Onset Of Rheumatoid Arthritis Research Articles

Incidence Trends of Rheumatoid Arthritis in Korea for 11 Years (2006–2017)

Background/Objectives: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by joint damage. However, no incidence analyses have been conducted on a Korean population since 2013. We aimed to calculate the incidence of RA and examine trends using complete Korean National Health Insurance Service claims data from 2007. Methods: We used 16 years of Korean NHIS claims data from 1 January 2002 to 31 December 2017. Patients were defined as having RA when diagnosed with ICD-10 codes M05 and M06. We set the 5-year period prior to 2006 as disease-free. Results: From 2007 to 2017, the incidence rate of RA was 35 to 43 per 100,000 individuals. The female-to-male ratio was approximately 3–3.5 to 1. The sex-standardized incidence rate was highest in the 60–69 age group but gradually declined, resulting in a reversal in 2017, with the highest incidence rate observed in the 50–59 age group. The incidence of elderly onset RA (EORA) in individuals aged >60 years exhibited a decreasing trend during the study period (age 60–69, −6.45, 95% CI = −8.27 to −4.62, p < 0.001; age ≥70, −6.09, 95% CI = −7.66 to −4.53, p < 0.001). Conclusions: This study is the first to analyze the incidence trend of RA over an 11-year period. In South Korea, the incidence of RA has shown a decreasing trend since 2011; the same trend was observed in the EORA group. Young-onset RA showed the opposite trend, suggesting that RA is diagnosed earlier, due to the new RA classification criteria.

Uncovering specific genetic-respiratory disease endotypes for rheumatoid arthritis risk.

We aimed to identify specific genetic-respiratory disease endotypes for rheumatoid arthritis (RA) risk. This case-control study used the Mass General Brigham (MGB) and Mayo Clinic (MC) Biobanks for discovery and replication, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex and health record history. Genetic exposures included the top 11 RA risk alleles, and a validated human leucocyte antigen (HLA) genetic risk score (GRS). We identified seven respiratory diseases by codes. Using logistic regression models adjusting for potential confounders, we estimated Rs with 95% CIs for the interactions between genetic and respiratory exposures for RA risk. We identified 653 RA cases and 2607 controls in MGB, and 428 incident RA cases and 1712 non-RA controls in MC (mean age 64, 69% female). Respiratory diseases were associated with an increased risk of RA (OR 1.34, 95% CI 1.05, 1.71). Six out of 11 non-HLA RA risk alleles interacted strongly with specific respiratory diseases for RA risk, including NFKBIE and sinusitis (OR 5.49, 95% CI 1.56, 19.4 MGB; 5.26, 95% CI 2.00, 13.86 MC) and FAM167A and acute sinusitis for seronegative RA (OR 6.00, 95% CI 2.09, 17.24 MGB; 4.90, 95% CI 1.71, 14.1 MC). The RA HLA GRS interacted synergistically with interstitial lung disease for RA risk (OR 5.41, 95% CI 2.71, 10.8 in MC), with DPB1*02:01, DRB1*16:01 and DRB1*04:04 best predicting RA (positive predictive value 61%). Several genetic-respiratory disease interactions strongly drive RA onset. If confirmed, these novel associations may reflect RA endotypes that can facilitate individualised prevention, diagnosis and treatment.

Inflammatory cytokines, metabolites, and rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint destruction. Although the roles of inflammatory cytokines and metabolites in RA pathogenesis have caught a lot of attention, there is a lack of systematic studies, and their causal relationships remain unclear. We conducted a two-step mendelian randomization analysis utilizing genetic data from genome-wide association studies (GWAS) of inflammatory cytokines, metabolites, and RA. The first step assessed the causal effect of 91 inflammatory cytokines and 1400 metabolites on RA risk using inverse variance weighted method, complemented by MR-Egger, weighted median, simple mode and MR-PRESSO to ensure robustness and assess pleiotropy. The second step evaluated the mediation effects of selected metabolites on the relationship between cytokines and RA. The analysis identified 9 inflammatory cytokines, including IL-1α and IL-10, which significantly increase RA risk, while TNF-β exhibited a protective effect. Additionally, 6 metabolites were associated with increased RA risk, including 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE and arachidonate (20:4n6). Conversely, 5 metabolites, such as docosatrienoate (22:3n3) and Cholesterol, were found to reduce RA risk. The mediation analysis revealed that TNF-β may exerts its protective effect through its influence on specific metabolites, and X-24949, which accounted for a -2.58% mediated effect in the TNF-β-RA causal pathway. This study explores the complex interplay between inflammatory cytokines, metabolites, and RA. The findings suggest potential biomarkers for early diagnosis and novel therapeutic targets, particularly those related to lipid metabolites and specific cytokines like TNF-β. Key message What is already known on this topic Inflammatory factors and metabolites are considered to be related to the onset and progression of RA. What this study adds We conducted a MR analysis to identify all inflammatory factors and metabolites associated with RA and calculated the mediation effect of inflammatory cytokines on RA through metabolites. This study contributes to a comprehensive understanding of the pathophysiological processes of RA. How this study might affect research, practice or policy This has laid the groundwork for developing early diagnosis methods and future treatments.

Identification and Experimental Verification of PDK4 as a Potential Biomarker for Diagnosis and Treatment in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by sustained joint inflammation, with an etiology that remains elusive. Achieving an early and precise diagnosis poses significant challenges. This study aims to elucidate the molecular pathways involved in RA pathogenesis by screening genes associated with its occurrence, analyzing the related molecular activities, and ultimately developing more effective molecular-level treatments for RA. Microarray expression profiling datasets GSE1919, GSE10500, GSE15573, GSE77298, GSE206848, and GSE236924 were sourced from the Gene Expression Omnibus (GEO) database. Samples were divided into experimental (RA) and control (normal) groups. Differentially expressed genes (DEGs) were identified using R software packages such as limma, glmnet, e1071 as well as randomForest. Cross-validation of DEGs was conducted using lasso regression and the random forest (RF) algorithm in R software to pinpoint intersecting genes that met the criteria. Among these, one gene was selected as the target for correlation analysis to identify DEGs related to the target gene. Enrichment analysis utilized the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases and Gene Ontology (GO) data. Gene Set Enrichment Analysis (GSEA) was performed to compare the expression levels of the target gene (PDK4) across various biological pathways and functions in groups with high and low expression. The relationship between target gene expression levels and cellular immune function was assessed using the immune function score technique. The discrepancy in immune cell distribution between the control and experimental groups, as well as their correlation with target gene expression levels, was elucidated using CIBERSORT. The relationships between mRNA, lncRNA, and miRNA were depicted in the ceRNA regulation network. The expression levels of the target gene were validated using Western blot and qRT-PCR. In this study, six intersecting genes meeting the criteria were identified through cross-validation, and PDK4 was chosen as the target gene for further investigation. Functional analysis using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that PDK4-associated DEGs are primarily enriched in the PPAR signaling pathway, thereby regulating synovial cell proliferation and migration, ultimately influencing the onset and progression of rheumatoid arthritis (RA). Immune infiltration analysis suggested that eosinophil quantity may influence the progression of RA. Experimental results from PCR and Western blot confirmed the downregulation of PDK4 in the RA group. The significant downregulation of PDK4 expression in patients diagnosed with rheumatoid arthritis (RA) was confirmed. PDK4 may function as a novel regulatory factor in the onset and progression of RA, with potential applications as a diagnostic biomarker for the condition.

A compartmentalized microfluidic platform to investigate immune cells cross-talk in rheumatoid arthritis

The dysregulation of the immune system plays a crucial role in the pathogenesis of manyfold diseases, among which we find rheumatoid arthritis (RA), an autoimmune disease characterized by chronic inflammation in synovial joints, leading to pain and disability. Immune cells such as pro-inflammatory macrophages and T helper 1 (Th1) cells drive the inflammatory cascade. Thus, including immune system inin vitromodels is pivotal to recapitulate and better understand the complex interactions between these immune cell subsets and their secreted mediators. Here, a compartmentalized microfluidic platform is presented, for precise confinement of circulating immune cells in organs-on-chip. The integration of innovative normally-closed sieving valves allows, through minimal waste of biological material, to co-culture different immune cell types (e.g. macrophages and Th1). Moreover, the platform allows to stimulate cell subsets separately, and to assess their cross-talk at desired time points. Functional validation of the platform demonstrates its ability to create stable chemotactic gradients, allowing for induction and evaluation of Th1 cells migration. In a proof-of-concept study, the platform allowed to assess Th1 T cells migration towards pro-inflammatory macrophages, thus replicating a characteristic interaction among immune cells triggered during RA onset. These results thus support the suitability of the platform to study immune cells cross-talk and migration phenomena, being potentially applicable to a manyfold immune cell mechanisms, both involved in RA progression and in different immune-mediated pathologies.

Dynamics of the gut microbiome in individuals at risk of rheumatoid arthritis: a cross-sectional and longitudinal observational study

ObjectivesThis work aimed to resolve the conflicting reports on Prevotellaceae abundance in the development of rheumatoid arthritis (RA) and to observe structural, functional and temporal changes in the gut microbiome...

Progression of TMJ disorders in patients with rheumatoid arthritis

Relevance. The literature highlights the significant impact of rheumatoid arthritis (RA) on the onset of musculoskeletal dysfunction symptoms in the temporomandibular joint (TMJ). However, the risk factors that influence the clinical manifestations of TMJ disorders in RA patients remain insufficiently explored.Objective: To examine the impact of rheumatoid arthritis on the onset and progression of TMJ disorders.Materials and methods. At the Dental Clinic of the Central Research Institute of Stomatology and Maxillofacial Surgery, 180 patients from St. Petersburg State Clinical Rheumatology Hospital No. 25, diagnosed with rheumatoid arthritis, were examined. Standard clinical assessments and detailed medical history collection were performed.Results. Patients with long-standing RA (over 5 years) were more likely to experience TMJ disorder symptoms, with a relative risk of 1.342 (95% CI) [1.106; 1.628]. No statistically significant correlation was found between RA activity and TMJ disorders. The symptom pattern varied by timing: prior to RA, patients predominantly experienced TMJ clicking and crepitus (66%); during RA onset, pain and restricted jaw movement were more common (80% and 72%, respectively). After RA manifestation, pain became the dominant symptom, though its intensity diminished over time (to 60%).Conclusions. The duration of RA has a notable impact on both the frequency and nature of TMJ disorder symptoms. While RA treatment reduces symptom intensity over time, their frequency remains high.

The role of non-coding RNAs in fibroblast-like synoviocytes in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by synovial hyperplasia, and fibroblast-like synoviocytes (FLSs) constitute the majority of cells in the synovial tissue, playing a crucial role in the onset of RA. Dysregulation of FLSs function is a critical strategy in treating joint damage associated with RA. Non-coding RNAs, a class of RNA molecules that do not encode proteins, participate in the development of various diseases. This article aims to review the progress in the study of long non-coding RNAs, microRNAs, and circular RNAs in FLSs. Non-coding RNAs are involved in the pathogenesis of RA, directly or indirectly regulating FLSs' proliferation, migration, invasion, apoptosis, and inflammatory responses. Furthermore, non-coding RNAs also influence DNA methylation and osteogenic differentiation in FLSs. Therefore, non-coding RNAs hold promise as biomarkers for diagnosing RA. Targeting non-coding RNAs in FLSs locally represents a potential strategy for future therapies in RA.

A Novel Etanercept-loaded Nano-emulsion for Targeted Treatment of Inflammatory Arthritis via Draining Lymph Node.

Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD), and the global incidence rate is 0.5 ~ 1%. Existing medications might reduce symptoms, however, there is no known cure for this illness. Etanercept (EN) can competitively inhibit TNF-α binding to the TNF receptor on the cell surface to treat RA. However, subcutaneous injection of free EN predisposes to systemic distribution and induces immune system hypofunction. Draining lymph nodes (LNs) play a significant role in the onset, maintenance, and progression of RA as they are the primary sites of aberrant immune response and inflammatory cytokine production. The purpose of this study was to successfully treat RA with etanercept by encapsulating it in nanoemulsions (NEs/EN) and then delivering it specifically to draining LNs. The EN-loaded NEs were prepared by high-pressure homogenization method and modified with DSPE-mPEG2000 and Ca(OH)2. A novel nano-emulsion (NE) was constructed to deliver EN (NE/EN) to RA-draining LNs. To decrease aggregation and load EN, DSPE-mPEG2000 and Ca(OH)2 were successively decorated on the surface of the lipid injectable emulsions. The hydrodynamic diameter and morphology of NEs/EN were investigated by using a laser particle size analyzer and transmission electron microscopy, respectively. The in vivo fluorescence imaging system was used to study the in vivo LN targeting ability of the formulation. In the therapeutic experiment, NEs/EN was subcutaneously administrated to inhibit the development of the mouse arthritis model. Circular dichroism spectrum and L929 cell experiment confirmed that NEs encapsulation had no impact on the biological activity of EN. In vivo investigation on collagen-induced arthritis (CIA) mouse model showed that NEs/EN have good inguinal lymph node targeting capabilities, as well as, anti-inflammatory effect against RA. Compared with the free group, the paw thickness and arthritic score in NEs/EN group were significantly alleviated. Moreover, the concentration of pro-inflammatory cytokines TNF-α and IL-1β in NEs/EN-treated mice was lower than that in free EN. NEs/EN effectively improve the effectiveness of EN in the treatment of RA. Our work provides an experimental foundation for expanding the clinical application of EN.

The Role of MicroRNAs and Stem cells in Rheumatoid Arthritis: A Therapeutic and Diagnostic Approach.

In autoimmune illnesses like Rheumatoid Arthritis (RA), the synovium is constantly inflamed, and joints are ruptured. It is becoming increasingly clear that stem cells, especially notably mesenchymal stem cells (MSCs) and microRNAs (miRNAs), play important roles in the onset and amelioration of RA. There is mounting evidence from both animal and human studies that suggests a potentially safe and effective method to treat RA and other intractable diseases by reducing chronic inflammation and spurring tissue regeneration through the transplantation of multipotent adult stem cells, such as mesenchymal stromal/stem cells. To control gene expression, which impacts immune cell differentiation and inflammatory pathways, microRNAs (miRNAs) are crucial, even though MSCs can self-renew and modify inflammatory reactions. The pathophysiology of RA is marked by the dysregulation of immunological responses and the proliferation of fibroblast-like synoviocytes, which are linked to the aberrant expression of specific microRNAs (miRNAs). This study mainly aims to examine the therapeutic implications of these microRNAs (miRNAs) in relation to RA, as they can function as diagnostic and prognostic indicators. This study explores the functions of microRNAs (miRNAs) and stem cells in rheumatoid arthritis (RA), drawing attention to the relevance of these biological processes and the potential for creating novel therapeutic strategies to improve patient outcomes.

Targeting Therapeutic Windows for Rheumatoid Arthritis Prevention.

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.

Exploring the pathogenesis of RA through the gut-articular axis-dysbiosis a potential factor.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex etiology. It has been suggested that the pathogenesis of RA begins in the mucosa and then transitions to the joints when many factors interact, including microbial dysbiosis, inflammatory responses, and immune abnormalities at the mucosal site. Data from RA animals and patients suggest there are changes in the mucosal microflora before the onset of RA, and that dysbiosis of the mucosal ecology continues to play a role in the development of arthritis. Microbial dysbiosis of the mucosa reduces the normal barrier function of the intestinal tract, promotes inflammatory reactions in the mucosal areas of the intestines, and then activates the intestinal immune cells abnormally to produce a large number of auto-reactive antibodies that exacerbate arthritis. Current findings do not clarify whether dysbiosis is only a potential trigger for the development of RA. If it is possible to intervene in such microbial changes before the onset of RA, could the clinical symptoms of arthritis be prevented or reduced? Finding new ways to regulate gut flora composition to maintain gut barrier function is an ongoing challenge for the prevention and treatment of RA.

Mechanisms of age-related Treg dysfunction in an arthritic environment

Rheumatoid arthritis (RA) is an autoimmune disease characterized by a polyarticular synovitis. In recent years, elderly onset rheumatoid arthritis (EORA) has been increasing. Treg cells in RA have been reported to be dysfunctional, but the relationship between aging and their functional changes is unclear. Here, we found that Treg cells from EORA patients had increased percentages, but decreased activity compared to those from younger onset RA (YORA) patients. In experiments using arthritis model mice, decreased suppressive function and oxygen consumption rate (OCR) were observed in Treg cells only from old arthritic mice. Furthermore, type I interferon (IFN) signaling was upregulated in Treg cells from old GIA mice, and IFN-β decreased the suppressive function of Treg cells. Our findings demonstrate that increased type I IFN signaling in old Treg cells is induced only in the arthritic environment and relates to decreased suppressive function of Treg cells, gets involved in EORA.

Anti-CCP Antibodies in Unaffected First-Degree Relatives of Rheumatoid Arthritis Patient

Introduction: Rheumatoid arthritis (RA) is perhaps the most common inflammatory arthritis, affecting 0.5% to 1% of the general population worldwide. Environmental and genetic influences are important risk factors for pathogenesis of RA. First-degree relatives (FDRs) of RA patients sharing genetic and environmental risk factors for RA may represent as pre-RA state. Since anti-CCP antibody appears years before the onset of RA, it can be used to estimate risk-potential for future development of RA in unaffected FDRs of RA patient. Objective: To see the serum anti-CCP antibody in unaffected FDRs of RA patients. Materials and Methods: This cross-sectional study was conducted from July 2019 to June 2020 in Department of Biochemistry, Dhaka Medical College, Dhaka. A total number of 50 subjects were selected among which 25 were unaffected FDRs of RA patients and the other 25 were age & gender matched healthy subjects. The related RA patients were selected from Rheumatology outdoor, Department of Rheumatology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and the healthy subjects were taken from the attendants came to the same institute who did not have RA patient in their family. The key variables (age and gender) were recorded and outcome variable (anti-CCP antibody in study subjects) was estimated. Statistical analysis was done by SPSS 26.0 and the significance was defined as p < 0.05. Results: Mean age of the FDRs of RA patient was 31.36 ± 10.51 years and that of healthy subjects was 31.56 ± 8.89 years. Most of the participants were in age group 20-29 years followed by 30-39 years. 4% of FDRs of RA patient were anti-CCP antibody positive and no positive case was recorded in healthy subjects. The median level of anti-CCP antibody in FDRs of RA patient was 0.50 U/mL and that in healthy subjects was 0.09 U/mL. The level of significance (p = 0.002) showed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects, which was even more significant in FDRs of seropositive RA patients. Conclusion: This study revealed that serum anti-CCP antibody level was significantly higher (within normal range) in FDRs of RA patient than in healthy subjects and the proportion of positive anti-CCP antibody was more in FDRs of RA patient than in healthy subjects. Medicine Today 2024, Vol.36 (2): 76-81

Autoantibodies to joint-related peptides as predictive markers in early rheumatoid arthritis.

For better management of rheumatoid arthritis (RA), new biomarkers are needed to predict the development of different disease courses. This study aims to identify autoantibodies against epitopes on proteins in the joints and to predict disease outcome in patients with new onset RA. Sera from new onset RA patients from the Swedish BARFOT and TIRA-2 cohorts (n = 1986) were screened for autoantibodies to selected peptides (JointIDs) in a bead-based multiplex flow immunoassay. Disease outcomes included Boolean remission 1.0, swollen joint count and radiographic destruction. Multivariate logistic regression and zero-inflated negative binomial models that accounted for clinical factors were used to identify JointIDs with the strongest potential to predict prognosis. Boolean remission was predicted with 42% sensitivity and 75% specificity in male patients positive for antibodies to a non-modified collagen type II (COL2) peptide at 12 months. When antibodies to a specific citrullinated cartilage oligomeric protein (COMP) peptide were absent and the patient was in Boolean remission at 6 months, the sensitivity was 13% and the specificity 99%. Positivity for the non-modified COL2 peptide also reduced the frequency of swollen joints by 41% and 33% at 6 and 12 months, respectively. Antibodies to cyclic citrullinated peptides (aCCP) predicted joint destruction with low specificity (58%). Positivity for a COL2 and a glucose-6-phosphate dehydrogenase peptide in citrullinated forms increased specificity (86%) at the expense of sensitivity (39%). Autoantibodies against joint-related proteins at RA diagnosis predict remission with high specificity and, in combination with clinical factors, may guide future treatment decisions.

Ascorbic acid alleviates rheumatoid arthritis by inhibiting the production of autoantibodies

BackgroundAscorbic acid can regulate the function of the immune system. This study aimed to investigate the underlying mechanisms of ascorbic acid in plasma cell differentiation and rheumatoid arthritis (RA).MethodsMice were intraperitoneally injected with either ascorbic acid or an equivalent volume of phosphate-buffered saline (PBS). To elucidate the effects of ascorbic acid on arthritis, we utilized a collagen induced arthritis mouse model (CIA). To investigate the effects of ascorbic acid on antibody response, mice were immunized with (4-Hydroxy-3-nitrophenylacetyl)-Ficoll (NP-Ficoll) or (4-hydroxy-3-nitrophenyl) acetyl-keyhole limpet hemocyanin (NP-KLH) to elicit a T-cell independent (TI) or T-cell dependent (TD) antibody response. To clarify the ability of ascorbic acid on plasma cell production, we tracked the B cell differentiation fate on the NP-specific B1-8hi BCR transgenic background.ResultsAscorbic acid-injected mice demonstrated significantly delayed disease incidence and decreased disease severity compared to PBS-injected mice. Ascorbic acid can reduce the titers of autoantibodies in both arthritis and lupus mice models. Ascorbic acid can significantly reduce the number of plasma cells and the production of antigen-specific antibodies in TI and TD antibody response. In addition, ascorbic acid can disrupt the antibody affinity maturation. Through B1-8hi adoptive transfer experiments, it has been demonstrated that ascorbic acid restrains B cell differentiation into plasma cells in a cell-intrinsic manner. After in-depth exploration, we found that ascorbic acid can block the cell cycle of B cells and promote cell apoptosis. Mechanistically, ascorbic acid inhibited the production of autoreactive plasma cells by inhibiting the Stat3 signaling pathway.ConclusionOur study demonstrates that ascorbic acid has the ability to suppress the generation of autoreactive plasma cells, diminish the production of autoantibodies, and consequently delay the onset of rheumatoid arthritis.

Onset of Rheumatoid Arthritis with eye manifestations (clinical case report)

Objective. Rheumatoid Arthritis may onset with ocular manifestations. The purpose of our work was presentation of clinical case of the onset of rheumatoid arthritis with an eye lesion.Materials and methods. A clinical case of rheumatoid arthritis with an atypical onset was analyzed. As well, a search and review of relevant literature was performed.Results. Patient with rheumatoid arthritis got bilateral ulcerous keratitis, refractory to conventional treatment and complicated by bilateral corneal perforation with iris prolapse. Due to the atypical clinical course of ophthalmic lesions being insusceptible of medical treatment, the patient was examined further. Laboratory immunological workup revealed positive rheumatoid factor, anti-CCP and anti-MCV antibodies. The typical symmetric presentation of arthritis developed 8 months after the onset of ophthalmic disorders. Baseline therapy of rheumatoid arthritis has demonstrated efficacy both in controlling the joint manifestations and preventing relapse of keratitis.Conclusion. The development of eye syndrome may precede articular manifestation of rheumatoid arthritis. While managing patients with recurrent bilateral keratitis, rheumatologic pathology should be suspected.

Galangin: A Promising Flavonoid for the Treatment of Rheumatoid Arthritis-Mechanisms, Evidence, and Therapeutic Potential.

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by progressive joint inflammation and damage. Oxidative stress plays a critical role in the onset and progression of RA, significantly contributing to the disease's symptoms. The complex nature of RA and the role of oxidative stress make it particularly challenging to treat effectively. This article presents a comprehensive review of RA's development, progression, and the emergence of novel treatments, introducing Galangin (GAL), a natural flavonoid compound sourced from various plants, as a promising candidate. The bioactive properties of GAL, including its anti-inflammatory, antioxidant, and immunomodulatory effects, are discussed in detail. The review elucidates GAL's mechanisms of action, focusing on its interactions with key targets such as inflammatory cytokines (e.g., TNF-α, IL-6), enzymes (e.g., SOD, MMPs), and signaling pathways (e.g., NF-κB, MAPK), which impact inflammatory responses, immune cell activation, and joint damage. The review also addresses the lack of comprehensive understanding of potential treatment options for RA, particularly in relation to the role of GAL as a therapeutic candidate. It highlights the need for further research and clinical studies to ascertain the effectiveness of GAL in RA treatment and to elucidate its mechanisms of action. Overall, this review provides valuable insights into the potential of GAL as a therapeutic option for RA, shedding light on its multifaceted pharmacological properties and mechanisms of action, while suggesting avenues for future research and clinical applications.

Redefinition of Synovial Fibroblasts in Rheumatoid Arthritis.

The breakdown of immune tolerance and the rise in autoimmunity contribute to the onset of rheumatoid arthritis (RA), driven by significant changes in immune components. Recent advances in single-cell and spatial transcriptome profiling have revealed shifts in cell distribution and composition, expanding our understanding beyond molecular-level changes in inflammatory cytokines, autoantibodies, and autoantigens in RA. Surprisingly, synovial fibroblasts (SFs) play an active immunopathogenic role rather than remaining passive bystanders in RA, with notable alterations in their subpopulation distribution and composition. This study examines these changes in SF heterogeneity, assesses their impact on RA progression, and elucidates the immune characteristics and functions of SF subsets in the RA autoimmunity, encompassing both intrinsic and adaptive immunity. Additionally, this review discusses therapeutic strategies targeting immune SF subsets, highlighting the potential of future interventions in SF phenotypic reprogramming. Overall, this review redefines the role of SFs in RA and suggests targeting SF phenotypic reprogramming and its upstream molecules as a promising therapeutic approach to restore immune balance and modulate immune tolerance in RA.

Fine Particulate Matter Components and Risk of Rheumatoid Arthritis: A Large General Canadian Open Cohort Study.

Exposure to fine particulate matter (PM2.5) has been linked to many diseases. However, it remains unclear which PM2.5 chemical components for these diseases, including rheumatoid arthritis (RA), are more harmful. This study aimed to assess potential associations between PM2.5 components and RA and quantify the individual effects of each chemical component on RA risk. An open cohort of 11,696,930 Canadian adults was assembled using Ontario administrative health data from January 2007 onward. Individuals were followed until RA onset, death, emigration from Ontario, or the end of the study (December 2019). Incident RA cases were defined by physician billing and hospitalization discharge diagnostic codes. The average levels of PM2.5 components (ammonium, black carbon, mineral dust, nitrate, organic matter, sea salt, and sulfate) for 5 years before cohort entry were assigned to participants based on residential postal codes. A quantile g-computation and Cox proportional hazard models for time to RA onset were developed for the mixture of PM2.5 components and environmental overall PM2.5, respectively. We identified 67,676 new RA cases across 130,934,256 person-years. The adjusted hazard ratios for the time to RA onset were 1.027 and 1.023 (95% confidence intervals 1.021-1.033 and 1.017-1.029) per every decile increase in exposures to all seven components and per 1 μg/m3 increase in the overall PM2.5, respectively. Ammonium contributed the most to RA onset in the seven components. Exposure to PM2.5 components was modestly associated with RA risk. Public health efforts focusing on specific components (eg, ammonium) may be a more efficient way to reduce RA burden.