Browse

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

ID PMID Title PublicationDate abstract
33228136 Deimination, Intermediate Filaments and Associated Proteins. 2020 Nov 19 Deimination (or citrullination) is a post-translational modification catalyzed by a calcium-dependent enzyme family of five peptidylarginine deiminases (PADs). Deimination is involved in physiological processes (cell differentiation, embryogenesis, innate and adaptive immunity, etc.) and in autoimmune diseases (rheumatoid arthritis, multiple sclerosis and lupus), cancers and neurodegenerative diseases. Intermediate filaments (IF) and associated proteins (IFAP) are major substrates of PADs. Here, we focus on the effects of deimination on the polymerization and solubility properties of IF proteins and on the proteolysis and cross-linking of IFAP, to finally expose some features of interest and some limitations of citrullinomes.
30927515 Assessing Rheumatoid Arthritis Disease Activity With Patient-Reported Outcomes Measurement 2020 Apr OBJECTIVE: Health information technology has enabled efficient measurement of patient-reported outcomes (PROs). The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) is becoming more widely adopted for research and routine care, and some PROMIS instruments might be substituted for lengthier, legacy PRO instruments. METHODS: Four PROMIS computer-adaptive testing (CAT) instruments (pain interference, physical function, sleep disturbance, and fatigue) and the Routine Assessment of Patient Index Data 3 (RAPID3), along with pain intensity and patient global assessment score, were administered to participants in the ArthritisPower registry. The RAPID3 was predicted using different combinations of these variables to create a new score (CAT-PROMIS RAPID3). Kappa statistics and Bland-Altman 95% limits of agreement were used to measure agreement between the observed versus predicted RAPID3. RESULTS: A total of 6,154 eligible patients contributed 11,275 observations. The mean ± SD age was 52.7 ± 10.5 years, and 93% of patients were women. The median assessment times ranged from 29 seconds (PROMIS sleep disturbance) to 116 seconds (RAPID3). As single pairwise comparisons, the PROMIS CATs examined were modestly correlated (r approximately 0.4-0.7) to one other and RAPID3. Together with the pain intensity and patient global assessment, the PROMIS instruments explained a high fraction of total variance (R(2) = 0.97) of the RAPID3 score. In the model with the highest agreement (κ = 0.93) between the observed RAPID3 and the CAT-PROMIS predicted RAPID3, Bland-Altman 95% limits of agreement showed minimal residual differences and no systematic biases. CONCLUSION: There was excellent agreement between the observed RAPID3 and predicted RAPID3 scores estimated using several PROMIS instruments. The Multidimensional Health Assessment Questionnaire and patient global assessment components of RAPID3 may be unnecessary if PROMIS scores are available.
33031458 The impact of functional medicine on patient-reported outcomes in inflammatory arthritis: 2020 BACKGROUND: Despite treatment advances for inflammatory arthritis, a significant amount of patients fail to achieve remission. Other modifiable factors such as diet, physical activity and environmental exposures may be an important area of focus to help patients achieve disease remission and greater overall health. Functional medicine focuses on these lifestyle factors and may be an important adjunctive therapy. In this study, we examined the impact of functional medicine on patient-reported outcomes in patients with inflammatory arthritis. MATERIALS AND METHODS: In this 12-week, retrospective study, patients with confirmed diagnoses of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) were treated according to guidelines from the American College of Rheumatology for RA or PSA respectively. Those in the functional medicine group underwent a functional medicine program adjunctive to the standard of care. Patient reported outcomes, such as PROMIS (Patient Reported Outcomes Measurement Information System) global physical health, mental health and pain scores were collected at baseline and 12 weeks. Multivariable statistical modeling was used to identify the impact of functional medicine on patient-reported outcomes. RESULTS: 318 patients were screened and 54 patients (mean age 52.9±11.3 years, females 74(67.9%)), were included. Baseline characteristics were similar in both patient groups with the exception of PROMIS global physical health and pain (PROMIS global physical health score 43·2 ± 6·6 and 39·7 ± 8·7 and pain scores of 3·5 ± 1·9 and 5·2 ± 2·7 in the functional medicine group vs. standard of care group respectively). Using multivariable model to account for these differences, patients in the functional medicine group had a statistically significant reduction in pain (0.92, p-value = 0.007) and change in PROMIS physical health score (2·84, p-value = 0.001) as compared to the standard of care. Changes in PROMIS global mental health scores were also significant and were dependent on age and were greatest in those older than 55. LIMITATIONS: Retrospective design, baseline difference in patient reported outcomes. CONCLUSIONS: Functional medicine may have an important role as adjunctive therapy to improve patients' pain, physical and mental health in those who do not see improvement with conventional therapy alone.
31376089 Asymmetric and symmetric dimethylarginine concentration as an indicator of cardiovascular 2020 Jan Rheumatoid arthritis (RA) is the most common type of inflammatory arthritis leading to joint damage and physical disability. Cardiovascular diseases (CVDs) are considered a common comorbidity in patients with RA. However, the mechanism underlying its pathogenesis is not definitively explained. Endothelial dysfunction caused by impaired nitric oxide synthesis is an early indicator of cardiovascular disease. Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) the inhibitors of endothelial nitric oxide synthase (NOS) have emerged as novel CVD risk factor determiners. Concerning the unmet need to identify a salutary biomarker for CVD prediction, the purpose of this meta-analysis was to assess the serum/plasma ADMA and SDMA levels in RA patients compared with the healthy controls. A thorough literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar to identify all studies reporting ADMA and/or SDMA levels in RA patients compared with healthy controls. The quality of studies was evaluated using the Newcastle-Ottawa scale (NOS). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was used as the effect size in this study. We also conducted stratified analysis based on assay methods and median age of the participants. Fourteen articles were included. The pooled serum/plasma levels of ADMA were higher in RA patients compared with those of healthy controls (SMD = 1.02, 95% CI = 0.49 to 1.55); However, no statistical differences between RA patients and healthy controls in serum/plasma SDMA levels was seen (SMD = 0.57, 95% CI = -0.21 to 1.36). Subgroup analyses suggested that participants aged > 50 years had higher levels of ADMA rather than controls and the measurement method was a source of heterogeneity for ADMA. According to the results of this meta-analysis, ADMA measurement but not SDMA, can be useful for assessment of endothelial dysfunction as a predictor of CVD risk in RA patients. Prospero registration number: CRD42019121126.
32264972 Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk 2020 Apr 7 BACKGROUND: Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in the pathogenesis of rheumatoid arthritis. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signalling. The aim of this study was to compare the effects of sarilumab and adalimumab (a tumour necrosis factor alpha inhibitor) monotherapy on levels of circulating biomarkers associated with the acute-phase response, bone remodelling, atherothrombosis, anaemia of chronic disease and markers purported to reflect synovial lymphoid and myeloid cell infiltrates, as well as the potential of these biomarkers to differentially predict clinical and patient-reported outcomes with sarilumab vs. adalimumab. METHODS: In this post hoc analysis, serum samples were analysed at baseline and prespecified post-treatment timepoints up to week 24 in adults with moderate-to-severe active rheumatoid arthritis intolerant of or inadequate responders to methotrexate from the MONARCH trial (NCT02332590). RESULTS: Greater reductions in C-reactive protein (CRP; - 94.0% vs. -24.0%), serum amyloid A (SAA; - 83.2% vs. -17.4%), total receptor activator of nuclear factor-κB ligand (RANKL; - 18.3% vs. 10.5%) and lipoprotein (a) (- 41.0% vs. -2.8%) were observed at week 24 with sarilumab vs. adalimumab, respectively (adjusted p < 0.0001). Greater increases in procollagen type 1 N-terminal propeptide (P1NP) were observed with sarilumab vs. adalimumab at week 24 (22.8% vs. 6.2%, p = 0.027). Patients with high baseline SAA, CRP and matrix metalloproteinase-3 (MMP-3) were more likely to achieve clinical efficacy, including American College of Rheumatology 20% improvement criteria and Disease Activity Score (28 joints)-CRP < 3.2, and report improvements in patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and pain visual analogue scale, with sarilumab than adalimumab. CONCLUSION: Sarilumab was associated with greater positive effects on bone remodelling and decreases in biomarkers of the acute-phase response, synovial inflammation and cardiovascular risk vs. adalimumab. High baseline concentrations of SAA, CRP and MMP-3 are predictive of clinical and patient-reported outcome responses to sarilumab treatment and prospective validation is warranted to confirm these results. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02332590. Registered on 5 January 2015.
32944882 Bidirectional association between GERD and rheumatoid arthritis: two longitudinal follow-u 2021 Apr Several previous studies have suggested a relationship between GERD and RA. However, no study has investigated the bidirectional relationship between GERD and RA. This study aimed to evaluate the causal relationships between rheumatoid arthritis (RA) and gastroesophageal reflux disease (GERD). Participants aged ≥ 20 years old in the Korean Health Insurance Review and Assessment Service-National Sample Cohort from 2002 to 2013 were enrolled. In study I, 132,140 GERD participants were 1:2 matched with 264,280 control I participants. In study II, 6615 RA participants were 1:4 matched with 26,460 control II participants. Both control I and control II groups were matched with their study groups for age, sex, income, and region of residence. The occurrence of RA (study I) and GERD (study II) were followed up in both the study and control groups. The hazard ratios (HRs) of GERD for RA (study I) and of RA for GERD (study II) were analysed using stratified Cox-proportional hazards models. In study I, 0.8% (1,034/132,140) of the GERD group and 0.5% (1,290/264,280) of the control I group had RA (P < 0.001). The GERD group demonstrated a 1.49-fold higher adjusted HR than did the control I group (95% confidence interval (95% CI) = 1.37-1.62, P < 0.001). In study II, 22.5% (1,490/6,615) of the RA group and 15.2% (4,034/26,460) of the control II group had GERD (P < 0.001). The RA group showed a 1.46-fold higher adjusted HR than did the control II group (95% CI = 1.38-1.55, P < 0.001). GERD and RA have bidirectional associations in Korean adult population. Key Points • Several previous studies have suggested a relationship between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA). • However, no study has investigated the bidirectional relationship between GERD and RA. • This is the first study to present a bidirectional relationship between GERD and RA. • GERD and RA have bidirectional relations with each other.
32073519 Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloa 2020 Mar BACKGROUND: The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases. OBJECTIVES: The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs. METHODS: BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI). RESULTS: A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01-4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15-2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups. CONCLUSIONS: In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.
32250474 Effects of overweight and underweight on the treatment outcomes of rheumatoid arthritis pa 2020 Aug WHAT IS KNOWN AND OBJECTIVE: The effects of the body size condition (overweight and underweight) on the outcome of antirheumatic drugs are unclear. The aim of this study was to elucidate the relationship between body size and treatment outcomes in rheumatoid arthritis patients treated with biological antirheumatic drugs. METHODS: A retrospective observational descriptive study was conducted at Tokyo Women's Medical University, Medical Center East, from June 2015 to May 2018. Primary and secondary outcomes were defined as antirheumatic treatment ineffectiveness and antirheumatic treatment discontinuation due to any side effects, respectively. Multivariate logistic regression analysis was used to determine the risk factors for the outcomes and to calculate the odds ratio (OR) and the 95% confidence interval (95% CI). RESULTS AND DISCUSSION: A total of 297 patients were included. Primary and secondary outcomes were observed in 42 (14%) and 11 (4%) of the patients, respectively. Multivariate logistic regression analysis demonstrated that a body mass index (BMI) ≥25 kg/m(2) (OR = 4.22, 95% CI; 1.69-10.5, P = .002) was associated with rheumatoid arthritis treatment ineffectiveness and that BMI <18.5 kg/m(2) (OR = 5.87, 95% CI; 1.25-27.5, P = .025) and tacrolimus use (OR = 9.06, 95% CI; 1.37-60.1, P = .022) were associated with antirheumatic treatment discontinuation due to any side effects. The cut-off dose for tacrolimus was 0.5 mg/day. WHAT IS NEW AND CONCLUSION: Overweight affects antirheumatic drug efficacy. Underweight and tacrolimus use increased the discontinuation of antirheumatic drugs due to side effects. A validation study is needed to confirm the reliability of these results.
33178184 Non-Canonical WNT5A Signaling Through RYK Contributes to Aggressive Phenotype of the Rheum 2020 We hypothesized that WNT5A could contribute to the enhanced migration and invasiveness of rheumatoid arthritis fibroblast-like synoviocytes (RA FLS), which is one of the incompletely understood aspects of the RA FLS aggressive phenotype. This hypothesis is based on the previous evidence of a WNT5A role in both, RA and cell migration. Migration and invasion of RA FLS were assessed after incubation with recombinant Wnt5a (rWnt5a) or silencing of the endogenous WNT5A expression. The expression of WNT5A, WNT receptors, cytokines, chemokines, and metalloproteinases was quantified with RT-PCR. The WNT pathway was explored with gene silencing, antibody and pharmacological inhibition followed by migration assays and phosphoprotein western blots. Here, we reported that rWnt5a promoted migration and invasion of RA FLS, whereas knockdown of the endogenous WNT5A reduced them. These effects were specific to the RA FLS since they were not observed in FLS from osteoarthritis (OA) patients. Also, rWnt5a induced the expression of IL6, IL8, CCL2, CXCL5, MMP1, MMP3, MMP9, and MMP13 from baseline or potentiating the TNF induction, WNT5A signaling required the RYK receptor and was mediated through the WNT/Ca(2+) and the ROCK pathway. These pathways involved the RYK and ROCK dependent activation of the p38, ERK, AKT, and GSK3β kinases, but not the activation of JNK. Together these findings indicate that WNT5A contributes to the enhanced migration and invasiveness of RA FLS through RYK and the specific activation of ROCK and downstream kinases.
33026292 Increase in MEG3, MALAT1, NEAT1 significantly predicts the clinical parameters in patients 2020 Nov Aim: This study investigated deregulation of lncRNAs MEG3, MALAT1, NEAT1 and their associations with clinical parameters in rheumatoid arthritis (RA). Materials & methods: LncRNAs MALAT1, MEG3, NEAT1 were quantified from peripheral blood mono-nuclear cells (PBMCs) and plasma of 82 RA patients with 15 matched controls and from knee fluid of 24 RA patients with ten osteoarthritis controls. Multivariate analyses were performed among lncRNAs and clinical parameters of RA. Results: MALAT1, MEG3, NEAT1 were increased in PBMCs, plasma, synovial fluid (p < 0.05) of RA patients. Significant correlations were observed for MEG3 with TJC (r = 0.29), NEAT1 with TJC (r = 0.49), swollen joint count (r = 0.20), DAS28-CRP (r = 0.29). Multivariate analysis revealed that 48.5% of TJC and 31.5% of swollen joint count could be predicted by lncRNAs. Conclusion: The findings suggested that the lncRNAs might be explored as probable markers in monitoring disease activity.
32133564 Impact of Ramadan diurnal intermittent fasting on rheumatic diseases. 2020 Aug INTRODUCTION: Ramadan intermittent fasting is observed by Muslims from sunrise to sunset and alternated with moments of re-feeding. The aims of this study were to assess the impact of Ramadan fasting on rheumatoid arthritis (RA) and spondyloarthritis (SpA) activity and to assess its impact on chronic medications intake in patients with rheumatic diseases. METHODS: This prospective monocentric study included patients with RA or SpA who fasted during Ramadan of 2019. The disease activity and the managing of chronic medications were assessed and compared between two visits: the first one 6 months before starting Ramadan fasting and the second after fasting at least 7 days. RESULTS: Fifty-six patients were included: 36 with RA (average age 57.5 ± 10.9 years) and 20 with SpA (average age 47 ± 12.6 years). In the RA group, the Disease Activity Scores (DAS) 28 ESR, and DAS 28 CRP decreased after fasting respectively from 4.3 ± 1.3 to 3.5 ± 1.4 (p < 0.001) and from 3.4 ± 1.2 to 2.9 ± 1.3 (p = 0.001). In the SpA group, Ankylosing Spondylitis Disease Activity Scores (ASDAS) ESR and ASDAS CRP decreased respectively from 2.3 ± 0.5 to 1.9 ± 0.7 (p = 0.039) and from 1.9 ± 0.5 to 1.8 ± 0.8 (p = 0.388). Fasting did not affect significantly either compliance with chronic medications or tolerance. CONCLUSIONS: Fasting can be a possible way to induce rapid improvement of rheumatic diseases activity. In addition, patients with a specific fear of drug intake during this period can be reassured, which will enhance the adherence to treatment. Key Points • Fasting during Ramadan, the ninth month of the Islamic calendar, consists of intermittent fasting observed from sunrise to sunset. • In this set of patients, beneficial effects of intermittent fasting were demonstrated on RA activity, but were less evident in patients with SpA despite a general trend towards improvement. • Fasting did not affect significantly either compliance with chronic medications or tolerance.
30192341 The Effectiveness of Olive Oil in Controlling Morning Inflammatory Pain of Phalanges and K 2020 Mar/Apr PURPOSE: This study aimed to determine the effectiveness of olive oil in controlling morning inflammatory pain of phalanges and knees among women with rheumatoid arthritis. DESIGN: This is a randomized clinical trial, which was done in Arak, Iran. METHOD: After selecting 60 women based on a convenience sampling method, they were randomly allocated into five groups. A demographic questionnaire, the Visual Analogue Scale, and the Disease Activity Score 28 were completed. After 12 weeks of interventions, the last two scales were again completed. All data were analyzed using t test, Kruskal-Wallis test, and Friedman test. RESULTS: The mean age of the women was 40 ± 10.5 years. The result of the Friedman test showed a significant difference (p ≤ .001) among the total mean of groups before and after interventions. The post hoc test (least significant difference [LSD]) showed a significant difference (p ≤ .001) between the mean of Disease Activity Score 28 in the group using olive oil for massaging. Results also showed that there are significant differences (p ≤ .001) among the mean of Visual Analogue Scale rates, among the mean of the number of painful joints, and among the mean of the number of swollen joints after intervention in the five groups. CONCLUSION: Applying topical extra virgin olive oil, Piroxicam gel, and paraffin oil; dry massaging; and taking routine drugs alone were all effective in controlling rheumatic arthritis manifestations, respectively. Therefore, applying topical extra virgin olive oil for controlling of inflammatory pain of joints in rheumatic arthritis is recommended. CLINICAL RELEVANCE: In comparison with other medical ointments for RA, olive oil has lower expenditure and is findable in many homes.
32862311 Cognitive impairment in elderly patients with rheumatic disease and the effect of disease- 2021 Apr Recent development of biologic disease-modifying anti-rheumatic drugs (DMARDs) has led to better control of disease activity among patients with chronic rheumatological diseases. Many patients with rheumatic disease are living longer, adding to the growing elderly population. Rheumatic diseases, most notably rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are known to increase the risk of cognitive impairment. Systemic inflammation associated with chronic rheumatological diseases has been postulated to be key driver of cognitive decline. Recent development of classic and biologic DMARDs have led to better control of disease activity among patients with rheumatic conditions. It is proposed that strict control of systemic inflammation will significantly lower the risk of cognitive impairment among patients with rheumatic disease. The impact of classic DMARDs on cognitive function appears to be variable. On the other hand, biologic DMARDs, specifically antitumor necrosis factor (TNF) drugs (i.e., etanercept), have been shown to significantly lower the risk of dementia. Experimental studies on IL-1, IL-6, and B and T cell blockade are promising. However, clinical data is limited. Preclinical studies on targeted therapies, specifically JAK/STAT inhibitors, also show promising results. Additional studies are necessary to better understand the impact of these newer biologic agents on cognitive function in elderly patients with rheumatic disease. Key points • Patients with chronic rheumatic conditions are beginning to live longer, adding to the elderly population. • Patients with chronic rheumatologic disease are at increased risk of cognitive impairment compared to the general population. • Recent development of biologic (i.e., TNF, IL-1, IL-6) and targeted drugs (i.e., Janus kinase inhibitors) have led to better control of disease activity. • Current evidence suggests that TNF inhibitors may have beneficial effects on cognitive function. However, evidence on newer biologic and targeted therapies is limited.
32673817 Hsa_circ_0088036 promotes the proliferation and migration of fibroblast-like synoviocytes 2020 Sep Circular RNAs (circRNAs) have been demonstrated to play crucial roles in the development and progression of various types of cancers by serving as microRNA sponges to regulate the expression of target genes. Although in-depth studies of circRNAs have been conducted, their functional and pathological significance in autoimmune diseases, including rheumatoid arthritis (RA), remains unclear. Our previous study verified that hsa_circ_0088036 (circ0088036) is significantly elevated in peripheral blood mononuclear cells from patients with RA. The present study aimed to explore the roles of circ0088036 in the pathogenesis of RA. The circ0088036/miR-140-3p/silent information regulator 1 (SIRT 1) axis was predicted by bioinformatics tools. Circ0088036 was found to be aberrantly upregulated in fibroblast-like synoviocytes (FLSs) in RA compared with FLSs in osteoarthritis (OA). Functionally, upregulated circ0088036 promoted the proliferation and migration of RA-FLSs. Mechanistically, circ0088036 acted as a miR-140-3p sponge to upregulate SIRT 1 expression, subsequently promoting RA progression. In conclusion, this study revealed that circ0088036 may play an essential role in promoting synovial pathogenesis via the circ0088036/miR-140-3p/SIRT 1 axis in RA, providing new insight into circRNAs during RA progression.
32434463 Targeted drug-delivery systems in the treatment of rheumatoid arthritis: recent advancemen 2020 Apr Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that is characterized by synovial inflammation, cellular infiltration in joints which leads to progressive joint destruction and bone erosion. RA is associated with many comorbidities including pulmonary disease, rheumatoid nodules and can have a pessimistic impact on quality of life. The current therapies of RA treatment comprise conventional, small molecule and biological antirheumatic drugs. Their utility as therapeutic agents is limited because of poor absorption, rapid metabolism and adverse effects (dose-escalation, systemic toxicity, lack of selectivity and safety). To overcome these limitations, the novel drug delivery systems are being investigated. This review has compiled currently approved therapies along with emerging advanced drug-delivery systems for RA treatment. Further, active targeting of therapeutic agents to inflamed joints via folate receptor, CD44, angiogenesis, integrins and other provided an improved therapeutic efficacy in the treatment of RA.
33159095 Improved classification of rheumatoid arthritis with a score including anti-acetylated orn 2020 Nov 6 The presence of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) autoantibodies contributes to the current rheumatoid arthritis (RA) classification criteria. These criteria involve stratification on antibody levels, which limits reproducibility, and underperform in the RA patients without RF and anti-CCP. Here, we have explored if two anti-acetylated peptide antibodies (AAPA), anti-acetylated lysine (AcLys) and anti-acetylated ornithine (AcOrn), could improve the performance of the current criteria. The analysis was done in 1062 prospectively-followed early arthritis (EA) patients. The anti-AcOrn were more informative than the anti-AcLys, the conventional RA antibodies and the anti-carbamylated protein antibodies. The anti-AcOrn produced a classification that did not require antibody levels and showed improved specificity (77.6% vs. 72.6%, p = 0.003) and accuracy (79.0% vs. 75.8%, p = 0.002) over the current criteria. These improvements were obtained with a scoring system that values concordance between anti-AcOrn, RF and anti-CCP. No significant gain was obtained in sensitivity (80.2% vs. 78.8%, p = 0.25) or in improving the classification of the RA patients lacking RF and anti-CCP, although the anti-AcOrn ranked first among the analysed new antibodies. Therefore, the anti-AcOrn antibodies could contribute to the improvement of RA classification criteria by exploiting antibody concordance.
33028811 CircRNA_09505 aggravates inflammation and joint damage in collagen-induced arthritis mice 2020 Oct 7 A number of circular RNAs (circRNAs) have been implicated in rheumatoid arthritis (RA) pathogenesis; however, little is known about their function and hidden molecular mechanism in immune and inflammation regulation. We investigated the role and the underlying mechanism of circRNA_09505 in RA in this study. Real-time PCR and fluorescence in situ hybridization (FISH) are adopted to estimate the quantitative expression and localization of circRNA_09505 in macrophages. The altering effect of circRNA_09505 on inflammation is investigated in vitro and in vivo by use of macrophage cell models and collagen-induced arthritis (CIA) mice. Luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) are used to confirm the circRNA_09505/miR-6089 ceRNA network predicted by bioinformatics analysis. Compared with controls, the expression of circRNA_09505 is upregulated in peripheral blood mononuclear cells (PBMCs) from patients with RA. The proliferation and cell cycle are significantly promoted when circRNA_09505 is upregulated in macrophages, whereas knockdown of circRNA_09505 inhibits macrophage proliferation and cell- cycle progression. Besides, circRNA_09505 can act as a miRNA sponge for miR-6089 in macrophages, and promote the production of TNF-α, IL-6, and IL-12 through ceRNA mechanism. Moreover, AKT1 is a direct target of miR-6089. CircRNA_09505 can promote AKT1 expression by acting as a miR-6089 sponge via IκBα/NF-κB signaling pathway in macrophages. Most interestingly, knockdown of circRNA_09505 significantly alleviates arthritis and inflammation in vivo in CIA mice. These data support the hypothesis that circRNA_09505 can function as a miR-6089 sponge and regulate inflammation via miR-6089/AKT1/NF-κB axis in CIA mice.
32518420 The contribution from interleukin-27 towards rheumatoid inflammation: insights from gene e 2020 Aug We aimed to assess expression of genes encoding the heterodimeric IL-27 cytokine and constituent subunits of the Il-27 receptor in rheumatoid arthritis (RA), including in extra-articular, subcutaneous rheumatoid nodules. Comparing between nodules and joint synovia, significantly elevated expression of IL27A within nodules, and comparable IL27B expression, identified nodules as a significant source of IL-27 in RA. T-lymphocytes were the main source of IL27RA transcript, and IL27RA expression correlated with a number of plasma cytokines, as well as tissue TNF expression in both nodules and RA synovia. In synovia, correlations between IL27A, IL27RA IL17A and CD21L expression, and significantly elevated expression of the genes encoding IL-27, associated the presence of IL-27 with B cell-dominated synovial inflammation. Impact from nodule derived IL-27 on systemic or synovial inflammation in RA remains unknown and further study of these implications is required. Our study raises questions regarding the appropriate circumstances for the blockade or administration of IL-27 as a potential therapeutic adjunct in RA.
32871905 Efficacy predictors of a second tumor necrosis factor inhibitor in the treatment of rheuma 2020 Aug 28 To retrospectively evaluate initial tumor necrosis factor inhibitor (TNFi) failure patients for clinical predictors of response to a 2nd TNFi in our 4282 rheumatoid arthritis (RA) patient database.A cross-sectional retrospective manual chart review of the electronic health record (EHR) was performed on 322 "real world" RA patients who were prescribed 2 TNFis. Response to TNFi was determined by the treating provider who had real time Clinical Disease Activity Index (CDAI) scores to inform treatment decisions. Age, gender, body mass index (BMI), insurance provider, duration of disease, cyclic citrullinated peptide antibody (CCP) and rheumatoid factor (RF) positivity, concomitant disease modifying anti-rheumatic drug therapy, length of time between diagnosis and start of 1st and 2nd TNFi, transient efficacy of 1st TNFi (defined as response to TNFi at 3 months but later lost response), and reason for discontinuation of 1st TNFi were analyzed. A multivariable logistic regression model was used to model response to a 2nd TNFi.Response proportions to the 2nd TNFi were greater in females (161/223, 72.2% response female vs 41/75, 54.7% male, P < .01), those who began their 1st TNFi within 3 months of their RA diagnosis, and in RF+ patients (123/170, 72.4% response seropositive vs 66/110, 60.0% seronegative, P < .03). The higher female response rate was independent of age, BMI, and seropositivity.In RA patients who failed an initial TNFi, female patients and patients with RF+ were more likely to have a clinical response to a 2nd TNFi. In the absence of these predictors, stronger consideration for choosing a biologic with an alternative mechanism of action might be given when the 1st TNFi fails.
32712723 Is Axial Spondyloarthritis More Common Than Rheumatoid Arthritis? 2020 Jul 25 PURPOSE OF REVIEW: To discuss the disease incidence and prevalence rates of axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS) relative to those of rheumatoid arthritis (RA). RECENT FINDINGS: According to the most recently published systematic reviews, pooled prevalence estimates for RA are 0.38% in North America, and 0.21 to 0.25% in European subregions, while that of AS is 0.20% in North America and 0.25% in Europe. The estimated prevalence of axSpA has been reported to be approximately twice as common as AS in a study from the USA. This finding has also been supported by studies from northern Norway, central Italy, western Turkey, northern and southern regions of China, and rural Taiwan. These data suggest that axSpA, that encompasses AS, may be more prevalent than RA, at least in some countries. In general, higher occurrences of RA relative to AS have been noted worldwide, both in terms of incidence and prevalence. But axSpA, that encompasses AS, may be more prevalent than RA, at least in some countries. There is a need for concurrently run studies in the same population for a reliable comparison to establish occurrence of RA, AS, and axSpA. It is hoped that the implementation of the ICD-11 codes for axSpA will be helpful in determining a more accurate estimate of its incidence and prevalence.