFi. CONCLUSIONS: Oxidative stress promotes metabolism in favour of glycolysis, an effect that may contribute to acceleration of inflammatory mechanisms and subsequent dysfunctional angiogenesis in RA.
30167586 Does patients' opinion of remission in rheumatoid arthritis overlap ultrasound "true" remi 2018 Aug 30 AIM: Patients describe rheumatoid arthritis (RA) remission as the absence of any symptoms or return to normality. Residual ultrasound (US) synovitis was frequently described in remission cohorts in previous studies. US tenosynovitis evaluation and scoring seems to better follow clinical remission scores compared with synovitis in RA. Our objective was to verify the presence of US findings suggestive of persistent inflammation in a cohort of patients in remission according to their own opinion. MATERIALS AND METHODS: Forty-three RA patients were prospectively enrolled in this pilot study between 2015-2017 according to their positive answer to the question "Are you feeling free of symptoms, just like before your RA symptomsstarted?". Clinical evaluation of tender and swollen joints was performed in the same day with US evaluation of 24 joints and 26 tendon sites and lab C-reactive protein (CRP) evaluation. DAS28-CRP and SDAI were calculated. RESULTS: A total of 72.9% (35 of 43) of patients were in remission per DAS28 criteria. Except for CRP value, no other variables were significantly different in the 35 of 43. PD scoring in tenosynovitis of the ankle and feet was 100% overlapping remission felt by patients. PD tenosynovitis in both upper and lower limbs was found in less than 10% of patients, and only grade 1 (minimal). CONCLUSION:  A combination of patients' opinion and PDUS evaluation could be a starting point for RA treatment tapering.