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Introduction: The safety and efficacy of upadacitinib 15 mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study. Methods: Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24 weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. The safety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216. Results: The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n = 277/309) that initially received ABA. Of patients on UPA15 in the LTE (n = 547), 28.3% (n = 155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in the American College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI), patient's assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n = 263/303, 86.8%; ABA to UPA15: n = 273/309, 88.3%) showed similar responses to the total population. Conclusions: The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343. Plain Language Summary: A long-term study looked at a drug named upadacitinib to treat people with rheumatoid arthritis (RA), a disease that causes joint pain and damage. The study included patients whose RA was not improved by other injectable medicines. The study compared upadacitinib with another drug called abatacept. After 24 weeks, patients who were taking abatacept switched to upadacitinib, and patients taking upadacitinib continued on upadacitinib treatment for over 4 years. The researchers looked at how well the treatments worked over the long-term and if there were any side effects. The side effects with upadacitinib treatment in this long-term study were similar to side effects reported in previous studies with upadacitinib. The researchers also found that upadacitinib helped to lessen the symptoms of RA over time and helped patients complete their daily activities and reduced their pain and tiredness. This was true for patients who switched from abatacept to upadacitinib after 24 weeks and for patients who took upadacitinib from the start of the study. Patients who had not responded to other medicines also had similar improvements with upadacitinib. In conclusion, upadacitinib can help people with RA over the long term and no new safety risks were found. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Methods: Summary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we appliedmultiple robust analytical methods, with the inverse varianceweighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions. Results: A potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 - 1.49, P < 0.001), which was further confirmed by metaanalysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 - 1.50, P < 0.001), and this was also confirmed by metaanalysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them. Conclusion: Our study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis. Methods: We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods. Results: GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA. Conclusion: Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) remains a challenging chronic autoimmune disorder characterized by persistent joint inflammation and damage. While modern regenerative strategies, encompassing cell/stem cell-based therapies, gene therapy, and tissue engineering, have advanced tissue repair efforts, a definitive cure for RA remains elusive. Consequently, there is growing interest in developing targeted therapies that directly address the underlying mechanisms driving RA pathogenesis, such as extracellular vesicles (EVs). These small membrane-bound particles can modulate immune responses within the inflammatory microenvironment of damaged cartilage. To launch the clinical potential of EVs, they can be isolated from various cell types through several techniques. EVs can carry various bioactive molecules and anti-inflammatory or pro-regenerative drugs, deliver them directly to the affected joints, and affect the behavior of injured cells, making them a compelling choice for targeted therapy and drug delivery in RA patients. However, there are still several challenges and limitations associated with EV-based therapy, including the absence of standardized protocols for EV isolation, characterization, and delivery. This review provides a comprehensive overview of the cellular sources of EVs in RA and delves into their therapeutic potential and the hurdles they must overcome. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, advanced therapy medicinal products (ATMPs) have revolutionised medicine with the promise of new treatments for previously incurable diseases. Chimeric antigen receptor (CAR T) cell therapies, in particular, have emerged as a highly active area of research and entrepreneurship. CAR T-cells are generated by introducing into T-cells a chimeric receptor (CAR). The CAR confers the T-cells the capacity to recognise a molecule expressed by the tumour. There are at least 10 different CAR T-cells with approval by different regulatory agencies around the globe. Several clinical trials have been performed in patients with solid tumours, as well as in patients with autoimmune conditions. There are several studies showing the potential benefit of CAR T-cells for other non-malignant diseases such as asthma and even fungal infections. We offer a brief summary of some of the most relevant aspects of the use of CAR T-cells for some of these conditions. The use of chimeric antigen receptors (CAR T-cells) for the treatment of patients with malignant haematological diseases has become a well-established application for conditions such as refractory or relapsed B-cell acute lymphoblastic leukaemia (B-ALL), B-cell lymphomas (BCL), and multiple myeloma (MM). Nearly 35,000 patients have received autologous CAR T-cells for the treatment of these conditions only in the USA. Since their approval by the Food and Drug Administration (FDA) in 2017, over 1200 clinical trials have been initiated globally and there are at least 10 different CAR T-cells with approval by different regulatory agencies around the globe. In the USA, the FDA has approved six commercial CAR T-cells that are widely distributed worldwide. At the time of writing, several clinical trials have been performed in patients with solid tumours such as glioblastoma, renal and pancreatic cancer, as well as in patients with autoimmune conditions such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SS). There are also several studies showing the potential benefit of CAR T-cells for other non-malignant diseases such as asthma and even fungal infections. In this review, without pretending to cover all current areas of treatments with CAR T-cells, we offer a brief summary of some of the most relevant aspects of the use of CAR T-cells for some of these conditions. [ABSTRACT FROM AUTHOR]

The most prevalent inflammatory arthritis and a leading contributor to disability is rheumatoid arthritis (RA). Although it may not have arrived in Europe until the 17th century, it was present in early Native American communities several thousand years ago. Exosomes released by mesenchymal stem cells (MSCs) are highly immunomodulatory due to the origin of the cell. As a cell-free therapy, MSCs-exosomes are less toxic and elicit a weakened immune response than cell-based therapies. Exosomal noncoding RNAs (ncRNAs) are closely associated with a number of biological and functional facets of human health, especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Various exo-miRNAs and lncRNAs such as HAND2-AS1, miR-150-5p, miRNA-124a, and miR-320a lodged with MSC could be appropriate therapeutic ways for RA treatment. These MSC-derived exosomes affect RA disorders via different molecular pathways such as NFK-β, MAPK, and Wnt. The purpose of this review is to review the research that has been conducted since 2020 so far in the field of RA disease treatment with MSC-loaded exo-miRNAs and exo-lncRNAs. [ABSTRACT FROM AUTHOR]

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn's disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer's disease (AD) and Parkinson's disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis can be classified according to ACPA and RF status. ACPA status may be associated with other pathophysiological differences, e.g., the cytokines driving inflammation. Obesity influences the course of RA, likely involving leptin; the exact mechanisms are not completely understood. This study investigates BMI influence on RA cytokine profiles and the possibility of predicting ACPA status and disease activity measured by Power-Doppler sonography (PDS). Methods: Patients were examined using a multi-biomarker disease assay and PDS examination of wrists and MCP and PIP joints and stratified according to ACPA status and BMI, using prediction precision to determine BMI cutoff. Analysis was performed using elastic net regularization of logistic and multiple regression. We then attempted to predict ACPA status/PDS activity based on a bootstrap approach. Results: A total of 120 measurements from 95 patients were performed. ACPA status prediction peaked at BMI 26 kg/m2, with AUC 0.82. PDS activity prediction had a mean average error of < 1.6 PDS points for all groups. In obese patients, cytokine profiles appear to align in ACPA-positive and -negative patients, with leptin playing a greater role in predicting PDS activity, but with some remaining differences. Conclusion: When stratified according to BMI, cytokine patterns can predict ACPA status and PDS activity in RA with a high degree of precision. This indicates that studies into the pathophysiology of RA should take BMI into account, to differentiate between disease- and obesity-associated phenomena. The underlying pathological processes of ACPA-negative and -positive RA appear different. Multi-cytokine evaluations may provide a deeper understanding of disease processes. Key Points • A multi-cytokine approach combined with ultrasonography and modern mathematical methods can contribute to a deeper understanding of the relationship between systemic and joint inflammation. • BMI influences cytokine profiles in rheumatoid arthritis and appears to "override" disease-specific processes. • Using cytokines only, and adjusting for BMI, it is possible to predict the ACPA status and joint inflammation with considerable precision. [ABSTRACT FROM AUTHOR]

Purpose: This aimed to identify the factors associated with severe/critical coronavirus disease 2019 (COVID-19) infection in rheumatoid arthritis (RA) patients. Methods: Two-hundred RA patients diagnosed according to the American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria with proven COVID-19 infection were recruited and categorized according to the world health organization (WHO) COVID-19 severity grading into 2 groups: patients with mild/moderate COVID-19 (n = 164) and patients with severe/critical COVID-19 (n = 36). Comparison between both groups was done to identify the risk factors associated with severe/critical infection. Incidence of RA disease activity flare defined as increase in clinical disease activity index (CDAI) more than 10 points following infection was calculated. Results: Multivariate analysis identified history of previous serious infection, age > 60 years, and diabetes as factors positively associated, whereas COVID-19 vaccination was negatively associated with severe/critical infection. Following COVID-19 infection, the number of patients with severe/critical COVID-19 who had high RA disease activity and the incidence of flares was significantly higher in comparison to patients with mild/moderate COVID-19 (P < 0.001 and 0.003; respectively). Conclusion: Age > 60 years, diabetes, and history of previous serious infections are risk factors for severe/critical COVID-19, while vaccination has a protective role in RA patients. Infection particularly when severe is associated with risk of disease flare. [ABSTRACT FROM AUTHOR]

Abstract Background Osteoarthritis (OA) and rheumatoid arthritis (RA) are often difficult to distinguish in the early stage of the disease. The purpose of this study was to explore the similarities and differences between the two diseases through Mendelian randomization (MR) and transcriptome analysis. Methods We first performed a correlation analysis of phenotypic data from genome-wide association studies (GWAS) of OA and RA. Then, we performed functional and pathway enrichment of differentially expressed genes in OA, RA, and normal patients. The infiltration of immune cells in arthritis was analyzed according to gene expression. Finally, MR analysis was performed with inflammatory cytokines and immune cells as exposures and arthritis as the outcome. The same and different key cytokines and immune cells were obtained by the two analysis methods. Results GWAS indicated that there was a genetic correlation between OA and RA. The common function of OA and RA is enriched in their response to cytokines, while the difference is enriched in lymphocyte activation. T cells are the main immune cells that differentiate between OA and RA. MR analysis further revealed that OA is associated with more protective cytokines, and most of the cytokines in RA are pathogenic. In addition, CCR7 on naive CD4 + T cell was positively correlated with OA. SSC-A on CD4 + T cell was negatively correlated with RA, while HLA DR on CD33- HLA DR + was positively correlated with RA. Conclusion Our study demonstrated the similarities and differences of immune inflammation between OA and RA, allowing us to better understand these two diseases.

Abstract Rheumatoid arthritis (RA) remains a challenging chronic autoimmune disorder characterized by persistent joint inflammation and damage. While modern regenerative strategies, encompassing cell/stem cell-based therapies, gene therapy, and tissue engineering, have advanced tissue repair efforts, a definitive cure for RA remains elusive. Consequently, there is growing interest in developing targeted therapies that directly address the underlying mechanisms driving RA pathogenesis, such as extracellular vesicles (EVs). These small membrane-bound particles can modulate immune responses within the inflammatory microenvironment of damaged cartilage. To launch the clinical potential of EVs, they can be isolated from various cell types through several techniques. EVs can carry various bioactive molecules and anti-inflammatory or pro-regenerative drugs, deliver them directly to the affected joints, and affect the behavior of injured cells, making them a compelling choice for targeted therapy and drug delivery in RA patients. However, there are still several challenges and limitations associated with EV-based therapy, including the absence of standardized protocols for EV isolation, characterization, and delivery. This review provides a comprehensive overview of the cellular sources of EVs in RA and delves into their therapeutic potential and the hurdles they must overcome.

• Identification of protein biomarkers for predicting Tocilizumab response in Rheumatoid arthritis. • High-precision proteomics approach using Data-independent acquisition mass spectrometry in RA patient serum. • Developed a robust multi-biomarker panel with 86 % discriminative power and 0.84 AUC. • Potential diagnostic tool for TCZ non-responder prediction in RA patients. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation in the synovial lining of the joints. Key inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, and others play a critical role in the activation of local synovial leukocytes and the induction of chronic inflammation. Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, has demonstrated significant clinical efficacy in treating RA patients. However, similar to other inflammatory cytokine blockers, such as TNF-alpha inhibitors, Interleukin-1 inhibitors, or CD20 inhibitors, some patients do not respond to treatment. To address this challenge, our study employed a high-precision proteomics approach to identify protein biomarkers capable of predicting clinical responses to Tocilizumab in RA patients. Through the use of data-independent acquisition (DIA) mass spectrometry, we analyzed serum samples from both TCZ responders and non-responders to discover potential biomarker candidates. These candidates were subsequently validated using individual serum samples from two independent cohorts: a training set (N = 70) and a test set (N = 18), allowing for the development of a robust multi-biomarker panel. The constructed multi-biomarker panel demonstrated an average discriminative power of 86 % between response and non-response groups, with a high area under the curve (AUC) value of 0.84. Additionally, the panel exhibited 100 % sensitivity and 60 % specificity. Collectively, our multi-biomarker panel holds promise as a diagnostic tool to predict non-responders to TCZ treatment in RA patients. [ABSTRACT FROM AUTHOR]

Abstract Introduction The safety and efficacy of upadacitinib 15 mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study. Methods Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24 weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. The safety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216. Results The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n = 277/309) that initially received ABA. Of patients on UPA15 in the LTE (n = 547), 28.3% (n = 155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP])

Abstract Background Vaccines are a crucial component of the global efforts to control the spread of COVID-19. Very little is known about COVID-19 vaccine responses in patients living with autoimmune rheumatic conditions in Africa. We examined the clinical reaction to COVID-19 vaccinations in Ghanaians diagnosed with autoimmune rheumatic disease. Methods This was a hospital-based interventional cohort study of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients recruited via regular face-to-face clinic visits. The systemic lupus erythematosus disease activity index Selena modification (SELENA-SLEDAI) and the disease activity score 28-joint count-erythrocyte sedimentation rate (DAS28-ESR) were used to measure changes in disease activity levels. Results Thirty-eight (38) patients of which 21 (55.3%) were diagnosed with SLE and 17 (44.7%) with RA contributed data for analyses. Most (89.5%) of the patients were females, with a mean age of 37.4 years. The SLE patients experienced a notable increase in severe flares during weeks three and six, as well as the third and sixth months, followed by subsequent decreases in the twelfth month, while remission levels increased throughout the same period. Among RA patients, high disease activity decreased during weeks three and six, as well as the third, sixth, and twelfth months, with remission levels increasing during the same time. A low dose (≥ 50

This article explores the use of reverse V-shaped osteotomy as a treatment for ankylosing rocker-bottom foot deformity in patients with rheumatoid arthritis (RA). The study examined three cases where patients with RA and foot deformities underwent the procedure, which successfully corrected the deformities and improved their clinical scores. The authors suggest that reverse V-shaped osteotomy could be a valuable and definitive procedure for this type of foot deformity in RA patients. The study acknowledges the need for additional research and highlights some limitations. [Extracted from the article]

Angiogenesis is critical for rheumatoid arthritis (RA) progression. The effects of tofacitinib, a JAK-STAT inhibitor used for RA treatment, on angiogenesis in RA are unclear. We, therefore, evaluated the levels of angiogenic factors in two systems of a human co-culture of fibroblast (HT1080) and monocytic (U937) cell lines treated with tofacitinib and in serum samples from RA patients before and after six months of tofacitinib treatment. Tofacitinib reduced CD147 levels, matrix metalloproteinase-9 (MMP-9) activity, and angiogenic potential but increased endostatin levels and secreted proteasome 20S activity. In vitro, tofacitinib did not change CD147 mRNA but increased miR-146a-5p expression and reduced STAT3 phosphorylation. We recently showed that CD147 regulates the ability of MMP-9 and secreted proteasome 20S to cleave collagen XVIIIA into endostatin. We show here that tofacitinib-enhanced endostatin levels are mediated by CD147, as CD147-siRNA or an anti-CD147 antibody blocked proteasome 20S activity. The correlation between CD147 and different disease severity scores supported this role. Lastly, tofacitinib reduced endostatin' s degradation by inhibiting cathepsin S activity and recombinant cathepsin S reversed this in both systems. Thus, tofacitinib inhibits angiogenesis by reducing pro-angiogenic factors and enhancing the anti-angiogenic factor endostatin in a dual effect mediated partly through CD147 and partly through cathepsin S. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and inflammatory cellular infiltration. Functional cells in the RA microenvironment (RAM) are composed of activated immune cells and effector cells. Activated immune cells, including macrophages, neutrophils, and T cells, can induce RA. Effector cells, including synoviocytes, osteoclasts, and chondrocytes, receiving inflammatory stimuli, exacerbate RA. These functional cells, often associated with the upregulation of surface-specific receptor proteins and significant homing effects, can secrete pro-inflammatory factors and interfere with each other, thereby jointly promoting the progression of RA. Recently, some nanomedicines have alleviated RA by targeting and modulating functional cells with ligand modifications, while other nanoparticles whose surfaces are camouflaged by membranes or extracellular vesicles (EVs) of these functional cells target and attack the lesion site for RA treatment. When ligand-modified nanomaterials target specific functional cells to treat RA, the functional cells are subjected to attack, much like the intended targets. When functional cell membranes or EVs are modified onto nanomaterials to deliver drugs for RA treatment, functional cells become the attackers, similar to arrows. This study summarized how diversified functional cells serve as targets or arrows by engineered nanoparticles to treat RA. Moreover, the key challenges in preparing nanomaterials and their stability, long-term efficacy, safety, and future clinical patient compliance have been discussed here. [Display omitted] • This article summarizes the role of different functional cells in rheumatoid arthritis. • In this paper, we reviewed the overexpressed protein receptors on the surfaces of different rheumatoid arthritis-related cells. • This paper summarizes the mechanism of emerging nanomedicines targeting rheumatoid arthritis-related cells. • Authors raise an innovative idea that functional cells can serve as both targets and arrows in the process of rheumatoid arthritis treatment by engineered nanoparticles. [ABSTRACT FROM AUTHOR]

ANCA-associated vasculitis (AAV) can affect multiple organs with severe life-threatening manifestations. Disease monitoring is difficult due to a lack of defined biomarkers. We aimed to assess the diagnostic role of serum interleukin-6 and vascular ultrasonography in AAV and subclinical atherosclerosis. The study included 20 AAV patients and two control groups of 34 patients with rheumatoid arthritis (RA) and 35 healthy controls. The levels of Il-6, carotid intima-media thickness test (CIMT), atherosclerotic plaque, and degree of stenosis were investigated. A GRACE-risk score was calculated for AAV and RA patients. The AAV patients had elevated levels of IL-6 (115 ± 23.96) compared to the RA patients (91.25 ± 42.63) and the healthy controls (15.65 ± 3.30), p < 0.001. IL-6 showed a diagnostic accuracy of 73% in distinguishing AAV from RA patients (AUC = 0.730; 95% CI 0.591 to 0834). In the AAV group, CIMT was 1.09, above the upper reference value of 0.90, p < 0.001. The AAV patients had a higher median GRACE risk score, and 60% of them had a high risk of cardiovascular events as compared to 35% of the RA patients. Sonography of extracranial vessels and serum levels of IL-6 can be used in daily clinical practice to diagnose and monitor patients with AAV. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA), a chronic inflammatory disease, carries a significant burden of atherosclerotic cardiovascular diseases (ASCVD). With their heterogeneous composition, high-density lipoprotein (HDL) particles have varied athero-protective properties, and some may even increase ASCVD risk. In this prospective and cross-sectional study, we aimed to examine the relationship between HDL sizes/metabolites and inflammation in RA. Using 1H-NMR-based lipid/metabolomics, differential HDL-related metabolites were identified between RA patients and healthy control (HC) subjects and between RA patients with and without anti-citrullinated peptide antibodies (ACPA). The correlation between the discriminative HDL-related metabolites and C-reactive protein (CRP) was evaluated in RA patients. RA patients demonstrated higher particle number, lipids, cholesterol, cholesterol ester, free cholesterol, and phospholipids in large/very large-sized HDLs. ACPA-positive patients had higher L-HDL-C and L-HDL-CE but lower small-/medium-sized HDL-TG levels than ACPA-negative patients. An inverse correlation was found between CRP levels and small-sized HDLs. Janus kinase inhibitor treatment was associated with increased serum small-sized HDL-related metabolites and decreased CRP levels. We are the first to reveal the significant associations between RA inflammation and HDL sizes/metabolites. A potential link between ACPA positivity and changes in serum levels of HDL-related metabolites was also observed in RA patients.

BackgroundMicronutrients play a crucial role in rheumatoid arthritis (RA). Changes in micronutrient levels in RA patients can lead to the worsening of their condition. Though significant correlations between RA and micronutrients have been found in earlier observational studies, their underlying causal relationship is still unknown. This study aimed to elucidate the causal genetic relationships between 15 micronutrients (copper, zinc, magnesium, vitamins A, C, E, D, B6, B12, folate, carotene, iron, selenium, calcium, potassium) and RA.MethodThe exposure factors and outcome data used in the two-sample Mendelian randomization (MR) were derived from publicly available summary statistics data of European populations. The GWAS data for exposure factors were obtained from the OpenGWAS database. For the outcome data of RA, we utilized data from the FinnGen database. We used the MR principle to remove confounding factors and conducted MR analyses using five methods: inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode, with IVW as the primary method. Then, we identified micronutrients related to RA and performed MR analyses on these elements, including heterogeneity analysis and pleiotropy analysis such as MR-Egger intercept, MR-PRESSO method, and “leave-one-out” analysis. Finally, we conducted multivariable MR analyses and performed sensitivity analyses again.ResultsThe IVW analysis revealed a relationship between vitamin B6 and RA (p: 0.029, OR: 1.766, and 95% CI: 1.062–2.938). Sensitivity analysis confirmed the validity and reliability of this result.ConclusionThis study revealed a causal relationship between vitamin B6 and RA, with vitamin B6 being identified as a risk factor for RA. This finding could contribute to the diagnosis and supplementary treatment of RA patients, providing a reference for subsequent basic research and developing new drugs.

ObjectiveThe risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) remains inadequately defined. Consequently, this study aims to evaluate the predictive value of remnant cholesterol (RC) for assessing CVD risk in RA patients.MethodsPlasma RC levels were measured in 114 RA patients and 41 healthy controls, calculated as total cholesterol minus HDL-C and LDL-C. These levels were further analyzed using 1H-NMR lipid/metabolomics. Meanwhile, the 28-joint Disease Activity Score (DAS28) assessed RA activity.ResultsRC levels were significantly elevated in RA patients (19.0 mg/dl, p

Cellular therapies utilizing regulatory T cells (Tregs) have flourished in the autoimmunity space as a new pillar of medicine. These cells have shown a great promise in the treatment of such devastating conditions as type 1 diabetes mellitus (T1DM), systemic lupus erythematosus (SLE) and graft versus host disease (GVHD). Novel treatment protocols, which utilize Tregs-mediated suppressive mechanisms, are based on the two main strategies: administration of immunomodulatory factors affecting Tregs or adoptive cell transfer (ACT). ACT involves extraction, in vitro expansion and subsequent administration of Tregs that could be either of autologous or allogeneic origin. Rheumatoid arthritis (RA) is another autoimmune candidate where this treatment approach is being considered. RA remains an especially challenging adversary since it is one of the most frequent and debilitating conditions among all autoaggressive disorders. Noteworthy, Tregs circulating in RA patients' blood have been proven defective and unable to suppress inflammation and joint destruction. With this knowledge, adoptive transfer of compromised autologous Tregs in the fledgling clinical trials involving RA patients should be reconsidered. In this article we hypothesize that incorporation of healthy donor allogeneic Tregs may provide more lucid and beneficial results.

Abstract Background The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC—apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). Methods Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. Results The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P

Background Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. Methods A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. Results The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47–2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74–36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85–2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19–1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34–1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204–3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001–1.009, p = 0.014). Conclusions Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention.

ABSTRACTBackground Despite evidence linking viruses and oral microbiome to rheumatoid arthritis (RA), limited whole genome sequencing research has been conducted on the oral virome (a viral component of the microbiome) of untreated RA patients. This pilot research seeks to address this knowledge gap by comparing the oral virome of untreated rheumatoid arthritis patients (RAs) and healthy individuals (HCs).Method Whole genome DNA sequence of saliva samples from 45 participants including 21 RAs and 24 age and gender matched HCs was obtained from the BioProject: PRJEB6997. Metaphlan3 pipeline and LEfSe analysis were used for the viral signature detection. Wilcoxon pairwise test and ROC analysis were used to validate and predict signatures.Results RA exhibits higher alpha diversity compared to HCs. Callitrichine gammaherpesvirus 3, Human gammaherpesvirus 4 (EBV), Murid betaherpesvirus 8, and Suid alphaherpesvirus 1 were enriched in RAs, while Aotine betaherpesvirus 1 from the Cytomegalovirus genus was enriched in HCs. In addition, Saccharomyces cerevisiae killer virus M1 (ScV-M1) was found to be enriched in RAs, whereas bacteriophage Hk97virus (Siphoviridae) and Cd119virus (Myoviridae) were enriched in HCs.Conclusion This study identifies significant DNA oral viral signatures at species level as potential biomarkers for the early detection and diagnosis of rheumatoid arthritis.

Objective: To explore the distribution rules of traditional Chinese medicine (TCM) syndromes in patients with rheumatoid arthritis (RA) in the northern Xinjiang region and their inherent relationship with related factors, in order to assistant the clinical treatment of RA. Methods: A total of 217 patients with RA in the northern Xinjiang region were collected. The TCM syndrome types, tongue coating, pulse condition, symptoms, disease duration, disease activity score 28 (DAS28), and indicators such as IL-1β and BMP6 detected by ELISA were statistically analyzed. Results: There are more female RA patients than male RA patients. The proportions of TCM syndrome types were as follows: cold-damp obstruction syndrome > liver-kidney deficiency syndrome > phlegm-stasis obstruction syndrome > damp-heat obstruction syndrome > rheumatic obstruction syndrome > qi-blood deficiency syndrome. There was no statistical difference in the distribution of gender and age among different TCM syndrome types in RA patients (P>0.05) . The main characteristics of TCM syndromes in this region were morning stiffness of joints, fixed joint pain, joint pain relieved by pressing, increased pain in cold weather, difficulty in joint flexion and extension, soreness and weakness of waist and knees, lighter symptoms during the day and heavier at night, worsened symptoms on rainy days, and heavy limbs. There were statistical differences in disease duration, DAS28, C-reactive protein, and BMP6 among different TCM syndrome types (P<0.05) and no statistical differences in IL-6, IL-1β, RF and CCP (P> 0.05) . Compared with other syndrome types, the C-reactive protein of wind-dampness impediment was higher than that of deficiency of liver and kidney, the DAS28 disease activity level of cold-dampness impediment was higher than that of deficiency of liver and kidney, the BMP6 level of damp-heat impediment was higher than that of wind-dampness impediment, cold-dampness impediment, and the BMP6 level of phlegm-stasis impediment was higher than that of wind-dampness impediment. Conclusion: The characteristics of traditional Chinese medicine syndroms of RA patients in northern Xinjiang are mainly "cold", "dampness" and "deficiency", and the syndrome type is the most common cold-dampness obstruction syndrome, and the disease activity is high. The abnormal manifestations of bone and joint in damp-heat obstruction syndrome and phlegm-stasis obstruction syndrome are more prominent, and the level of BMP6 is relatively high. Age and gender have an influence on the onset of RA, and the duration of disease has an influence on the distribution of TCM syndromes of RA. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are serological markers used for diagnosing rheumatoid arthritis (RA), an autoimmune disease characterized by inflammatory joint damage. However, there is a subset of RA patients who test negative for both RF and ACPA, known as seronegative rheumatoid arthritis (SNRA). Material and methods: The levels of serum markers were examined in both clinical samples and a rat model of type II collagen-induced RA (CIA). The effect of interleukin 9 (IL-9) on RA was investigated using recombinant rat IL-9 (rrIL-9), anti-rat IL-9 neutralizing monoclonal antibody (mAb), and control IgG antibody in the CIA rat. The severity of arthritis was assessed. Treg and Th17 cells, M1 and M2 macrophages, and inflammatory cytokine levels were analyzed. Results: We observed higher levels of IL-9 in clinical samples from SNRA patients compared to the normal group. Rat models of CIA exhibit increased arthritis scores, weight loss, paw swelling, and severe joint damage. IL-9 was the most sensitive serum marker for the diagnosis of RA in serum assays of CIA rats. IL-9 increased arthritis scores and cartilage damage, whereas treatment with IL-9 inhibitors produced the opposite effect. IL-9 inhibitors promoted Treg/Th17 homeostasis, decreased M1 macrophages, increased M2 macrophages, and decreased levels of inflammatory cytokines in joint tissues. Conclusions: These results suggest that IL-9 has potential as a diagnostic marker for SNRA. Inhibition of IL-9 could reduce the severity of arthritis in CIA rats by ameliorating inflammation and modulating the Treg/Th17 immune balance, M2 and M1 macrophage activation. [ABSTRACT FROM AUTHOR]

Background: Oral health-related quality of life (OHRQoL) has been investigated as a component of health-related quality of life (HRQoL) in recent years. However, there is a lack of local data using OHRQoL questionnaires to assess life quality in individuals rheumatoid arthritis (RA) at the present time. Objectives: to assess the OHRQoL of RA patients and explore any potential effects of various clinical indicators. Methods: A cross-sectional study compared 100 RA patients and 100 control individuals to assess and compare their OHRQoL. The study examined the Oral Health Impact Profile (OHIP-14) as one of the oral health factors under investigation, examining the association between the disease activity score of RA (CDAI and DAS28) and the OHIP. Results: Patients with RA had a median OHIP-14 of 14 (4–24.5), while controls had a median of 6 (2–18), yielding a significant difference (p = 0.005). A significant positive yet weak correlation was observed between OHIP-14 and CDAI (r = 0.26, p = 0.009). A weak positive correlation was seen between OHIP-14 and DAS28, although the correlation did not attain statistical significance (r = 0.15, p = 0.125). Conclusions: Patients with RA reported a more unfavorable evaluation of their OHRQoL compared to those without RA. [ABSTRACT FROM AUTHOR]

Rheumatoid Arthritis (RA) is a systemic inflammatory disorder that commonly presents with polyarthritis but can have multisystemic involvement and complications, leading to increased morbidity and mortality. The diagnosis of RA continues to be challenging due to its varied clinical presentations. In this review article, we aim to determine the potential of PET/CT to assist in the diagnosis of RA and its complications, evaluate the therapeutic response to treatment, and predict RA remission. PET/CT has increasingly been used in the last decade to diagnose, monitor treatment response, predict remissions, and diagnose subclinical complications in RA. PET imaging with [18F]-fluorodeoxyglucose ([18F]-FDG) is the most commonly applied radiotracer in RA, but other tracers are also being studied. PET/CT with [18F]-FDG, [18F]-NaF, and other tracers might lead to early identification of RA and timely evidence-based clinical management, decreasing morbidity and mortality. Although PET/CT has been evolving as a promising tool for evaluating and managing RA, more evidence is required before incorporating PET/CT in the standard clinical management of RA. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is an underdiagnosed disorder that affects an estimated 6-10% of women of reproductive age. Endometriosis has been reported in epidemiological studies to be associated with autoimmune diseases. However, the relationship remains controversial. Methods: A meta-analysis of observational studies was undertaken to evaluate the risk of autoimmune diseases in patients with endometriosis. The relevant studies were retrieved via the databases Medline, Embase and Web of Science until July 20, 2023. Mendelian randomization (MR) was subsequently utilized to scrutinize the causal influence of genetic predisposition toward endometriosis on three autoimmune diseases. Results: The meta-analysis findings revealed a relationship between endometriosis and the onset of SLE (cohort studies: RR = 1.77, 95% confidence interval (CI): 1.47–2.13, I2 = 0%; Case-control and cross-sectional studies: OR = 5.23, 95% CI: 0.74–36.98, I2 = 98%), RA (cohort studies: RR = 2.18, 95% CI: 1.85–2.55, I2 = 92%; Case-control and cross-sectional studies: OR = 1.40, 95% CI: 1.19–1.64, I2 = 0%) and SS (cohort studies: RR = 1.49, 95% CI: 1.34–1.66, I2 = 0%). Similarly, in our MR study, the results of the inverse-variance-weighted (IVW) model suggested that genetic predisposition to endometriosis was causally associated with an increased risk for SLE (OR = 1.915, 95% CI: 1.204–3.045, p = 0.006) and RA (OR = 1.005, 95% CI: 1.001–1.009, p = 0.014). Conclusions: Both our meta-analysis and MR study indicate that endometriosis increases the risk of autoimmune diseases. These findings not only broaden our understanding of the genetic mechanisms underlying the comorbidity of endometriosis and autoimmune diseases, but also offer a new strategy for autoimmune disease prevention. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease featuring an abnormal immune microenvironment and resultant accumulation of hydrogen ions (H+) produced by activated osteoclasts (OCs). Currently, clinic RA therapy can hardly achieve sustained or efficient therapeutic outcomes due to the failures in generating sufficient immune modulation and manipulating the accumulation of H+ that deteriorates bone damage. Herein, a highly effective immune modulatory nanocatalytic platform, nanoceria‐loaded magnesium aluminum layered double hydroxide (LDH‐CeO2), is proposed for enhanced immune modulation based on acid neutralization and metal ion inherent bioactivity. Specifically, the mild alkaline LDH initiates significant M2 repolarization of macrophages triggered by the elevated antioxidation effect of CeO2 via neutralizing excessive H+ in RA microenvironment, thus resulting in the efficient recruitment of regulatory T cell (Treg) and suppressions on T helper 17 cell (Th 17) and plasma cells. Moreover, the osteogenic activity is stimulated by the Mg ion released from LDH, thereby promoting the damaged bone healing. The encouraging therapeutic outcomes in adjuvant‐induced RA model mice demonstrate the high feasibility of such a therapeutic concept, which provides a novel and efficient RA therapeutic modality by the immune modulatory and bone‐repairing effects of inorganic nanocatalytic material. [ABSTRACT FROM AUTHOR]

Introduction: This article aims to describe malignancies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or non-radiographic axial spondyloarthritis (nr-axSpA) treated with upadacitinib (UPA) or active comparators. Methods: This integrated safety analysis includes data from 11 phase 3 UPA trials across RA (6 trials), PsA (2 trials), AS (2 trials; one phase 2b/3), and nr-axSpA (1 trial). Treatment-emergent adverse events (TEAEs) were summarized for RA (pooled UPA 15 mg [UPA15], pooled UPA 30 mg [UPA30], adalimumab 40 mg [ADA], methotrexate monotherapy [MTX]), PsA (pooled UPA15, pooled UPA30, ADA), AS (pooled UPA15), and nr-axSpA (UPA15). TEAEs were reported as exposure-adjusted event rates (events/100 patient-years). Results: Median treatment duration ranged from 1.0 to 4.0 years (with a maximum of 6.6 years in RA). Across treatments and indications, rates of malignancy excluding nonmelanoma skin cancer (NMSC) ranged from 0.2 to 1.1, while NMSC ranged from 0.0 to 1.4. In RA, rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX (breast and lung cancer were the most common). In RA and PsA, Kaplan–Meier analyses revealed no differences in event onset of malignancy excluding NMSC with UPA15 versus UPA30 over time. In RA, NMSC rates were higher with UPA30 than UPA15; both UPA15 and UPA30 were higher than ADA and MTX. In PsA, rates of malignancy excluding NMSC and NMSC were generally similar between UPA15, UPA30, and ADA. In AS and nr-axSpA, malignancies were reported infrequently. Few events of lymphoma were reported across the clinical programs. Conclusion: Rates of malignancy excluding NMSC were generally similar between UPA15, UPA30, ADA, and MTX and were consistent across RA, PsA, AS, and nr-axSpA. A dose-dependent increased rate of NMSC was observed with UPA in RA. Trial Registration: ClinicaTrials.gov identifier: NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847, NCT03086343, NCT03104400, NCT03104374, NCT03178487, and NCT04169373. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) can independently increase the risk of stroke, affecting both young and adult RA patients. Recent attention has been drawn to the association between stroke and RA, supported by mounting evidence. Given that stroke is a significant and an urgent public health concern, this review aims to highlight the relationship between stroke and RA, covering mechanisms, underlying risk factors, early detection tools, and treatment implications. By uncovering the connection that links RA to stroke, we can pave the way for targeted healthcare practices and the development of preventive strategies for individuals with RA. Therefore, further research is imperative to deepen our understanding of this association and, ideally, guide treatment decisions for individuals at risk of both RA and stroke. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects 1% of the world's population. It causes chronic inflammation of synovial tissue, leading to joint destruction, poor quality of life, and disability. Cathepsin G (CTSG), which acts as a proteolytic enzyme, can be a factor in RA. These proteases belong to the serine protease family and have a role in autoimmune disorders. They can cause bone and cartilage destruction and an immune response in cases of inflammatory arthritis. The objective of this study is to determine if CTSG could serve as a potential biomarker for the diagnosis and evaluation of the activity of RA. Methods: The study involved 132 patients with inflammatory arthritis, and their serum levels of CTSG and anti-citrullinated peptide antibody (ACPA) were measured using ELISA. Other routine biomarkers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF), were also measured. Results: The mean of CTSG was significantly lower in RA patients (110.53 pg/ml ± 49.959) than in those with other types of inflammatory arthritis (132.65 pg/ml ± 30.199). According to DAS-28 ESR and DAS-28 CRP, the study found no significant difference in CTSG levels across the four disease activity groups (P = 0.585, P = 0.823, respectively). Additionally, CTSG had a significant negative correlation with diabetes mellitus and treatment intake in newly diagnosed RA (P = 0.009, P = 0.041, respectively). This study is the first to evaluate CTSG as an RA diagnostic tool, showing a sensitivity of 70.1% and a specificity of 60.0% at a cut-off value of ≤133.33 pg/ml. Conclusions: The study results suggest that CTSG has potential as a diagnostic biomarker for RA when used alongside other clinical and laboratory criteria. However, it should not be solely relied upon for evaluating RA activity.

Background: It is well known that ursodeoxycholic acid (UDCA) has notable impacts on the liver, However, tiny amount of knowledge available on how it affects autoimmune illness. This research was done to see an advantage that might exist of using UDCA in Rheumatoid arthritis (RA). Methods: In order to accomplish this objective, adult either sex rats were divided into 4 groups: Normal control (sodium bicarbonate 5% p.o. for 21 days),CFA (0.1 ml CFA footpad intradermal injection),FCA+ Diclofenac (5 mg/kg p.o for 21 days),FCA+ UDCA (100 mg/kg p.o. for 21 days). Results: UDCA (100 mg/kg p.o.) show significantly a rise in Body Mass also significantly reduce in Arthritic Oedema score in comparison with induction group . RBC, WBC, and ESR were Hematological UDCA therapy of animals Evaluation findings RBC increased noticeably and WBC ,ESR levels drop noticeably. a considerable drop in TNFα and RF biochemical parameters evaluated in UDCA treatment group. Keywords: rheumatoid arthritis (RA); ursodeoxycholic acid (UDCA) and Complete Freund adjuvant (CFA)

Abstract Background This study aimed to assess the association between social factors, demographic parameters, and disease activity among rheumatoid arthritis (RA) patients. Methods The University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry was used for this study and included patients meeting 1987 ACR criteria for RA enrolled between 2010–2015. The registry collected clinical and laboratory data at each visit, permitting the calculation of disease activity measures that included Disease Activity 28-C Reactive Protein (DAS28-CRP). The current study was conducted as a cross-sectional study in which baseline data were used to construct multiple logistic regression models assessing the relationship between disease activity measures (DAS28-CRP), functional capacity (health assessment questionnaire (HAQ)), selected demographic and social factors (occupation, education, income, marital status, race, gender, age, and BMI), and clinical/laboratory variables. Results The analyses included 729 patients with baseline DAS28-CRP and social/demographic data. The mean age at enrollment was 59.5 (Standard Deviation (SD) = 12.7) years, 78% were female, and the median RA disease duration was 9.8 (Interquartile Range (IQR): 3.7, 19.1) years. We dichotomized the DAS28-CRP score and defined scores above or below 3.1 as high versus low RA disease activity. Most patients with high RA disease activity (N = 326, 45%) had less than a college degree (70%), were not working/retired/disabled (71%), and had an annual income under $50 K (55%). We found that higher body mass index (BMI) (Odds Ratio (OR) = 1.04, 95% CI: 1.01—1.08), longer disease duration (> 2 and

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn’s disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association.

Background: It has been proved that rheumatoid arthritis (RA) patients have high incidence of atrial fibrillation (AF). Nevertheless, whether they have causal relevance is uncertain. This study aimed to explore and verify the authenticity of causal relationship between RA and AF using Mendelian randomization (MR). Methods: The genome-wide association study (GWAS) summary data from Biobank Japan Project (BBJ) (RA, 4199 cases and 208,254 controls) were regarded as exposure data and the GWAS data from European Bio-informatics Institute database (EBI) (AF, 15,979 cases and 102,776 controls) as outcome data. The causal effect was appraised by the inverse variance weighted (IVW) method, MR-Egger regression, and weighted median estimator. MR-robust adjusted profile score (MR-RAPS) method was delivered to examine the robustness of causal relationship and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) method to control horizontal (directional) pleiotropy. Results: The results indicated that RA increased the risk of AF (IVW, the odds ratio (OR) = 1.060; 95% confidence interval (CI), 1.028 to 1.092; p = 1.411 × 10−4; weighted median, OR = 1.046, 95% CI, 1.002 to 1.093, p = 0.047). The MR analysis also showed this causal effect through all four IVW methods with various statistical algorithms. Both MR-RAPS and MR-PRESSO supported the causality of RA and AF. Also, the MR-PRESSO result indicated the absence of apparent pleiotropy. Conclusion: There is a causal association between RA and AF. RA patients are genetically more vulnerable to AF. This study may contribute to further exploring early clinical prevention and fundamental mechanism of AF in patients with RA. Key Points • We provided some genetic evidence for the causal link between rheumatoid arthritis (RA) and atrial fibrillation (AF) with multiple Mendelian randomization (MR) methods. • RA patients were genetically more vulnerable to AF. • This study partly shed light on latent fundamental mechanisms underlying RA-induced AF and inspired future studies on RA-AF relationship. [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of individualized treatment strategy based on imaging evaluation in patients with rheumatoid arthritis (RA). Methods: Eighty patients with RA of the wrist treated in the Second Affiliated Hospital of Nanjing Medical University, China from January 2018 to December 2022 were assigned to control and study groups. Conventional methods were used for treating control subjects, based on RA laboratory index results, while the study group received individualized treatment based on RA laboratory index results and results of imaging evaluation. Before and after treatment, serum levels of rheumatoid factor (RF) and C-reactive protein (CRP) were assayed using immunoturbidimetry. Erythrocyte sedimentation rate (ESR) was determined by Wei method. Imaging examination - ultrasound or magnetic resonance imaging (MRI) - was carried out in study group before and after treatment. Disease activity score 28 (DAS28) and score on the visual analogue scale (VAS) were evaluated before and after treatment, and the curative effect in the two groups was compared based on curative effect evaluation. Results: In both groups, post-treatment values of RF, CRP and ESR were lower than the corresponding pre-treatment levels, but were significantly smaller in study group (p < 0.05). The DAS28 and VAS scores of the two groups after treatment were significantly lower (p < 0.05) than the pret-reatment levels, but the DAS28 and VAS scores were significantly lower in study group (p < 0.05). Treatment efficacy in study group (95.0 %) was significantly higher than in control patients (77.5 %, p = 0.0476). The results of imaging indicators showed significantly reduced post-treatment synovial thickness and joint effusion in study group patients when compared with control patients (p < 0.01). Conclusion: Individualized treatment strategy for RA patients based on imaging results enhances curative effectiveness, reduces disease activity, relieves pain, and improves the quality of life of patients. [ABSTRACT FROM AUTHOR]

It is acknown that Rheumatoid inflammation is a chronic systemic autoimmune disease developing on the background of infection. Damages mainly the heart, blood vessels, musculoskeletal system and other internal organs. Multiple joints may be affected, primarily the knee, ankle and elbow undergoing destruction leads to pain, mainly symmetrical. Damaged joints swollen and skin in these foci reddens; joint morning stiffness lasts for an hour or more, this sign is accompanied by low fever and fatigue. As a result of the rheumatic process, the heart is damaged, leading to cardiovascular manifestations. Analysis of blood parameters allows the severity of the disease to be determined based on a relatively new method using Das28. The obtained results for ESR and CRP are used to calculate DAS28, which also allows monitoring of RA treatment. Most patients with rheumatoid arthritis (RA) are seropositive—they have abnormally high levels of rheumatoid factor (RF) or anti-citrullinated peptide antibodies (anti-CPP) in the blood. The article examines aspects of synthetic, chemical and alternative medicine impact on treating patients with RA as well. The article discusses comparative aspects of pharmacological and herbal medicine in the therapeutics. According to the literature, patients who have not received the expected results after treatment with pharmacological preparations successfully use herbal remedies as a means of body restoring and healing. To date, the success of traditional medicine is ahead of those of conventional using synthetic drugs. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to evaluate the optic nerve, macula, and choroidal changes in both rheumatoid arthritis (RA) and primary Sjögren’s syndrome (SjS) patients, and to compare these findings with age-matched healthy volunteers. Methods: This study included 46 RA patients, 33 primary SjS patients, and 37 age-matched healthy volunteers. All of the patients underwent a thorough ophthalmological examination, during which measurements of the retinal nerve fiber layer (RNFL), ganglion cell layer(GCL), and subfoveal choroidal thickness (CT) were taken using OCT (optical coherence tomography). The measurements taken from the right eye of each patient were used to compare among the groups. Results: RNFL thickness in superior quadrant was found to be statistically significantly thinner in the eyes with RA when compared to the control group (p = 0.022). In the nasal quadrant, the RNFL thickness was significantly thinner in patients with primary SjS compared to healthy individuals (p = 0.036). Also, the temporal quadrant RNFL was significantly thinner in RA patients than in the primary SjS patients (p = 0.033). GCL thickness was observed to be thinner in all quadrants of both RA and primary SjS groups compared to the control group. However, the difference was not found to be statistically significant. Subfoveal CT was observed to be thicker in RA and SjS groups compared to the control group, but this difference was also not statistically significant. Conclusion: Systemic autoimmune diseases like RA and primary SjS can lead to a decrease in RNLF and GCL thickness, which can impair visual acuity even in the absence of ocular symptoms. Therefore, monitoring changes in the optic nerve, retina, and choroid layer are crucial in these patients. [ABSTRACT FROM AUTHOR]

Copyright of Revista Latinoamericana de Hipertension is the property of Revista Latinoamericana de Hipertension and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Latinoamericana de Hipertension is the property of Revista Latinoamericana de Hipertension and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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Introduction: Baricitinib, a JAK1/JAK2 inhibitor, is approved for treatment of moderate-to-severe rheumatoid arthritis (RA) in China. This single-arm, prospective, multi-center, post-marketing safety study (PMSS) evaluated the safety and effectiveness of baricitinib in Chinese patients. Methods: This study included adult patients with moderate-to-severe active RA who received baricitinib over periods of approximately 12 and 24 weeks. The primary endpoint was safety, defined as week 12 adverse event (AE)/serious AE incidence. Secondary endpoints were week 24 safety and effectiveness (disease activity score with 28 joints/C-reactive protein [DAS28-CRP] and simplified/Clinical Disease Activity Index [SDAI/CDAI]). Results: Safety analyses included 667 patients (female, 82.3%; mean age, 53.3 years; mean RA duration, 86.9 months); 106/667 (15.9%) were 65–74 years old and 19/667 (2.8%) were ≥ 75 years old; 87.0% received baricitinib 2 mg QD. Total exposure was 262.1 patient-years (PY). At week 12, AEs had occurred in 214 (32.1%; exposure-adjusted incidence rate [EAIR], 172.5 per 100 PY) patients (serious AEs: 22 [3.3%; EAIR, 15.0]). At week 24, AEs had occurred in 250 (37.5%; EAIR, 125.9) patients (serious AEs: 28 [4.2%; EAIR, 10.9]). Two patients (0.3%) died (of pneumonia and unknown cause); EAIR for death, 0.77. Serious infection occurred in 1.2% of patients (EAIR, 3.1). Hepatotoxicity occurred in 3.4% of patients (EAIR, 9.0). No patients met potential Hy's law laboratory criteria (alanine/aspartate aminotransferases ≥ 3 × upper limit of normal (ULN) and total bilirubin ≥ 2 × ULN). Malignancy occurred in one patient. No patients experienced venous thromboembolism (VTE) or major adverse cardiovascular events (MACE). At week 24, 52.4%, 27.5%, and 27.6% of patients achieved remission per DAS28-CRP, SDAI, and CDAI, respectively. Conclusions: This PMSS investigated the safety and effectiveness of baricitinib in clinical practice in China. No VTE/MACE or new safety signals were reported and there was promising effectiveness, supporting the use of baricitinib in Chinese patients with moderate-to-severe active RA. Trial Registration: EU PAS Register: EUPAS34213. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematopoiesis through its receptor complex. In this review, we first describe the characteristics of OSM and its receptor, and the biological functions of OSM signaling. Subsequently, we discuss the possible roles of OSM in the development of RA from clinical and basic research perspectives. Finally, we summarize the progress of clinical studies targeting OSM for the treatment of RA. This review provides researchers with a systematic understanding of the role of OSM signaling in RA, which can guide the development of drugs targeting OSM for the treatment of RA. [ABSTRACT FROM AUTHOR]

Urine-derived stem cells (UdSCs) possess a remarkable anti-inflammatory and immune-modulating activity. However, the clinical significance of UdSCs in autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is yet to be explored. Hence, we tested the UdSCs response to an articular RA microenvironment. To simulate the inflamed RA joint more authentically in vitro, we treated cells with rheumatoid synovial fluids (RASFs) collected from RA patients, serum deprivation, acidosis (pH 7.0 and 6.5), and their combinations. Firstly, the RASFs pro-inflammatory status was assessed by cytokine quantification. Then, UdSCs were exposed to the RA environmental factors for 48 h and cell proliferation, gene expression and secretion of immunomodulatory factors were evaluated. The immunosuppressive potential of pre-conditioned UdSCs was also assessed via co-cultivation with activated peripheral blood mononuclear cells (PBMCs). In all experimental conditions, UdSCs' proliferation was not affected. Conversely, extracellular acidosis considerably impaired the viability/proliferation of adipose tissue-derived stem cells (ATSCs). In the majority of cases, exposure to RA components led to the upregulated expression of IL-6, TSG6, ICAM-1, VCAM-1, and PD-L1, all involved in immunomodulation. Upon RASFs and acidic stimulation, UdSCs secreted higher levels of immunomodulatory cytokines: IL-6, IL-8, MCP-1, RANTES, GM-CSF, and IL-4. Furthermore, RASFs and combined pretreatment with RASFs and acidosis promoted the UdSCs-mediated immunosuppression and the proliferation of activated PBMCs was significantly inhibited. Altogether, our data indicate that the RA microenvironment certainly has the capacity to enhance UdSCs' immunomodulatory function. For potential preclinical/clinical applications, the intra-articular injection might be a reasonable approach to maximize UdSCs' therapeutic efficiency in the RA treatment. [ABSTRACT FROM AUTHOR]

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease featuring an abnormal immune microenvironment and resultant accumulation of hydrogen ions (H+) produced by activated osteoclasts (OCs). Currently, clinic RA therapy can hardly achieve sustained or efficient therapeutic outcomes due to the failures in generating sufficient immune modulation and manipulating the accumulation of H+ that deteriorates bone damage. Herein, a highly effective immune modulatory nanocatalytic platform, nanoceria‐loaded magnesium aluminum layered double hydroxide (LDH‐CeO2), is proposed for enhanced immune modulation based on acid neutralization and metal ion inherent bioactivity. Specifically, the mild alkaline LDH initiates significant M2 repolarization of macrophages triggered by the elevated antioxidation effect of CeO2 via neutralizing excessive H+ in RA microenvironment, thus resulting in the efficient recruitment of regulatory T cell (Treg) and suppressions on T helper 17 cell (Th 17) and plasma cells. Moreover, the osteogenic activity is stimulated by the Mg ion released from LDH, thereby promoting the damaged bone healing. The encouraging therapeutic outcomes in adjuvant‐induced RA model mice demonstrate the high feasibility of such a therapeutic concept, which provides a novel and efficient RA therapeutic modality by the immune modulatory and bone‐repairing effects of inorganic nanocatalytic material.

Inhibition of inflammation-related NF-κB and MAPK activation could treat rheumatoid arthritis (RA). Previously, some fluorine-substituted 3,5-bis(aryl)-4-piperidone derivatives (BAPs) exhibited promising anti-inflammatory activity. Herein, interesting structural optimization was carried out and generated thirty-eight dissymmetric fluorine and pyridyl-substituted BAPs (4a-s and 5a-s). They were confirmed by NMR and HRMS. A preliminary structure–activity relationship was summarized and discovered 3,5-CF3 and 3-pyridyl-substituted 4k exhibited less toxicity and higher anti-inflammatory activity. Preliminary mechanistic studies revealed that 4k inhibited Lipopolysaccharide-induced nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) activation by suppressing LPS-induced phosphorylation levels of NF-κB/p65, NF-κB/IκBα, c-Jun N-terminal kinase (JNK), extracellular regulated protein kinases (ERK), and NF-κB/p38 in RAW264.7 cells. In vivo, 4k inhibited the development of inflammation and synovial proliferation in rat joint tissues, significantly decreasing paw swelling and arthritis index in adjuvant-induced arthritis rats. More importantly, 4k did not affect body weight and splenic index values. Overall, 4k showed optimistic anti-RA effects, which may be developed as a potential multifunctional agent for the clinical treatment of RA.