Risk Of Arthritis Research Articles

Depression and risk of arthritis: A Mendelian randomization study

AbstractIntroductionObservational studies have found that most patients with arthritis have depression. We aimed to determine the causal relationship between various types of arthritis and depression.MethodsWe conducted a two‐sample bidirectional Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between depression and multiple types of arthritis. The data of our study were derived from the publicly released genome‐wide association studies (GWASs) and the largest GWAS meta‐analysis. MR analysis mainly used inverse‐variance weighted method; supplementary methods included weighted median, weighted mode, and MR‐Egger using MR pleiotropy residual sum and outlier to detect and correct for the presence of pleiotropy.ResultsAfter adjusting for heterogeneity and horizontal pleiotropy, we found that depression was associated with an increased risk of osteoarthritis (OA) (OR = 1.02, 95%CI: 1.01–1.02, p = 2.96 × E − 5). In the reverse analysis, OA was also found to increase the risk of depression (OR = 1.10, 95%CI: 1.04–1.15, p = .0002). Depression only increased the risk of knee OA (KOA) (OR = 1.25, 95%CI: 1.10–1.42, p = 6.46 × E − 4). Depression could potentially increase the risk of spondyloarthritis (OR = 1.52, 95%CI: 1.19–1.94, p ≤ 8.94 × E − 4).ConclusionThere is a bidirectional causal relationship of depression with OA. However, depression only augments the risk of developing KOA. Depression may increase the risk of spondyloarthritis and gout.

Causal relationships between circulating metabolites and rheumatoid arthritis: A mendelian randomization study

BackgroundBlood metabolites serve as pivotal indicators in identifying and predicting the course of rheumatoid arthritis (RA). However, empirical substantiation of a direct causal link between these serum biomarkers and the development of RA is still lacking comprehensive support. MethodIn pursuit of a thorough exploration of the causal links between circulating blood metabolites and RA, we deployed a two-sample Mendelian randomization (MR) approach during our initial investigative phase. This method was utilized to examine the potential connections between 249 distinct circulating metabolites and the prevalence of RA. In the validation phase, we conducted replication analyses with a new metabolic dataset consisting of 123 metabolites. Furthermore, we employed the Mendelian randomization based on Bayesian model averaging (MR-BMA) technique to pinpoint key metabolic characteristics that have significant causal implications. ResultsIn our primary analysis, we found that acetate, acetoacetate and pyruvate exhibited a consistent protective causal association with rheumatoid arthritis, while lactate demonstrated a positive correlation with rheumatoid arthritis risk. It is also noteworthy that a substantial subset of traits related to both saturated and unsaturated fatty acids showed causal influences. Subsequent secondary analyses substantiated these observations, revealing that traits associated with the average number of methylene groups in a fatty acid chain exhibited protective effects. Ultimately, our MR-BMA analyses unveiled that the ratio of polyunsaturated fatty acids (PUFAs) to total fatty acids assumes a paramount role in increasing the susceptibility to rheumatoid arthritis. ConclusionsBy employing systemic MR analyses, our study has successfully generated an all-encompassing atlas elucidating the intricate connections between circulating metabolites and the susceptibility to rheumatoid arthritis. Our results indicate the high unsaturation degree is a dominant risk factors correlated with rheumatoid arthritis.

Sleep duration and the risk of new-onset arthritis in middle-aged and older adult population: results from prospective cohort study in China.

The pain and sleep disorders caused by arthritis are health issues that have been re-emphasized with the aging population. However, the majority of research on arthritis and sleep disorders has focused on cases that have already been diagnosed with arthritis. This research aims to explore the correlation between sleep duration and new-onset arthritis in middle-aged and older adult individuals. Utilizing data from the China Health and Retirement Longitudinal Study from baseline (2011) to the Wave 3 follow-up (2018), we conducted a 7-year longitudinal investigation targeting populations with valid sleep questionnaire records and without arthritis. Sleep duration was assessed from nighttime sleep and daytime nap records. The new-onset of arthritis was determined based on self-reported diagnosis. We employed different logistic regression models to consider the potential impact of sleep duration on arthritis and conducted mediation analyses to assess the involvement of BMI in the association between sleep duration and the new-onset risk of arthritis. Out of the 6,597 individuals analyzed in the cohort, 586 (8.9%) were diagnosed with new-onset arthritis. Median sleep duration was notably shorter in the new-onset arthritis group (6.63 vs. 6.41 h, p < 0.05). There was a notable negative correlation found between new-onset risk of arthritis and sleep duration, with each Interquartile Range (IQR) increment in sleep leading to a 16% risk reduction (OR: 0.864; 95% CI: 0.784-0.954). Stratified analyses revealed BMI as a potential modifier in the sleep-arthritis relationship (P for interaction = 0.05). Mediation analyses further showed that about 3.5% of the association was mediated by BMI. Additionally, the inclusion of sleep duration improved the arthritis predictive power of our model, with an IDI of 0.105 (0.0203, 0.1898) and an NRI of 0.0013 (0.0004, 0.0022) after adding sleep duration to the basic model. In the middle-aged and older adult demographic of China, increased sleep duration is associated with a decreased new-onset risk of arthritis, with BMI potentially playing a role in mediating this connection.

Association of Four VEGFA Gene Variants with Rheumatoid Arthritis Risk: A Meta-analysis and Trial Sequential Analysis.

The association between rheumatoid arthritis (RA) risk and specific variants of the Vascular Endothelial Growth Factor A (VEGFA) gene remains contentious. This study sought to elucidate the correlations between RA risk and several VEGFA gene variants, including VEGFA-634 (rs2010963), VEGFA-C936 (rs3025039), VEGFA-2578 (rs699947), VEGFA-1154 (rs1570360), through a comprehensive meta-analysis. We systematically reviewed literature from the Cochrane Library database, Embase, PubMed, Web of Science, China National Knowledge Infrastructure, and the Wanfang Data Information Service platform to gather relevant case-control studies. Using odds ratio (OR) and 95% confidence interval (95% CI), we analyzed the data to assess potential correlations. Sensitivity analysis and the Egger's test were employed to ensure the results stability and to evaluate potential publication bias. Additionally, trial sequential analysis (TSA) was conducted to validate the findings. Our meta-analysis incorporated ten studies involving 2817 patients and 2855 controls. Results indicated that the AA genotype of VEGFA-1154 (rs1570360) is associated with a reduced risk of RA in the overall population (AG + GG vs AA: P = 0.032 OR = 1.932 95% CI 1.059-3.523). However, no significant association is found for VEGFA-634 (rs2010963), VEGFA-C936 (rs3025039), and VEGFA-2578 (rs699947) variants with RA risk. Subgroup analysis revealed a significant association between the VEGF rs3025039(C936) variant and RA risk in the PCR-RFLP group under the TC vs. CC model. TSA confirmed the sufficiency of the sample size for robust conclusions. These findings suggest that the G allele of VEGFA-1154 (rs1570360) may increase RA risk, whereas the A allele appears to confer a protective effect. This study enhances our understanding of the genetic predispositions to RA and underscores the potential role of VEGFA gene variants in its pathogenesis.

Influence of stress resilience in adolescence on long-term risk of psoriasis and psoriatic arthritis among men: A prospective register-based cohort study in Sweden.

Although stress is considered to be a negative factor for psoriasis, no convincing scientific evidence of this association exists, largely because of difficulties in measuring stress. Stress resilience is the ability to cope with and adapt to stressful events. Stress resilience can be measured in a standardized way and used as a marker for chronic stress. The objective of this study is to investigate whether low stress resilience in adolescence increases the risk for onset of psoriasis and psoriatic arthritis later in life. A cohort of Swedish men (mean age 18.3 years), enrolled in compulsory military service between 1968 and 2005, was created using data from the Swedish Military Service Conscription Register (n = 1,669,422). Stress resilience at conscription was estimated using standardized semi-structured interviews, and was divided into three categories: low, medium and high. The men were followed from conscription until new-onset psoriasis or psoriatic arthritis, death or emigration or at the latest until 31 December 2019. Cox regression models adjusted for confounders at conscription were used to obtain hazard ratios (HRs) with 95% confidence intervals (CIs) for incident psoriasis and psoriatic arthritis. Men in the lowest stress resilience category had an increased risk of psoriasis and psoriatic arthritis (HR 1.31 (95% CI 1.26-1.36) and 1.23 (95% CI 1.15-1.32), respectively), compared with those in the highest stress resilience category. When including only hospitalized patients the HRs for psoriasis and psoriatic arthritis in the lowest stress resilience group were 1.79 (1.63-1.98) and 1.53 (1.32-1.77), respectively. This large, prospective register study suggests that low stress resilience in adolescence is associated with an increased risk of incident psoriasis among men. The results indicate that patients with psoriasis have an inherent psychological vulnerability, and highlight the importance of addressing psychological well-being in the management of psoriasis.

Alcohol Exposure and Disease Associations: A Mendelian Randomization and Meta-Analysis on Weekly Consumption and Problematic Drinking.

Alcohol consumption significantly impacts disease burden and has been linked to various diseases in observational studies. However, comprehensive meta-analyses using Mendelian randomization (MR) to examine drinking patterns are limited. We aimed to evaluate the health risks of alcohol use by integrating findings from MR studies. A thorough search was conducted for MR studies focused on alcohol exposure. We utilized two sets of instrumental variables-alcohol consumption and problematic alcohol use-and summary statistics from the FinnGen consortium R9 release to perform de novo MR analyses. Our meta-analysis encompassed 64 published and 151 de novo MR analyses across 76 distinct primary outcomes. Results show that a genetic predisposition to alcohol consumption, independent of smoking, significantly correlates with a decreased risk of Parkinson's disease, prostate hyperplasia, and rheumatoid arthritis. It was also associated with an increased risk of chronic pancreatitis, colorectal cancer, and head and neck cancers. Additionally, a genetic predisposition to problematic alcohol use is strongly associated with increased risks of alcoholic liver disease, cirrhosis, both acute and chronic pancreatitis, and pneumonia. Evidence from our MR study supports the notion that alcohol consumption and problematic alcohol use are causally associated with a range of diseases, predominantly by increasing the risk.

Risk factors and comorbidities for psoriatic arthritis. Literature review

Introduction: Psoriatic arthritis is a chronic disease involving peripheral arthritis, spondylitis, dactylitis (inflammation of the whole digit) and enthesitis. It is a disease equally prevalent in both genders. Psoriatic arthritis coexists with several conditions, including metabolic syndrome, obesity, cardiovascular disease, inflammatory bowel disease, and liver disease. The reciprocal effects of comorbidities with psoriatic arthritis are demonstrated by recent research. There are several risk factors associated with the condition that might hasten or worsen its symptoms. Aim of the Study: The purpose of this paper is to present a thorough analysis of the research that has been done on comorbidities and risk factors for psoriatic arthritis. With an emphasis on changeable elements that might impact the disease's progression, the goal is to illustrate the multifaceted nature of psoriatic arthritis. The intention is also to highlight comorbidities that need to be considered while treating a patient with the illness. Materials and methods: An analysis of papers available in PubMed and Google Scholar was performed using the following key words: psoriatic arthritis, psoriatic arthritis and lifestyle, psoriatic arthritis and comorbidities, psoriatic arthritis and cardiovascular risk, psoriatic arthritis and gastrointestinal diseases, psoriatic arthritis and physical activity, psoriatic arthritis and diet, psoriatic arthritis and alcohol, psoriatic arthritis and smoking. Conclusions: Psoriatic arthritis is a chronic disease that affects many areas of patients' lives. It is critical to consider the connections that exist between this illness and other comorbidities. In order to provide a patient with this ailment with the best care possible, variables that might exacerbate the illness's progression must also be taken into consideration. Patients' mental health should get particular attention, and lifestyle modifications should be promoted.

Arthritis is associated with high nutritional risk among older Canadian adults from the Canadian Longitudinal Study on Aging

This study assessed the association between arthritis, functional impairment, and nutritional risk (NR). Cross-sectional data were from the Canadian Longitudinal Study on Aging, a nationally representative sample of 45–85-year-old community-dwelling Canadians (n = 41,153). The abbreviated Seniors in the Community: Risk Evaluating for Eating and Nutrition II (SCREEN II-AB) Questionnaire determined NR scores (continuous), and high NR (score < 38); the Older American Resources and Services scale measured functional impairment. NR scores and status (low/high) were modelled using multiple linear and logistic regressions, respectively. Analyses adjusted for demographic characteristics, functional impairment, and health (body mass index, self-rated general and mental health). Additional analyses stratified the models by functional impairment. People with arthritis had poorer NR scores (B: − 0.35, CI − 0.48, − 0.22; p < 0.05) and increased risks of high NR (OR 1.11, 95% CI 1.06, 1.17). Among those with functional impairment, the likelihood of high NR was 31% higher in people with arthritis compared to those without arthritis (95% CI 1.12, 1.53). Among those with no functional impairment, the likelihood of high NR was 10% higher in people with arthritis compared to those without (95% CI 1.04, 1.16). These relationships differed based on the type of arthritis. Arthritis is associated with high NR in community-dwelling older adults, both with and without functional impairment. Findings highlight the need for further research on these relationships to inform interventions and improve clinical practices.

Double-quantitative multi-granularity kernel fuzzy rough sets model and its application in rheumatoid arthritis risk assessment

Double-quantitative multi-granularity kernel fuzzy rough sets model and its application in rheumatoid arthritis risk assessment

Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data.

In this commentary, we review clinical data which helps inform individualized benefit-risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.Trial Registration: NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.

Gene Expression Profiling to Unfolded Proteins Response as a Risk Modulator of Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that endoplasmic reticulum (ER)-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including a total of 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the unfolded protein response (UPR)-associated genes (p-eIF2, BCL-2, PERK, ATF4, and BAX) were investigated using real-time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression levels of PERK, BCL-2, p-eIF2, ATF4, and BAX were found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056, and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that the targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Retrospective validation of a rapid Lyme fluorescent immunoassay in differentiating Lyme arthritis from other musculoskeletal presentations in children in a Lyme-endemic region.

Lyme arthritis is a common manifestation of Lyme disease in children, with clinical features overlapping with other causes of acute and chronic joint pain/swelling in children. We have demonstrated that the Sofia IgG is a reliable test to rule in and rule out the diagnosis of Lyme arthritis in children with musculoskeletal presentations in a Lyme-endemic region. When used in conjunction with clinical and laboratory variables routinely considered when differentiating Lyme arthritis from other diagnoses, the Sofia IgG has the potential to fill an important gap in care, especially when acute decision-making is necessary. The Sofia IgG should be included in prospective research studies examining clinical prediction tools to identify children at low risk of septic arthritis.

A review on cardiovascular risk in rheumatoid arthritis

A systemic inflammatory disease known as rheumatoid arthritis (RA) is distinguished by excessive cardiovascular disease (CVD) morbidity and death. Traditional CV risk factors may partially contribute to CV disease in RA. Shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, changes in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction are some of the mechanisms that link RA and CVD. The detailed pathogenetic pathway by which this association between RA and CVD might be explained is still not entirely known. It is crucial for controlling cardiovascular risk in people with RA. Optimizing care of traditional risk factors in addition to those inherent to RA is necessary to lessen the burden caused by CVD. The potential effect of planned Cardiac risk management in these individuals is highlighted by findings for under diagnosis and inadequate treatment of conventional CVD risk factors in RA. Present cardiovascular standards suggest RA patients to be examined for and treated for CVD risk factors without appropriate treatment goals. Utilizing potent anti-rheumatic medications that can reduce disease activity and treating the conventional CV risk factors should both be part of the therapy of CV risk in RA. There is currently insufficient scientific data to develop therapy targets for RA-related CVD risk factors. Thus, more study is required on the traditional CVD risk factor screening and management in RA patients.

Association between serum antinuclear antibody and rheumatoid arthritis.

The relationship between serum antinuclear antibody (ANA) and rheumatoid arthritis (RA) remains unknown. Therefore, we aimed to evaluate whether serum ANA was associated with an increased risk of RA in a case-control study. Patients with rheumatoid arthritis hospitalized at Shandong Provincial Hospital from January 2018 to December 2022 were recruited as the case group, and patients with other types of arthritis and healthy people at the same time were taken as the control group. Antinuclear antibody (ANA) was detected by indirect immunofluorescence assays. Propensity score matching was employed to construct a cohort of patients exhibiting comparable baseline characteristics. The relationship between serum ANA and the risk of rheumatoid arthritis was analyzed by logistic regression analysis. A total of 1,175 patients with RA and 1,662 control subjects were included in this study. After adjusting for potential confounding factors in the propensity-score matched cohort, the risk of RA gradually increased with rising of ANA titers. When ANA titers were divided into three groups (1:100, 1:320, and 1:1,000), the OR (95% CI) for ANA titers from low to high was 3.95 (3.01, 5.18), 16.63 (9.44, 29.30), and 17.34 (9.53, 31.54), respectively, compared to those when ANA was negative. The ANA patterns closely related to the occurrence of RA include nuclear homogeneous, nuclear speckled, and cytoplasmic speckled. Among them, the positive rate of nuclear homogeneous was the highest, which accounted for 42.64%. The OR (95% CI) of ANA patterns including nuclear homogeneous, nuclear speckled, and cytoplasmic speckled was 16.81 (11.46, 24.65), 3.40 (2.49, 4.63), and 3.09 (1.77, 5.40), respectively. There was a curve relation between ANA titer and RA, and the higher the ANA titer, the higher the probability of RA. However, there was no statistical difference in probability of RA for 1:320 versus 1:1,000 ANA titers. The most important kind of ANA pattern in the blood of RA patients was nuclear homogeneous. These findings suggest that ANA may be a novel risk marker for RA.

Associations of per- and polyfluoroalkyl substances (PFAS) and their mixture with risk of rheumatoid arthritis in the U.S. adult population

BackgroundPer- and polyfluoroalkyl substances (PFAS) are known environmental contaminants with immunosuppressive properties. Their connection to rheumatoid arthritis (RA), a condition influenced by the immune system, is not well studied. This research explores the association between PFAS exposure and RA prevalence.MethodsThis research utilized data from the NHANES, encompassing a sample of 10,496 adults from the 2003–2018 cycles, focusing on serum levels of several PFAS. The presence of RA was determined based on self-reports. This study used multivariable logistic regression to assess the relationship between individual PFAS and RA risk, adjusting for covariates to calculate odds ratios (ORs). The combined effects of PFAS mixtures were evaluated using BKMR, WQS regression, and quantile g-computation. Additionally, sex-specific associations were explored through stratified analysis.ResultsHigher serum PFOA (OR = 0.88, 95% CI: 0.79, 0.98), PFHxS (OR = 0.91, 95% CI: 0.83, 1.00), PFNA (OR = 0.87, 95% CI: 0.77, 0.98), and PFDA (OR = 0.89, 95% CI: 0.81, 0.99) concentration was related to lower odds of RA. Sex-specific analysis in single chemical models indicated the significant inverse associations were only evident in females. BKMR did not show an obvious pattern of RA estimates across PFAS mixture. The outcomes of sex-stratified quantile g-computation demonstrated that an increase in PFAS mixture was associated with a decreased odds of RA in females (OR: 0.76, 95% CI: 0.62, 0.92). We identified a significant interaction term of the WQS*sex in the 100 repeated hold out WQS analysis. Notably, a higher concentration of the PFAS mixture was significantly associated with reduced odds of RA in females (mean OR = 0.93, 95% CI: 0.88, 0.98).ConclusionsThis study indicates potential sex-specific associations of exposure to various individual PFAS and their mixtures with RA. Notably, the observed inverse relationships were statistically significant in females but not in males. These findings contribute to the growing body of evidence indicating that PFAS may have immunosuppressive effects.

Increased serum adipokines are associated with sarcopenia in non-obese women with rheumatoid arthritis.

Large cohort studies have disclosed the association between obesity and rheumatoid arthritis (RA) risk. The sarcopenia prevalence in RA patients can be up to 31%. However, there is little information linking adipokines to sarcopenia in RA, so this study aimed to investigate whether adipokines were indeed involved in secondary sarcopenia in RA with a focus on non-obese females. Sixty-four female patients and 36 controls were included in this study. The serum adipokine levels (leptin and adiponectin) were determined by ELISA kits. The impacts of adipokines on muscle atrophy and potential autophagy were examined in mouse myoblasts, C2C12, upon treatment with recombinant leptin and adiponectin agonist (AdipoRan). Interestingly, serum adiponectin was significantly increased but the ratio of leptin/adiponectin was dramatically decreased in the RA patients with sarcopenia. After normalization by body mass, serum leptin was positively associated but adiponectin was negatively associated with muscle mass respectively, even after adjustment for fat mass. Treating C2C12 cells with leptin and AdipoRan inhibited proliferation of mature myotube respectively, as did treatment with the serum from RA patients. A combination of low leptin and high AdipoRan greatly decreased myogenin, but instead increased MAFbx and MuRF-1 as well as increased Beclin 1, Atg5, and LC3β. Taken together, our study reveals that secondary sarcopenia of RA females may be an imbalance of RA-related, but not obesity-related, increase in adipokine production; additionally, the reduced leptin/adiponectin ratio could be a better indicator in monitoring sarcopenia in non-obese RA females. Moreover, adipokine imbalance may promote muscle atrophy through inducing autophagy.

Expansion of HLA-DR Positive Peripheral Helper T and Naive B Cells in Anticitrullinated Protein Antibody-Positive Individuals At Risk for Rheumatoid Arthritis.

To investigate immune dysregulation in the peripheral blood that contributes to the pre-rheumatoid arthritis (RA) stage of RA development in anticitrullinated protein antibody (ACPA)+ individuals. Using 37 markers by mass cytometry, we investigated peripheral blood mononuclear cells (PBMCs) from ACPA+ at-risk individuals, ACPA+ early untreated patients with RA, and ACPA- controls in the Tokyo Women's Medical University cohort (n = 17 in each group). Computational algorithms, FlowSOM and Optimized t-Distributed Stochastic Neighbor Embedding, were employed to explore specific immunologic differences between study groups. These findings were further evaluated, and longitudinal changes were explored, using flow cytometry and PBMCs from the US-based Targeting Immune Responses for Prevention of RA cohort that included 11 ACPA+ individuals who later developed RA (pre-RA), of which 9 had post-RA diagnosis PBMCs (post-RA), and 11 ACPA- controls. HLA-DR+ peripheral helper T (Tph) cells, activated regulatory T cells, PD-1hi CD8+ T cells, and CXCR5-CD11c-CD38+ naive B cells were significantly expanded in PBMCs from at-risk individuals and patients with early RA from the Tokyo Women's Medical University cohort. Expansion of HLA-DR+ Tph cells and CXCR5-CD11c-CD38+ naive B cells was likewise found in both pre-RA and post-RA time points in the Targeting Immune Responses for Prevention of RA cohort. The expansion of HLA-DR+ Tph cells and CXCR5-CD11c-CD38+ naive B cells in ACPA+ individuals, including those who developed inflammatory arthritis and classified RA, supports a key role of these cells in transition from pre-RA to classified RA. These findings may identify a new mechanistic target for treatment and prevention in RA.

Association Between Composite Dietary Antioxidant Index and the Risk of Endometriosis-Related Rheumatoid Arthritis in Women of Childbearing Age: A Cross-Sectional Study Based on the National Health and Nutrition Examination Survey Database.

To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis (EM)-related rheumatoid arthritis (RA) in women of childbearing age. Using the data from the National Health and Nutrition Examination Survey database, this cross-sectional study included women of childbearing age. The CDAI was obtained by summing the standardized Z-values of the dietary intakes. EM was diagnosed based on a questionnaire-based survey. The outcome of this study was the presence of RA, which was defined by a questionnaire. The associations of CDAI and EM with the risk of RA were determined using weighted logistic analysis. Additive interaction was evaluated using the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S). In total, 3803 patients were included, of which 74 patients (1.99%) were with RA. A lower CDAI [odds ratio (OR): 1.85, 95% confidence interval (CI): 1.12 to 3.04, P= 0.015] and the presence of EM (OR: 3.05, 95% CI: 1.19 to 7.81, P= 0.023) was associated with the risk of RA. The result demonstrated an additive interaction of a lower CDAI and the presence of EM on the risk of RA (OR: 6.19, 95% CI: 2.33 to 16.43, P <0.001, P of trend =0.007). Nevertheless, there was no significant additive interaction after being assessed by the RERI, AP, and S. However, a joint effect of a lower CDAI and EM on the risk of RA (OR: 3.94, 95% CI: 1.35 to 11.51, P= 0.013) was observed. Our study identified EM, and lower CDAI, was related to the risk of RA. Lower CDAI score was also associated with the risk of EM-related RA. This study indicates the importance of antioxidant intake in daily diet for the management of EM-related RA.

Personality and Risk of Arthritis in Six Longitudinal Samples.

Personality traits are broadly related to medical conditions, but there is limited research on the association with the risk of arthritis. This multicohort study examines the concurrent and prospective associations between personality traits and arthritis risk. Participants (N > 45,000) were mostly middle-aged and older adults from 6 established longitudinal cohorts. Baseline assessments of personality traits, covariates (age, sex, education, race, ethnicity, depressive symptoms, body mass index, and smoking), and arthritis diagnosis were obtained in each sample. Arthritis incidence was assessed over 8-20 years of follow-up. The meta-analyses identified an association between higher neuroticism and an increased risk of concurrent (odds ratio = 1.20, 95% confidence interval [CI] = 1.16-1.24; p < .001, I2 = 40.27) and incident (hazard ratio = 1.11, 95% CI = 1.08-1.14; p < .001, I2 = 0) arthritis and between higher conscientiousness and a decreased risk of concurrent (odds ratio = 0.88, 95% CI = 0.86-0.90; p < .001, I2 = 0) and incident (hazard ratio = 0.95, 95% CI = 0.92-0.98; p = .002, I2 = 41.27) arthritis. Higher extraversion was linked to lower risk of concurrent (odds ratio = 0.92, 95% CI = 0.88-0.96; p < .001, I2 = 76.09) and incident (hazard ratio = 0.97, 95% CI = 0.95-0.99; p = .018, I2 = 0) arthritis, and openness was related to lower risk of concurrent arthritis (odds ratio = 0.96, 95% CI = 0.93-0.99; p = .006, I2 = 35.86). Agreeableness was unrelated to arthritis. These associations were partially accounted for by depressive symptoms, body mass index, and smoking. There was no consistent evidence of moderation by age or sex. Findings from 6 samples point to low neuroticism and higher conscientiousness as factors that reduce the risk of arthritis.

Relationships among gut microbiota, plasma metabolites, and juvenile idiopathic arthritis: a mediation Mendelian randomization study.

The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators. Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization. In our MR analysis, a positive correlation was observed between Rikenellaceae and the risk of juvenile idiopathic arthritis, while Dorea showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between Dorea and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%]. Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.