Rheumatoid Arthritis Disease Activity Research Articles

Long Non-coding RNA Genes Polymorphisms H19 (rs2251375) and MALAT1 (rs3200401) Association with Rheumatoid Arthritis and Their Correlation with Disease Activity in a Cohort of Egyptian Patients: A Pilot Study.

Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory, autoimmune disease that could be disabling throughout its course. It affects people in their most reproductive years with relatively high morbidity and mortality. Long non-coding RNAs became one of the epigenetic mechanisms to prove a link to RA pathogenesis and development, including H19 and MALAT1 genes. These two genes' expressions had proved to increase in multiple diseases, attracting attention to their polymorphisms and their possible risk role. Assess the association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA and its disease activity. In this pilot study, 200 hundred subjects (100 RA patients and 100 healthy controls) were investigated for a possible link between the polymorphisms H19 SNP (rs2251375) and MALAT1 SNP (3200401) and RA susceptibility and disease activity. RA-related investigations and clinical assessment were done. Real-time PCR genotyping of both SNPs was done using TaqMan® MGB probes. There was no association between the SNPs and risk of developing RA. However, both SNPs had a significant association with high disease activity. H19 SNP (rs2251375) heterozygous genotype CA had an association with elevated levels of ESR (p = 0.04) and higher DAS28-ESR score (p = 0.03). MALAT1 (rs3200401) C allele had an association with elevated ESR (p = 0.001), DAS28-ESR (p = 0.03), and DAS28-CRP (p = 0.007), while CC genotype had an association with DAS28-CRP (p = 0.015). Linkage disequilibrium and haplotyping of the alleles of both SNPs were analyzed as both genes are present on chromosome 11, but no significant association was found between any of the combinations of the alleles (p > 0.05), denoting that (rs2251375) and (rs3200401) are not in linkage disequilibrium. There is no association between H19 SNP (rs2251375) and MALAT1 SNP (rs3200401) and the susceptibility of RA. However, there is an association between H19 SNP (rs2251375) genotype CA and MALAT1 SNP (rs3200401) genotype CC with RA high disease activity.

Evaluation of Omega-3 Effect as Adjuvant Therapy to Methotrexate on Alkaline Phosphatase Level in Iraqi Patients with Active Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a common inflammatory disease associated with many extraarticularfeatures. The aim: of the current study is to assess the influence of omega-3 fatty acids(EPA, DHA) on serum alkaline phosphatase in patients with active RA. A single blinded placebocontrolled clinical trial with 12 weeks follow up period at which 50 patients with active RAusing methotrexate were randomized into 2 groups to receive either omega-3 (1000 mg) capsulethree times daily or capsules prefilled with glucose as placebo and were evaluated at zero time(baseline) and after 12 weeks for alkaline phosphatase level in serum. In addition to twenty fivehealthy subjects as control group. The age of RA patients in omega-3 group ranged from 25-80years (50.36±2.46), whereas the age of RA patients in placebo group ranged from 35-68 years(50.08±1.84 ), while the age of apparently healthy subjects in control group where ranged from40-60 years (94.20±1.12). The RA disease activity was measured using disease activity score of28 joints(DAS28-ESR) and clinical disease activity index (CDAI). After 12 weeks of startingadjuvant treatment with either omega-3 or placebo, the results showed that there were nosignificant difference between the effect of omega- 3 and placebo on alkaline phosphatase level.In Conclusion, omega-3 significantly decreased alkaline phosphatase level in patient with activerheumatoid arthritis

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie.

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients often experience secondary non-response to a first-line tumour necrosis factor alpha inhibitor (TNFαi). This pooled analysis of six observational studies in Europe (GO-BEYOND program) provides an estimate of second-line golimumab (GLM) effectiveness for these rheumatic diseases. The GO-BEYOND studies included common disease-specific endpoints allowing for a pooled analysis. Patients had discontinued one prior TNFαi (due to loss of efficacy, tolerability, or inconvenience) and were followed for 12 months after GLM initiation. Primary endpoints included the proportion of patients achieving low disease activity (LDA, DAS28-CRP<3.2) in RA, minimal disease activity (MDA, fulfilment of 5 of 7 outcome measures) in PsA, or low disease activity (ASDAS<2.1) in axSpA at 6 months. Disease activity at 3 and 12 months and quality of life (QoL; EQ-5D-3L) were also assessed. Adverse events were monitored. Protocol-specified analyses were based on observed data. In 712 patients, (n=325, RA; 186, PsA; 201, axSpA), mean age was 54 years, 64% were female, and median disease duration was 5 years. Primary endpoints were achieved in 58.3% (RA), 45.5% (PsA), and 45.4% (axSpA) of patients; disease activity improvements were observed at 3 and 12 months and EQ-5D-3L results showed improved QoL over time. The treatment persistence rate at 12 months was 67.8% of patients. No new safety signals were observed. This pooled analysis of the GO-BEYOND studies showed that treatment with GLM was effective and represented a valid second-line option for RA, PsA, and axSpA patients.

Risk Factors and Clinical Outcomes Associated With Sarcopenia in Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

Sarcopenia is underrecognized in patients with rheumatoid arthritis (RA). Risk factors of sarcopenia and its impact on outcomes in RA patients are relatively unknown. We conducted a systematic review to identify factors and outcomes associated with sarcopenia in RA. We conducted this review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. We searched PubMed, Embase, CINAHL, and Web of Science databases by combining the following search concepts: (1) RA and (2) sarcopenia. Articles were included if they included RA patients, assessed for sarcopenia using a consensus working group definition, and assessed for clinical outcomes. Meta-analysis was performed using studies that shared the same sarcopenia definition and consistency in reporting patient or disease variables. Our search identified 3602 articles. After removal of duplicates, title and abstract screen, and full-text review, 16 articles were included for final analysis. All studies had observational study designs. The pooled prevalence of sarcopenia ranged from 24% to 30%, depending on the criteria for sarcopenia used. Factors associated with sarcopenia included higher 28-joint Disease Activity Scale scores (+0.39; 95% confidence interval, +0.02 to +0.77) and baseline methotrexate use (odds ratio, 0.70; 95% confidence interval, 0.51-0.97). Baseline glucocorticoid use had a positive correlation with sarcopenia in multiple studies. Several studies found lower bone mineral density and higher incidence of falls and fractures in patients with sarcopenia. Sarcopenia is prevalent in RA, and it may be associated with higher RA disease activity, lower bone mineral density, and increased falls and fractures. Therefore, early screening of sarcopenia in RA patients is important to incorporate into clinical rheumatology practice.

P068 The effects of exercise and physical activity in inflammatory rheumatic diseases: a scoping literature review

Abstract Background/Aims Physical activity and exercise for the management of inflammatory rheumatic diseases is well described in the literature and is recommended in the EULAR 2018 physical activity and 2021 self-management guidelines. However, the extent to which physical activity and exercise is beneficial or detrimental in these patients is unclear. The aim of this review is to critically appraise the effects of physical activity and exercise interventions on patient-centred outcomes in a range of inflammatory rheumatic diseases in order to help guide clinical practice. Methods Pre-defined search terms were used to identify randomised controlled trials or systematic reviews published in English, studying any form of physical activity/exercise interventions for inflammatory rheumatic diseases. This included seronegative spondyloarthritis (including axial/psoriatic/enteropathic/reactive arthritis), rheumatoid arthritis, and broadly grouped connective tissue diseases including systemic lupus erythematosus, systemic sclerosis and myositis. Databases included MEDLINE via PubMed, CINAHL, Embase and Cochrane Database of systematic reviews from January 2018 onwards. Quantitative data regarding types of physical activity, any primary or secondary outcome measures and the quality of the evidence was compiled independently by two authors. 427 studies were identified and screened of which 160 were included in the final analysis. Results Numerous benefits of various quality in a range of physical activities across the diseases were identified. Interventions included swimming, aquatic exercises, global posture retraining and land based aerobic exercises (including walking, Nordic walking, Pilates, Tai Chi and High Intensity Interval Training). In terms of high-quality evidence, for seronegative spondyloarthritis, benefits were found for functional outcome scores, fatigue levels and disease activity scores. In rheumatoid arthritis, benefits were seen in fitness, disease activity scores, quality of life, muscle strength and pain reduction. Across the studied connective tissue diseases, benefits were seen in fitness, ability to carry out activities of daily living, muscle strength and fatigue. Low to moderate quality evidence for improvement was seen across all diseases in areas such as mood, sleep quality and flexibility/stiffness. However, there was significant heterogeneity amongst the dose and type of exercise interventions used between identified studies. This therefore precluded a meta-analysis which meant that this review was unable to recommend one specific exercise over another. Importantly, no adverse outcomes to physical activity were found in any of the identified studies. Conclusion It is evident that a range of exercise and physical activity interventions can have an important role in the management of inflammatory rheumatic diseases. Moreover, the wider well-established benefits of physical activity seen in the general population, including those of mental wellbeing and in cardiovascular disease, may be pertinent to the comorbidities associated with inflammatory rheumatic diseases. Future research would benefit from comparing doses and types of exercise interventions against each other in order to help further guide clinical practice. Disclosure R. Amarnani: None. M. Hadjidemetriou: None. A. Mundell: None. S. Katti: None. F. Chiwah: None. K. Ainsworth: None. G.S. Metsios: None. C. Lester: None.

P035 Patient-reported outcome measures for rheumatoid arthritis disease activity: using Rasch measurement theory to achieve more meaningful measurement

Abstract Background/Aims Disease activity (DA) monitoring is a standard of care in rheumatoid arthritis (RA), and there is demand for achieving this through patient-reported outcome measures (PROMs). A systematic review of PROMs for RA DA following COSMIN guidelines demonstrated a lack of sufficient evidence for content validity for the 10 existing PROMS, thus none could be recommended for use. The aim of this study was to use Rasch measurement theory (RMT) to develop a valid item pool for measurement of DA in RA. Methods Paper questionnaires were sent to people aged 18 or over with RA from four South Wales University Health Boards between September 2020 and November 2021. The questionnaire included 268 individual RA DA items extracted from the 10 PROMs identified by the systematic review, another four PROMs and a non-measurement group of items. Further items suggested by patient feedback were incorporated, including a Pain Activity Scale, discomfort when walking, standing, and exercising, plus fear of falling when walking. Items were grouped into domains established by OMERACT: tenderness and swelling, patient global, pain, fatigue, physical functioning; and additionally stiffness, swelling, discomfort/fear and mood. Exploratory factor analyses (EFA) were used to indicate which items from which domains loaded onto factors together. For each separate domain, psychometric properties were assessed by RMT analyses. This provided results on targeting, model fit, internal consistency, local dependency, unidimensionality and item threshold ordering. Results A test dataset of n = 398 and a validation dataset of n = 293 were available. EFA of the test dataset showed that 30 items from across the tenderness and swelling, patient global, pain, fatigue, physical functioning and stiffness domains loaded together. RMT analyses of these items in the test dataset indicated that the patient global domain comprised two distinct domains, which followed a clear content difference of general health and disease activity items. In assessing the best items to measure the now 7 domains, 12 items were discarded. These 7 domains were confirmed in the validation data. Subtest analyses indicated that patient global general health and fatigue did not measure the same overall construct as the other 5 domains, and instead worked together to measure a separate construct. This structure was confirmed using bi-factor model confirmatory factor analyses in the validation data. Conclusion Patient global items relating to general health and disease activity were two separate domains. RA DA can be measured using tenderness and swelling, patient global disease activity, pain, physical functioning and stiffness items, whilst fatigue and patient global general health items measure a health-related quality of life construct. The next steps are to undertake cognitive interviews to establish content validity and to develop a computer adaptive test based on anchored locations calculated using these data. Disclosure T. Pickles: None. M. Horton: None. K.B. Christensen: None. R. Phillips: None. D. Gillespie: None. N. Mo: None. E. Choy: None.

Tocilizumab-related hypertriglyceridemia is independent of key molecules regulating lipid metabolism.

Tocilizumab (TCZ) treatment is associated with dyslipidaemia, including a rise in triglycerides through a mechanism poorly understood. Three molecules play key roles in the regulation of triglyceride metabolism: apolipoprotein C-III (ApoC-III), angiopoietin-like protein 4(ANGPLT4) and lipoprotein lipase (LPL). The aim of this work was to analyse whether the changes in triglycerides shown by TCZ-treated RA patients could stem from the dysregulation that can occur in these regulatory molecules. Twenty-seven RA patients included in the TOCRIVAR study who received TCZ (8 mg/kg IV/q4w) were evaluated at baseline and at Weeks 12, 24 and 52 of treatment. ANGPTL4, ApoC-III and LPL, a complete lipid profile and RA disease activity, were analysed at baseline and at each visit. Multivariable linear mixed models were performed to study changes over time in lipids and regulatory molecules. After 24 weeks of TCZ treatment, HDL cholesterol, apolipoprotein A1 and triglycerides increased, whereas lipoprotein (a) decreased significantly from baseline values. However, 1 year after TCZ, no significant differences in lipid pattern were observed with respect to baseline. Serum ANGPTL4 and Apo-CIII levels decreased gradually over time, both being significantly lower than baseline values at Week 52. LPL concentration did not change significantly during TCZ treatment. Remarkably, the elevation of triglycerides at Week 24 maintained its statistical significance after adjusting for the changes in ApoC-III, ANGPTL4 and LPL. In TCZ-treated RA patients basal serum levels of ANGPLT4 and ApoC-III, but not LPL, decreased significantly. However, the elevation of triglycerides after TCZ was not related to changes in these regulatory molecules.

Disease Activity and Health-Related Quality of Life Among Patients With Rheumatoid Arthritis With Different Alcohol Consumption Habits.

Multiple studies have found a relationship between alcohol consumption and disease activity in rheumatoid arthritis (RA), although reverse causation has been suggested to explain the association. We aimed to study the relationship between alcohol consumption and disease activity, disease progression, and health-related quality of life in patients with RA. We followed up 1,228 patients with newly diagnosed RA from a population-based case-control study, Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Drinkers and non-drinkers were compared to evaluate risk of unfavorable outcomes regarding disease activity and health-related quality of life. Odds ratios with 95% confidence intervals were calculated using logistic regression models. Non-drinkers at baseline had higher disease activity and estimated their pain as more severe compared to drinkers. At 1 year of follow-up, non-drinkers reported higher swollen and tender joint counts and experienced more pain and fatigue, lower global health scores, and lower health-related quality of life. The inverse relationship between alcohol consumption and RA-specific outcomes was also observed when comparing drinkers and non-drinkers who had not changed their alcohol consumption habits at or after the year of disease onset. Those who stopped drinking postbaseline experienced higher disease activity, more pain, and lower health-related quality of life at 1 year of follow-up, compared to drinkers, although there was no difference in disease activity at baseline between drinkers who continued versus discontinued drinking. Our findings argue against bias due to reverse causation. Alcohol consumption was associated with lower disease activity and higher health-related quality of life in RA patients in a dose-dependent manner.

Vitamin D deficiency in rheumatoid arthritis patients of India - a single-arm meta-analysis.

Vitamin D deficiency is commonly seen in patients with rheumatoid arthritis (RA). This meta-analysis is aimed to determine the prevalence of Vitamin D deficiency in RA patients in India and also to evaluate the association between vitamin D level and disease activity. The relevant works of literature were identified through multiple databases and data was extracted from eligible studies independently. A single-arm meta-analysis was performed to estimate the prevalence of Vitamin D deficiency in RA patients in an Indian setup and its association with disease activity. A total of 15 studies was included in the analyses. The mean serum vitamin D level was 19.99 ng/ml [95% CI 16.49-24.23]. The proportion of patients with low vitamin D level was 0.80 [95% CI 0.65- 0.90], Vitamin D deficiency was 0.56 [95% CI 0.31-0.77] and vitamin D insufficiency was 0.20 [95% CI 0.12- 0.32]. A negative relationship was seen with serum vitamin D and disease activity score. The results demonstrate significant low levels of serum vitamin D levels in patients with RA and established a negative correlation of Vitamin D with RA disease activity. The current evidence suggests a rationale for Vitamin D supplementation in the management of RA.

Impact of the COVID-19 pandemic on patients with rheumatoid arthritis: data from the Ontario Best Practices Research Initiative (OBRI).

The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with RA. We examined the potential impact of the pandemic on patient-reported outcomes (PROs), disease activity and medication profiles, comparing the periods pre-pandemic and during the pandemic. Patients enrolled in the Ontario Best Practices Research Initiative were included if they had at least one visit to a physician or study interviewer within 12 months before and after the start of pandemic-related closures in Ontario (15 March 2020). Baseline characteristics, disease activity, PROs [i.e. health assessment questionnaire disability index, RA disease activity index (RADAI), European quality of life five-dimension questionnaire], medication use and changes were included. Student's paired two-sample t-tests and McNamar's tests were performed for continuous and categorical variables between time periods. The sample for analysis consisted of 1508 patients, with a mean (s.d.) age of 62.7(12.5) years, and 79% were female. Despite decreases in the number of in-person visits during the pandemic, there was no significant negative impact on disease activity or PRO scores. The DASs in both periods remained low, with either no clinically significant differences or slight improvement. Scores for mental, social and physical health were either stable or improved. There were statistically significant decreases in conventional synthetic DMARD use (P < 0.0001) and increased Janus kinase inhibitor usage (P = 0.0002). Biologic DMARD use remained stable throughout the pandemic. In this cohort, disease activity and PROs of RA patients remained stable during the COVID-19 pandemic. The longer-term outcomes of the pandemic warrant investigation.

Moringa Oleifera Extract Decreases Interleukin 6 Levels and Disease Activity in Rheumatoid Arthritis Patients

Moringa oleifera (MO) has anti-inflammatory, anti-arthritis, and immunosuppressant effects in Rheumatoid Arthritis (RA). This study aims to determine the effect of moringa oleifera extract on interleukin 6 levels and disease activity in RA. This research, with 30 patients, was divided into two groups: the intervention and the placebo. The intervention group received 40.50 mg/kg BW/day of Moringa oleifera extract for one month. IL-6 levels and SDAI scores were measured before and after the treatment. Paired t-test showed that IL-6 levels (p=0.070) and SDAI Scores (p=0.142) before and after MO administration for the control group were not significantly different (p&gt; 0.05). Paired t-test IL-6 (p=0.001) and SDAI Scores (p=0.001) before and after giving MO to the treatment group decreased significantly (p &lt;0.05). Independent t-test shows that the two changes, Delta-IL6 (p=0,008) and Delta-SDAI (p=0,017), are significantly different (p&lt;0.05). Moringa Oleifera Extract decreases IL-6 Levels and SDAI Scores in RA Patients. Bangladesh Journal of Medical Science Vol. 22 No. 02 April’23 Page : 416-421

The pleiotropic effects of statins in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease. Studies over the past two decades suggest that statins have a beneficial impact on the complications associated with RA. These complications include RA disease activity and risk for cardiovascular diseases (CVD). This review aims to discuss the efficacy of statin therapy in RA. The current evidence suggests that statins' immunomodulatory and antioxidant properties significantly reduce disease activity and inflammatory response in patients with RA. In RA patients, the risk of CVD is reduced by statin treatment, and statin discontinuation is associated with an increased cardiovascular disease risk. The combined effect of statins on improving vascular function, lowering lipid levels, and reducing inflammation in RA patients is responsible for the decreased all-cause mortality in statin users. Further clinical studies are needed to ensure the therapeutic efficacy of statins in patients with RA.

The Impact of Early Optimization of Infliximab Blood Concentrations &gt;1 μg/mL on Therapeutic Effectiveness in Rheumatoid Arthritis

Infliximab is a human-murine chimeric monoclonal IgG antibody against tumor necrosis factor that is used in combination with methotrexate for the treatment of moderate to severe rheumatoid arthritis (RA). The trough concentration of serum infliximab required to control disease activity in RA is ≥1 μg/mL, and we investigated whether this trough concentration can predict the effectiveness of RA treatment. We retrospectively analyzed the cases of 76 patients with RA. The REMICHECK Q® (REMIQ) is a kit that can check for serum infliximab concentrations. Infliximab concentrations >1 μg/mL at 14 weeks after an initial infliximab induction is considered REMIQ-positive, otherwise considered REMIQ-negative. Here, we determined the retention rates and investigated the clinical and serologic features of REMIQ-positive and REMIQ-negative patients. At 14 weeks, significantly more of the REMIQ-positive patients (n = 46) were responders compared to the non-responders (n = 30). The retention rate at 54 weeks was also significantly higher in the REMIQ-positive group versus the negative group. After 14 weeks, more patients in the REMIQ-negative group were considered inadequate responders, and their infliximab doses were escalated. At baseline, the REMIQ-positive group had significantly lower C-reactive protein (CRP) levels compared to the negative group. Cox regression analysis with multiple variables showed that the positivity of REMIQ (hazard ratio [HR] 2.10 and 95% confidence interval [CI]: 1.55-5.71) at baseline was associated with the achievement of low disease activity. The positivities of rheumatoid factor and anti-CCP antibody at baseline were associated with the achievement of remission with infliximab treatment (HR 0.44, 95% CI: 0.09-0.82 and HR 0.35, 95% CI: 0.04-0.48, respectively). The results of this study suggest that the control of RA disease activity may be facilitated by using the REMIQ kit at 14 weeks to check whether it is necessary to increase a patient's infliximab dose to ensure a therapeutic blood concentration that will help the patient achieve low disease activity.

Elevated serum soluble CD27 levels are associated with both disease activity and humoral immune activity in patients with rheumatoid arthritis.

To investigate the serum level of soluble CD27 (sCD27) and its potential clinical significance in rheumatoid arthritis (RA). Serum sCD27 levels in RA patients, idiopathic inflammatory myopathy (IIM) patients, systemic lupus erythematosus (SLE) patients and healthy controls (HCs) were detected by enzyme-linked immunosorbent assay. The medical information and laboratory data of the patients were collected. Serum sCD27 levels in RA patients with different clinical features were analysed, as was the correlation between the clinical data and serum sCD27 levels. Independent samples t test, the Mann-Whitney U-test or Wilcoxon signed-rank test, and Spearman correlation were used for statistical analysis. Levels of sCD27 were elevated in RA patients (3898 [2525, 5834] pg/mL) compared with IIM patients (2467 [1939, 3324] pg/mL) or HCs (1659 ± 648 pg/mL) (p 0.001). In addition, serum sCD27 levels correlated with age, erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A, immunoglobulin G, complement 4 and disease activity score in 28 joints in RA patients. Levels of sCD27 were higher in RF-positive RA patients (6054 ± 5842 pg/mL) than in RF-negative patients (3902 ± 2098 pg/mL), and a similar finding was also observed in anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (5810 ± 5671 pg/mL) and anti-CCP-negative (4183 ± 2187 pg/mL) RA patients. Serum ESR, RF, IgA, IgG levels and DAS28-CRP were elevated in RA patients with higher sCD27 levels than in those with lower sCD27 levels (p<0.01). Serum sCD27 might be a promising biomarker that reflects both disease activity and humoral immunity activity in RA.

Patients with ACPA-positive and ACPA-negative rheumatoid arthritis show different serological autoantibody repertoires and autoantibody associations with disease activity

Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as ACPA-positive (ACPA+) or ACPA-negative (ACPA−), respectively. In this study, we aimed to elucidate a broader range of serological autoantibodies that could further explain immunological differences between patients with ACPA+ RA and ACPA− RA. On serum collected from adult patients with ACPA+ RA (n = 32), ACPA− RA (n = 30), and matched healthy controls (n = 30), we used a highly multiplex autoantibody profiling assay to screen for over 1600 IgG autoantibodies that target full-length, correctly folded, native human proteins. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA− RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies with significantly higher abundances in ACPA+ RA patients and ACPA− RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons; this provides further evidence of immunological differences between these two RA subgroups despite sharing similar symptoms. On the other hand, we identified 30 and 25 autoantibodies with lower abundances in ACPA+ RA and ACPA− RA, respectively, of which 8 autoantibodies were common in both comparisons; we report for the first time that the depletion of certain autoantibodies may be linked to this autoimmune disease. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with Clinical Disease Activity Index, but associate differently depending on patients’ ACPA status. In all, we present candidate autoantibody biomarker signatures associated with ACPA status and disease activity in RA, providing a promising avenue for patient stratification and diagnostics.

Use of some bone-related cytokines as predictors for rheumatoid arthritis severity by neural network analysis

Background. Rheumatoid arthritis (RA) is characterized by synovial membrane inflammation that results in joint damage. Many earlier studies have measured cytokines for a better diagnosis of RA. In the present study, three bone biomarkers [osteopontin, stromelysin-1 (MMP3), and vascular endothelial growth factor-A (VEGF)] are examined for their ability to estimate the severity of disease by using artificial neural network (NN) analysis and binary logistic regression analysis. Methods. The study enrolled 87 RA patients and 44 healthy control subjects. The biomarkers were measured by the enzyme-linked immunosorbent assay technique. Disease Activity Score (28 joints) and C-reactive protein (CRP) (DAS28-CRP) was calculated by using DAS28-CRP calculator. The patients with DAS28-CRP 5.1 are considered as having high disease activity (HDA). While patients group with DAS28-CRP 5.1 are considered as moderate disease activity (MDA). The neural network (NN) analysis was used for the differentiation between groups. Results. Results showed that the most sensitive predictor for high disease activity (HDA) of RA is MMP3, followed by osteopontin and VEGF. These three biomarkers can differentiate significantly between HDA and MDA with a relatively high size effect (Partial 2 = 0.323, p 0.001). The HDA group has a significantly higher MMP3, CRP, RF, and anti-citrullinated protein antibodies (ACPA) than the MDA group. MMP3 is strongly associated with two inflammatory indicators; CRP and ESR. Conclusion. There was a significant elevation in the serum level of MMP3 in RA patients with HDA compared to the MDA and control groups. High DAS28, RF, CRP, and ACPA were found in HDA patients compared with the MDA group. The use of the NN analysis indicated that the measured biomarkers help predict the HDA state in RA patients. MMP3 and osteopontin are diagnostic biomarkers for the severity of RA and are related to many disease-related characteristics with a sensitivity of 88.9% and specificity of 68.4%.

CircRNA_17725 Promotes Macrophage Polarization towards M2 by Targeting FAM46C to Alleviate Arthritis.

Accumulating studies have implicated that circular RNAs (circRNAs) play vital roles in the pathogenesis of rheumatoid arthritis (RA). Dysregulation of macrophage polarization leads to immune homeostatic imbalance in RA. However, the altering effects and mechanisms of circRNAs on macrophages polarization and immune homeostatic balance remain largely unclear. We aimed to investigate the potential role of circRNA_17725 in RA. The high-throughput sequence was performed to identify the dysregulated circRNAs in RA. We confirmed the data by CCK-8, EdU, and Annexin V/PI staining to elucidate the proliferation and apoptosis. The expressions of M1/M2-associated markers were confirmed using real-time PCR and flow cytometry analysis. Luciferase reporter assay and RNA Binding Protein Immunoprecipitation (RIP) were used to demonstrate the underlying mechanism of circRNA_17725. The altering effect of circRNA_17725 on macrophages in vivo was evaluated using collagen-induced arthritis (CIA) mouse model. circRNA_17725 was demonstrated to be downregulated in peripheral blood mononuclear cells and CD14+ monocytes from RA cases in contrast to healthy controls. The negative association between circRNA_17725 and the disease activity indexes (CRP, ESR, and DAS28) was observed, suggesting a vital role of circRNA_17725 in RA disease activity. Besides, after a coexpression analysis based on high-input sequencing and the bioinformatics analysis in MiRanda and TargetScan databases, a circRNA_17725-miR-4668-5p-FAM46C competing endogenous RNA (ceRNA) network was hypothesized. A series of cytology experiments in vitro have implicated that circRNA_17725 could inhibit the proliferation but enhance the apoptosis of macrophages. Decreased expression of TNF-α, IL-1β, and MMP-9 were observed in the supernatant of circRNA_17725-overexpressed Raw264.7 macrophages, implicating the inhibitory effect of circRNA_17725 on macrophage inflammatory mediators. Furthermore, circRNA_17725 could promote macrophage polarization towards M2 by targeting miR-4668-5p/FAM46C as a miRNA sponge. Additionally, circRNA_17725-overexpressed macrophages alleviated arthritis and protected against joint injuries and bone destruction by inducing macrophage polarization towards M2 in collagen-induced arthritis (CIA) mice. This study has suggested that circRNA_17725 regulated macrophage proliferation, apoptosis, inflammation, and polarization by sponging miR-4668-5p and upregulating FAM46C in RA.

Clinical characteristics of flares in patients with rheumatoid arthritis after total hip and total knee arthroplasty.

Clinical characteristics of flares in patients with rheumatoid arthritis after total hip and total knee arthroplasty.

Clinical evaluation of optical spectral transmission imaging for detection of disease activity in rheumatoid arthritis

Objective To investigate the performance and factors of influence of optical spectral transmission (OST) imaging as a new technique for measuring joint inflammation in rheumatoid arthritis (RA). Method OST was performed in 24 RA patients and 37 controls. Mann–Whitney U-test was used to assess differences in OST score between RA patients and controls. Receiver operating characteristics (ROC), linear regression and generalized estimating equations analysis were used to assess the discriminative capability of OST and the association of OST score with clinical disease parameters, ultrasound, radiographic features and cardiovascular risk parameters. Results Median OST score was higher in RA patients than in controls [16.9 (interquartile range 12.77–19.7) vs 12.11 (10.32–14.93)]. At patient level, OST score was moderately associated with ultrasound [beta 0.38 (95% CI 0.16–0.60), p = 0.001] and clinical disease activity [28-joint Disease Activity Score–C-reactive protein beta 0.30 (95% CI 0.04– 0.57), p = 0.024] in RA patients. In controls, male sex, high body mass index, and hypertension were associated with higher OST scores, while these associations were absent in RA. At joint level, the area under the ROC curve for OST score, with ultrasound or clinical swelling as reference, ranged from 0.63 to 0.70. Joint-space narrowing and malalignment were associated with higher OST joint scores, and subchondral sclerosis with lower scores. Conclusion OST provides an objective measure of synovitis and correlates moderately with other examined disease activity assessment tools. Clinical patient characteristics must be considered when interpreting the results.

High Levels of Leptin and Adipsin Are Associated with Clinical Activity in Early Rheumatoid Arthritis Patients with Overweight and Periodontal Infection.

Adipokines are associated with the pathogenesis of rheumatoid arthritis (RA) and are potential biomarkers of disease activity, periodontitis, and obesity. The aim of this was to establish the association between adipokine profile, RA disease activity, body mass index, and periodontal infection. This study evaluated 51 patients with early-RA and 51 controls including serum rheumatological markers, adipokine levels, detection of Porphyromonas gingivalis and serum anti-Porphyromonas gingivalis antibodies, clinical and periodontal measurements. Statistical analyses were run with SPSS® V26, with a logistic regression model to confirm associations. The results show high levels of leptin were more frequent in patients (p = 0.001) who simultaneously showed a higher frequency of Porphyromonas gingivalis (p = 0.004). Patients with concomitant presence of Porphyromonas gingivalis, high clinical activity score, and overweight were correlated with high levels of leptin (OR, 7.20; 95% CI, 2.68-19.33; p = 0.0001) and adipsin (OR, 2.69; 95% CI, 1.00-7.28; p = 0.005). The conclusion is that high levels of leptin and adipsin are associated with greater clinical activity in early-RA patients with overweight and periodontal infection, whereby overweight and Porphyromonas gingivalis may enhance RA activity. This may represent a pathological mechanism between these conditions, where adipokines seem to have a key role.