Factor In Rheumatoid Arthritis Patients Research Articles

RBM25 is required to restrain inflammation via ACLY RNA splicing-dependent metabolism rewiring.

Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis. Here, we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis (RA). Among them, decreased expression of RNA binding motif protein 25 (RBM25) was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages. Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes (including Il1b, Il6, and Cxcl10) was coupled with histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac modifications as well as hypoxia inducible factor-1α (HIF-1α) activity. Furthermore, RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase (Acly) pre-mRNA, resulting in two distinct Acly isoforms, Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L was subjected to protein lactylation on lysine 918/995, whereas Acly S did not, which influenced its affinity for metabolic substrates and subsequent metabolic activity. RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform, enhancing glycolysis and acetyl-CoA production for epigenetic remodeling, macrophage overactivation and tissue inflammatory injury. Finally, macrophage-specific deletion of RBM25 led to inflammaging, including spontaneous arthritis in various joints of mice and inflammation in multiple organs, which could be relieved by pharmacological inhibition of Acly. Overall, targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.

Fatigue in rheumatoid arthritis patients: The status, independent risk factors, and consistency of multiple scales.

Fatigue is a common symptom that negatively affects the outcomes and functions of rheumatoid arthritis (RA) patients. This study aimed to assess the fatigue by two scales and validate their consistency, also to comprehensively evaluate fatigue-related risk factors in RA patients. In this case-control study, the fatigue of 160 RA patients and 60 healthy controls was evaluated by the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and the Chinese version of the Brief Fatigue Inventory (BFI-C). The 28-joint disease activity score using erythrocyte sedimentation rate of RA patients was assessed. The BRAF-MDQ and BFI-C scores were elevated in RA patients versus healthy controls (all p < .001). Interestingly, BRAF-MDQ global fatigue score positively correlated with BFI-C global fatigue score in both RA patients (r = .669, p < .001) and healthy controls (r = .527, p < .001); meanwhile, Kendall's tau-b test showed a high consistency between BRAF-MDQ and BFI-C global fatigue scores in RA patients (W = 0.759, p < .001) and healthy controls (W = 0.933, p < .001). Notably, higher education level (В = -4.547; 95% confidence interval: -7.065, -2.029; p < .001) and swollen joint count (В = 1.965; 95% confidence interval: 1.375, 2.554; p < .001) independently related to BRAF-MDQ global fatigue score; higher education level (В = -0.613; 95% confidence interval: -0.956, -0.269; p = .001) and clinical disease activity index (В = 0.053; 95% confidence interval: 0.005, 0.102; p = .032) independently linked with BFI-C global fatigue score. Fatigue commonly occurs in RA patients, which independently relates to education level and disease activity. Furthermore, BRAF-MDQ and BFI-C scales exhibit a high consistency in assessing fatigue.

Newly developed cardiovascular risk factors in rheumatoid arthritis patients initiating biologic treatment.

Rheumatoid arthritis (RA) is a risk factor (RF) for cardiovascular (CV) disease, a leading cause of mortality in RA patients. Consecutive records of RA patients with high disease activity screened upon biologic therapy initiation were reviewed between January 2001 and 2018. Patients with at least 6-month follow-up and baseline disease activity scores were enrolled (n = 353) and stratified into manifest CV disorder ("overt CVD"), any traditional CV risk factor ("atCVrisk") and no CV risk factor ("vlCVrisk") groups. Overall, mean (SD) patient age was 51.4 (±12.2) years, and 291 (82.4%) subjects were female. Median follow-up was 41.9 (IQR 18.6, 80) months. Overall, 89 (25.2%) individuals developed at least one new CV RF, of which 65 (18.4%) acquired one and 24 (6.8%) two or more. Incident lipid disorders (42, 11.9%), followed by hypertension (14, 4%), atrial fibrillation (17, 4.8%) and venous thromboembolism (VTE) (16, 4.5%), were common. Incident major adverse cardiac events (MACE) were not reported in the vlCVrisk group, in contrast to atCVrisk (n = 8, 4.2%) or overt CVD (n = 4, 18.2%). Age was a significant predictor of incident CV risk factor (HR 1.04, 95% CI: 1.02-1.07; p < 0.01). In age-adjusted analyses, only baseline body mass index (BMI) (HR 1.11, 95% CI: 1.04-1.18; p < 0.01), but not ever smoking (p = 0.93), male sex (p = 0.26), positive RF (p = 0.24), positive ACPA (p = 0.90), or baseline disease activity (p = 0.19), were independent predictor of incident CV risk factors. Patients with RA initiating biologics should be screened for cardiometabolic risk factors, especially at an older age. The presence of at least one risk factor may be linked to a worse long-term prognosis.

The impact of biologic agents on cardiovascular risk factors in patients with rheumatoid arthritis: A meta analysis.

The purpose of the study is to evaluate the effects of biologic therapy on cardiovascular risk factors in rheumatoid arthritis patients to determine its clinical efficacy. Relevant literature was systematically searched in PubMed, Embase, and Cochrane Library databases. Meta-analysis was conducted using standardized mean differences (SMDs) and 95% confidence intervals (CIs) to evaluate cardiovascular risk factors and atherosclerosis. Heterogeneity, sensitivity analysis, and publication bias were assessed. Statistical significance was set at P<0.05. The meta-analysis revealed that biologic treatment in RA patients was associated with decreased high-density lipoprotein cholesterol (HDL-C) levels compared to controls (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). Subgroup analysis based on treatment duration showed heterogeneity and a potential decrease in total cholesterol levels after 12 months of treatment (MD = -0.03, 95% CI [-0.21, -0.15], P = 0.76). Biologic therapy significantly reduced triglyceride levels compared to controls (MD = -0.23, 95% CI [-0.37, -0.09], P = 0.001), as observed in subgroup analysis. Moreover, biologics effectively decreased low-density lipoprotein cholesterol (LDL-C) levels (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). However, biologic treatment was associated with increased inner carotid artery thickness (MD: 0.05, 95% CI: [0.03, 0.07], P<0.0001), indicating potential adverse effects on cardiovascular health. No significant effect on pulse wave velocity (PWV) was observed (MD: -0.23, 95% CI: [-0.80, 0.34], P = 0.43, I2 = 0%, P = 0.55). Biologic agents may improve lipid profiles in RA patients but could also have adverse effects on cardiovascular health. Further research is needed to comprehensively understand the impact of biologic therapy on lipid metabolism and cardiovascular outcomes in RA patients. https://www.crd.york.ac.uk/PROSPERO/, CRD42024504911.

Characteristics of depressive disorders in patients with rheumatoid arthritis and some related factors.

Rheumatoid arthritis (RA), a type of chronic arthritis, is common in Vietnam. It has severe consequences for patients, both physically and psychologically, including depressive disorders. Therefore, early detection of depressive disorders is of high importance to help provide comprehensive treatment and improve RA patients' quality of life. This cross-sectional study explored the prevalence of depressive disorders and their salient characteristics and related factors in RA patients in Vietnam. We enrolled 156 patients diagnosed with RA using the ACR-1987 criteria. The Patient Health Questionnaire-9 (PHQ-9) was used to screen for depressive disorders. Patients' demographic characteristics and clinical and laboratory investigation results, such as the visual analog score, complete blood count, erythrocyte sedimentation rate, Disease Activity Score 28 for RA with C-reactive protein (DAS28-CRP), and quality-of-life score (based on the SF-36 test) were analyzed. Depressive disorders assessed on the first day of admission were reevaluated by a psychiatrist if the PHQ-9 score was ≥ 5. According to the PHQ-9 results, depression prevalence among RA patients was 76.3%. The majority of patients (49.4%) had moderate-to-severe depression and 91% experienced sleep disorder symptoms. Negative thoughts -- suicidal ideation or self-injury - were reported by 21.8% of patients. Depression severity had a moderately positive relationship with disease activity level and a moderately negative relationship with quality of life. Depression prevalence was high among RA patients. Depression severity increased with disease activity and decreased quality of life.

Plasma Cholinesterase Activity in Patients With Rheumatoid Arthritis and Toxoplasmosis.

Background and objective Rheumatoid arthritis (RA) is a chronic autoimmune disease causing synovium inflammation and functional impairment. Toxoplasmosis is an intracellular zoonotic parasitic infection anda risk factor in immunosuppressed diseases including RA. The involvement of the cholinergic mechanism is not clear when both diseases exist in combination. This study aimed to examine plasma cholinesterase (ChE) activity in patients suffering from RA with concomitant toxoplasmosis, taking into account the enzyme susceptibility to in vitro inhibitory challenge with the organophosphate dichlorvos in RA patients. Methods This was a case-control study involving 88 RA patients and 61 healthy controls of both genders.The RA patients were allocated into three groups. The first group received no therapy (n=14), the second group received conventional anti-arthritis therapy (n=49), and the third group received conventional+biologic therapy(n=25). Plasma ChE activity was determined by an electrometric method. Plasma samples were screened for Toxoplasmagondii (T. gondii)infection, using ELISAT. gondii antibodies IgG andIgM.In vitro inhibition of plasma ChE activitywas assessed by incubating the samples with dichlorvos at0.25 and 0.5 μM.The time-dependent dichlorvos (0.25 μM)-induced plasma ChE inhibition and its kinetics weredetermined. Results The RA patients comprised 76 (86.4%) females and 12 males (13.6%), whereas healthy controls included 22 (36.1%) females and 39 (63.9%) males. The rates of toxoplasmosis IgG positivity in controls and RA patients were 26.2% and 39.8%, respectively. Plasma ChE activity in patients with RA was significantly higher than that in the control group, by 16%. Plasma ChE values of RA patients with conventional therapy and conventional + biologic therapy were higher than that of the control group, by 18% and 27%, respectively. Odds and risk ratios of elevated plasma ChE activity (20%) in RA patients with therapyindicated that high plasma ChE activity among RA patients with therapyis a risk factor. The plasma ChE activity of T. gondii IgG-positive RA patients was not significantly different from that of theIgG-negative ones. Dichlorvos at 0.25 and 0.5 μM significantly inhibited in vitro plasma ChE activity incontrols and RA patients. The rates of plasma ChE inhibition by dichlorvos were lower in the RA groups with conventional therapyin comparison with those in the control group (77% vs. 91%). Examining the dichlorvos time-dependent ChE inhibition kinetics, RA groups showed increases in the half-life of inhibition by 23.6% to 32.7% and the total inhibition time by 23.5% to 32.5%, together with decreases in the inhibition rate constant by 19% to 24.5%, an indication of reduced inhibition rate of plasma ChE activity compared to that of the control group. Conclusions The autoimmune nature of RA and its chronicity might have contributed to the increase in plasma ChE activity among the patients. This increase in enzyme activity could be a risk factor in RA patients undergoing conventional therapy alone or in combination with biologic therapy; however, the clinical significance of such a condition remains obscure at present. The in vitro inhibition of plasma ChE activity in RA patients suggests reduced susceptibility of the enzyme to ChE inhibition by dichlorvos. Toxoplasmosis was not a risk factor when plasma ChE activity was taken into account among RA patients.

“Assessment of potential drug-drug interactions and their associated risk factor in patients with rheumatoid arthritis: A cross-sectional study”

BackgroundRheumatoid arthritis patients poses high risk for the development of potential drug-drug interactions (PDDIs) due to polypharmacy. Data relating the assessment of PDDIs in rheumatoid arthritis patients is still limited. Therefore, we assessed the prevalence, severity and adverse events of PDDIs, and their risk factors in rheumatoid arthritis patients. MethodsA cross-sectional research was carried out for 36 months in a tertiary care teaching hospital. Patient who met study eligibility were enrolled and their drug therapies were reviewed thoroughly. Generic name of drug was entered into Micromedex® software to identify the PDDIs. Adverse events related to PDDIs were identified and subsequently managed. Logistic regression analysis was applied to identify the risk factors associated with PDDIs. ResultsOf 598 patients, 518 (86.6%) patients were presented with ≥1 PDDIs. A total of 1492 PDDIs were identified, and 43.1% were moderate in their severity. Corticosteroids (32.8%) was major class of drugs involved in PDDIs development. Aceclofenac plus prednisolone (7.9%) was most common drug pair involved in the development of PDDIs. About 2.7% adverse events related to PDDIs were found. Age and multiple comorbidities were the most common risk factors associated with PDDIs. ConclusionThe occurrence of PDDIs was high among rheumatoid arthritis patients, majority were moderate in their severity. Age and multiple comorbidities were the most common risk factors associated with development of PDDIs. Therefore, prescriber and pharmacists’ need to take urgent action in reviewing medications chart and subjected to identify PDDIs, and their associated risk factors to enhance drug safety.

CXCL9 and its Receptor CXCR3, an Important Link Between Inflammation and Cardiovascular Risks in RA Patients.

Cardiovascular disease (CVD) is the most common cause of mortality in rheumatoid arthritis (RA), and Inflammation has a decisive role in its pathogenesis. CXCL9 contributes to multi aspects of inflammatory reactions associated with the pathogenesis of CVD. In the current study, we evaluated the association of plasma CXCL9 and CXCR3 gene expression with Cardiovascular risk factors in RA patients for the first time. Thirty newly diagnosed, 30 on-treatment RA patients, and 30 healthy subjects were recruited in this study. The plasma concentration of CXCL9 and CXCR3 gene expression were measured using ELISA and Real-Time PCR, respectively. The CVD risk was evaluated using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE). The plasma levels of CXCL9 were significantly higher in the newly diagnosed and on-treatment RA patients compared to the control group (P < 0.0001 and P < 0.001, respectively). Also, The CXCR3 gene expression was strongly elevated in newly diagnosed and on-treatment patients (P < 0.001 and P < 0.01, respectively). The CXCL9 and CXCR3 were significantly associated with RA disease activity (P = 0.0005, r = 0.436; P = 0.0002, r = 0.463, respectively). The FRS was remarkably higher in newly diagnosed and on-treatment patients (P = 0.014 and P = 0.035, respectively). The CXCR3 gene expression significantly correlated with age, systolic blood pressure, FRS, and SCORE (P = 0.020, r = 0.298; P = 0.006, r = 0.346; P = 0.006, r = 0.349; P = 0.007, r = 0.341, respectively). The CXCL9 plasma concentration had a significant negative correlation with plasma HDL and LDL levels (P = 0.033, r = -0.275; P = 0.021, r = -0.296, respectively). CXCL9 and CXCR3 correlates with different variables of CVD in RA.

Renal function in patients with rheumatoid arthritis in Rafsanjan city in 2021

Renal involvement is one of the extra-articular manifestations of rheumatoid arthritis (RA). The current study aims to investigate renal function and its associated factors in RA patients. This cross-sectional study included 443 RA patients who were referred to Rafsanjan's only rheumatology clinic in 2021. Disease Activity Score 28 (DAS28) index was used to determine disease activity. Blood levels of creatinine, C-Reactive Protein test (CRP), Erythrocyte Sedimentation Rate (ESR), and urine analysis were also determined. Renal failure was classified based on Estimated Glomerular Filtration Rate (eGFR). SPSS.20 one-way ANOVA, Kruskal-Wallis test, the Mann-Whitney U test, and Chi-square were used to analyze the data. Patiens' mean age was 53.99 ± 12.34, and 85.8% (380 people) of the participants were female. Ther were 147 (33.2%) patients without renal failure, 260 (58.7%) with mild renal failure, and 36 (8.1%) with moderate/severe failure. Men had a 3.059 higher risk of renal failure than women (P = 0.001). The probability of developing renal failure in patients increased by 1.047 times with each year of age (P &lt; 0.001). As a chronic disease, RA can directly or through the use of disease medications and other risk factors, adversely affect other organs of the body, including the kidney. The current study's findings revealed a high prevalence of mild renal failure in these patients.

MicroRNA-345-3p is a potential biomarker and ameliorates rheumatoid arthritis by reducing the release of proinflammatory cytokines

ObjectivesThe study was to explore the influence of microRNA (miR)-345-3p on proinflammatory cytokines in patients with rheumatoid arthritis (RA).MethodsA total of 32 RA patients and 32 healthy patients were enrolled. Proinflammatory factors in patients’ serum were detected by ELISA, and miR-345-3p was detected by RT-qPCR. The correlation between miR-345-3p expression and proinflammatory factors in RA patients was analyzed. The diagnostic value of miR-345-3p and proinflammatory factors in RA patients was analyzed by receiver operating curve diagnosis. The predictive value of miR-345-3p levels and proinflammatory factors in RA patients was analyzed by multivariate Cox regression. HFLS-RA and HFLS cells were cultured, in which miR-345-3p and proinflammatory cytokines were detected by RT-qPCR. Cell proliferation and apoptosis were determined by CCK-8 and flow cytometry, respectively.ResultsMiR-345-3p was lowly expressed in the serum of RA patients. MiR-345-3p and proinflammatory factors were of diagnostic and predictive values in RA. Elevated miR-345-3p restrained the production of proinflammatory factors of HFLS-RA cells, improved cell proliferation, and reduced apoptosis.ConclusionMiR-345-3p is a potential biomarker and ameliorates RA by reducing the release of proinflammatory cytokines.

Prevalence of Latent Tuberculosis Infection (LTBI) in Mexican Patients With Rheumatoid Arthritis (RA).

Patients with rheumatoid arthritis (RA) are at increased risk of developing tuberculosis, and even more so if they receive biological agents. In Mexico, the prevalence of latent tuberculosis infection (LTBI) in RA diagnosed by interferon-gamma release assay (IGRA) is largely unknown. The objective was to determine LTBI prevalence and the associated risk factors in rheumatoid arthritis patients. A cross-sectional study was performed comprising 82 patients with RA who attended the rheumatology service at a second-level hospital. Demographic characteristics, comorbidity, Bacillus Calmette-Guerin (BCG) vaccination and smoking history, type of treatment, disease activity and functional capacity were investigated. The Disease Activity Score 28 and the Health Assessment Questionnaire-Disability Index were applied for the estimate of RA activity and functional capacity. Further information was compiled from the electronic medical records and personal interviews. LTBI was determined by QuantiFERON TB Gold Plus (QIAGEN, Germantown, USA). Prevalence of LTBI was 14% (95% confidence interval (CI): 8.6% to 23.9%). Factors associated with LTBI were history of smoking (odds ratio (OR) = 6.63 95% CI 1.01 to 43.3) and disability score (OR = 7.19 95%CI 1.41 to 36.6). The prevalence of LTBI in Mexican patients with RA was 14%. Our results suggest prevention of smoking and functional incapacity could reduce the risk of LTBI. Further research could endorse our results.

Adherence to treatment and associated factors in rheumatoid arthritis patients: a cross-sectional study from Iran.

The aim of this study is to evaluate adherence to treatment and its related risk factors among a sample of rheumatoid arthritis patients (RA) attending the rheumatology outpatient clinic of Kermanshah university of medical sciences. In this cross-sectional study, RA patients were asked to complete the Morisky questionnaire and 19-item compliance questionnaire for rheumatology (CQR). Patients were divided into two groups: adherent and non-adherent to treatment, based on the CQR questionnaire results. Demographic and clinical characteristics (age, sex, marital status, education level, economical condition, occupational status, place of residence, underlying diseases, type, and number of drugs) were compared between the two groups to investigate possible risk associations for poor adherence. 257 patients completed the questionnaires (mean age: 43.22, 80.2% female). 78.6% were married, 54.9% were housekeepers, 37.7% had tertiary education, 61.9% had moderate economic status, and 73.2% were residents of an urban area with a large population. Prednisolone was the most commonly used drug followed by non-steroidal anti-inflammatory drugs, sulfasalazine, hydroxychloroquine, and methotrexate. The mean score of the Morisky questionnaire was 5.528 (standard deviation=1.79). 105 patients (40.9%) were adherent to treatment based on the CQR questionnaire. High education level (college or university) was correlated with non-adherence to treatment [27 (25.71%) vs 70 (46.05%), p=0.004]. We concluded that the prevalence of non-adherence to treatment is 59.1% in rheumatoid arthritis patients in Kermanshah, Iran. Having a higher education level is a risk factor for poor treatment adherence. Other variables could not predict treatment adherence.

The genes expression status of inflammatory determinants following the oral administration of Mannuronic acid in patients with rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a progressive multifactorial inflammatory disorder. According to numerous evidence, pro-inflammatory markers such as TNF-a, IL-6, IL-22, MYD88 and TLR2 play a substantial role in the pathogenesis and persistence of this disease. B-D-Mannuronic acid (M2000) is a new immunosuppressive drug whose therapeutic effects have been approved in several clinical trials and the results of the phase III clinical trial of this drug in RA patients were potent and efficient. Therefore, the present investigation was designed to evaluate its anti-inflammatory effects on the expression of mentioned factors in RA patients. Material and methods: This research was carried out on 12 healthy individuals and 12 patients with RA and M2000 was administered to the patients orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected from the patients before and after treatment with M2000 to investigate the gene expression levels of TNF-a, IL-6, IL-22, MYD88 and TLR2 molecules in them using Real-time PCR. Results: This study data represented a higher gene expression in all target molecules in the RA patients in comparison to the healthy individuals. Furthermore, the outcomes showed that after 12 weeks of therapy with M2000, the gene expression levels of inflammatory factors TNF-a, IL-6, IL-22, MYD88 and TLR2 decreased significantly in treated patients compared to before therapy. The gene expression results were following the clinical and paraclinical assessments. Conclusion: In conclusion, M2000 as a newly approved anti-inflammatory and immunosuppressive drug, can be proposed as a therapeutic agent in RA patients.

Increased Circulating Pentraxin 3 Levels in Patients with Rheumatoid Arthritis: A Meta-analysis.

Pentraxin 3 (PTX3), a soluble pattern recognition molecule, not only acts as a promising indicator reflecting the disease activity of rheumatoid arthritis (RA) patients but exerts essential pathogenic roles in the progression of RA and serves as a potential therapeutic target for RA patients. Our study intends to systematically evaluate the circulating PTX3 levels and their potential influencing factors in RA patients. Articles regarding the circulating PTX3 levels of RA patients were identified in Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases. Standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were calculated and further illustrated by the forest plot. Egger's regression test and sensitivity analysis were conducted to assess the publication bias and stability of the results, respectively. Twenty articles with 21 individual studies were recruited in our meta-analysis. The overall results revealed that compared to healthy controls, RA patients had significantly higher circulating PTX3 levels (pooled SMD = 0.97, 95% CI: 0.48 to 1.45). Subgroup analyses further demonstrated that compared to healthy controls, RA patients of age ≤ 50 years, 2.6 < disease activity score in 28 joints (DAS28) ≤ 3.2, 3.2 < DAS28 ≤ 5.1, DAS28 > 5.1, C-reactive protein (CRP) levels > 10 mg/L, erythrocyte sedimentation rate (ESR) > 20 mm/h, and disease duration > 5 years had significantly higher circulating PTX3 levels, respectively; whereas RA patients of age > 50 years, DAS28 ≤ 2.6, CRP levels ≤ 10 mg/L, ESR ≤ 20 mm/h and disease duration ≤ 5 years had no significantly altered circulating PTX3 levels, respectively. Additionally, no matter whether the patients were of Caucasian ethnicity or not, circulating PTX3 levels were significantly increased in RA patients. Compared to healthy controls, circulating PTX3 levels are significantly increased in RA patients, which are influenced by age, disease activity, CRP levels, ESR, and disease duration.

Frailty in rheumatoid arthritis: A systematic review and meta-analysis.

Rheumatoid arthritis (RA) may cause damage to multiple organs and may further restrict the patient's physical, psychological and social functions. This meta-analysis aimed to explore the prevalence of frailty and prefrailty and the influential factors in RA patients. PubMed, Web of Science, Cochrane, Embase, and CNKI were searched to identify related articles. Articles published before July 23rd, 2021 that assessed frailty in patients with RA qualified for the systematic review and meta-analysis. A quality appraisal of the studies was performed using the Agency for Healthcare Research and Quality and Newcastle-Ottawa Scales. The pooled results were displayed as odds ratios or standardized mean differences (ORs/SMDs) and 95% confidence intervals (CIs). The article search generated 2273 articles, of which 16 satisfied the inclusion criteria and were merged in the final review. A total of 8556 RA patients were finally included. The pooled prevalence of frailty in the patients with RA was 33.5% (95% CI: 25.2-41.7%), and the pooled prevalence of prefrailty was 39.9% (95% CI: 29.4-50.3%). Subgroup analyses showed that frailty was more prevalent in females (24.7%) than in males (19.1%). The prevalence of prefrailty in females was similar to that in males among the RA patients. Frailty in RA was associated with the female sex (OR: 1.47, 95% CI: 1.04-2.07) and disease activity (OR: 1.47, 95% CI: 1.03-2.09). Frailty is prevalent in RA patients. Female gender and disease activity are associated with the prevalence of frailty in RA patients.

Effect of Janus kinase inhibitors on T cell responses to herpes zoster in rheumatoid arthritis patients.

The incidence of herpes zoster (HZ) in rheumatoid arthritis (RA) patients is greater than that in healthy controls (HC), particularly in RA patients treated with Janus kinase inhibitors (JAKi). Here, we examined the effect of JAKi on CD4+/CD8+ T cells, cytokine production, and regulation of transcriptional factors in RA patients and HC. Peripheral blood mononuclear cells (PBMCs) obtained from RA patients (n=14) and HCs (n=7) were stimulated with varicella zoster virus lysates and exposed to three JAKi inhibitors (ruxolitinib [JAK1/2 inhibitor]; AG490 [JAK2 inhibitor]; and WHI-P154 [JAK3 inhibitor]) in the presence/absence of methotrexate. The CD4+ and CD8+ T cell populations were measured by flow cytometry. Cytokine levels in culture medium were measured by ELISA. Transcription factor expression was examined by RT-qPCR. There was a reduction in the CD4+IFN-γ+, CD4+CD69+IFN-γ+, CD8+IFN-γ+, and CD8+CD69+IFN-γ+ populations, and an increase in the CD4+CD25highFoxp3+ cell population, in PBMCs from RA patients and HCs after exposure to the three JAKi. ELISA revealed a reduction in IFN-γ and granzyme B levels in the presence of JAKi. JAKi reduced expression of mRNA encoding STAT1 and T-bet, but increased that of mRNA encoding STAT5 and Foxp3. Methotrexate plus the highest dose of each JAKi did not affect the Th1, cytotoxic T cell, or Treg populations, the levels of IFN-γ and granzyme B, or expression of transcription factors, significantly. JAKi reduce the Th1/cytotoxic T cell population and increase the Treg population in both RA patients and HC patients.

False-positive detection of IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies in patients with rheumatoid arthritis: Possible effects of IgM or IgG rheumatoid factors on immunochromatographic assay results.

Objectives:The severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019. A serological test is conducted to determine prior infection by severe acute respiratory syndrome coronavirus 2. We investigated whether the results of anti-severe acute respiratory syndrome coronavirus 2 antibody tests are modified in patients with rheumatoid arthritis.Methods:Patients in Japan with rheumatoid arthritis were recruited at Sagamihara Hospital from July 2014 to October 2015 (n = 38; 2014 cohort) and at Tokyo Hospital from June to October 2020 (n = 93; 2020 cohort). Anti-severe acute respiratory syndrome coronavirus 2 antibodies were measured by electrochemiluminescence immunoassay or immunochromatographic assay.Results:Anti-severe acute respiratory syndrome coronavirus 2 antibodies were not detected in any of the samples from rheumatoid arthritis patients tested by electrochemiluminescence immunoassay. Anti-severe acute respiratory syndrome coronavirus 2 antibodies were detected by immunochromatographic assay in the 3 (7.9%) serum samples in the 2014 cohort and 15 (16.1%) serum samples in the 2020 cohort. The IgM rheumatoid factor levels were increased in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (mean ± standard deviation (IU/ml), 1223.0 ± 1308.7 versus 503.6 ± 1947.2; P = 0.0101). The levels of IgG rheumatoid factor were also upregulated in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (4.0 ± 0.7 versus 2.4 ± 0.9; P = 0.0013).Conclusion:The results of IgM anti-severe acute respiratory syndrome coronavirus 2 antibody testing by immunochromatographic assay are modified by IgM or IgG rheumatoid factors in rheumatoid arthritis patients.

Regulatory and other rheumatoid factors in rheumatoid arthritis patients with active disease or in remission.

BackgroundPreviously, we identified a regulatory rheumatoid factor (regRF), the production of which provides rats with resistance to collagen‐induced arthritis (CIA). Immunization with conformers of IgG Fc fragments carrying epitopes specific to regRF reduces symptoms of CIA. The aim of this study was to determine whether there is a link between regRF levels and rheumatoid arthritis (RA) activity in humans in order to assess the potential of regRF as a therapeutic biotarget in RA. The variability of rheumatoid factor (RF) specificities present in the blood of RA patients was also studied.MethodsThe regRF were studied in RA patients with active disease and in remission. Variability in the specificities of RF associated with RA was studied by concurrent inhibition of RF latex fixation by variants of modified IgG.ResultsPatients in remission had regRF levels higher than in healthy subjects. The regRF in remission was characterized by tight binding to its antigen, as in healthy subjects. The regRF levels in patients with active RA varied dramatically, and regRF binding to its antigen was weak. The exacerbation of Still's disease coincided with low regRF levels and affinity, while an improvement in patient condition was associated with an increase in regRF levels and affinity. The RF specific to RA, which was detected by the RF latex‐fixation method, was a nonhomogeneous population of antibodies that included RF to lyophilized IgG, to IgG immobilized on polystyrene, and to rabbit IgG.ConclusionStimulating regRF production might enable improved RA therapy.

Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region.

BackgroundClinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region.MethodsRA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission.FindingsA total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission.InterpretationRemission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.

Evaluation of C-Reactive Protein and Associated Factors Among Patients Suffering from Rheumatoid Arthritis at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder, which is associated with increased pro-inflammatory mediators to induce an elevation in acute-phase response, migration of immune cells and swelling of synovial joints. Evaluation of the level of C-reactive protein and associated risk factors in RA patients was the main aim of this study. Identifying the association between disease activity of RA (hsCRP) and socio-demographic characteristics was another aim of the study.MethodsInstitution-based cross-sectional study was conducted at the Rheumatology Clinic of Tikur Anbessa Specialized Hospital. In this study, the level of hsCRP was measured in both case and control groups. Simple descriptive statistics, multivariate analysis, independent sample t-test were utilized for statistical analysis. The strength of association between different risk factors and hsCRP was measured using odds ratio and 95% confidence interval. P-value < 0.05 was considered as statistically significant.ResultThe result of this study showed that the hsCRP level was significantly higher among RA patients as compared to the control groups (P-value = 0.004). There was an association between smoking and high disease activity status (AOR= 20.03, p= 0.40). Low economic status had a statistically significant association with high hsCRP level (AOR = 12.79, p=0.00). In this study, 42 RA patients had >3mg/l hsCRP level with different occupational exposures. On the other hand, 31 RA patients had <3mg/l hsCRP level among different exposures. Although there was no statistically significant association, the association between associated risk factors (oil consumption, physical exercise, educational status) and disease activity was computed in this study.ConclusionThe inflammatory marker, hsCRP was significantly higher among patients as compared to controls. The higher hsCRP showed a high grade of systemic inflammation in RA patients. C-reactive protein was elevated in rheumatoid factor positive patients and patients with high BMI value. Additionally, the result of our study showed that different socio-economic factors had an association with disease activity of RA.