Risk Of Rheumatoid Arthritis Research Articles

Association between Haloperidol use and Risk of Rheumatoid Arthritis.

Association between Haloperidol use and Risk of Rheumatoid Arthritis.

Association of HMGCR inhibition with rheumatoid arthritis: a Mendelian randomization and colocalization study.

The objective of this study was to investigate the association between hydroxymethylglutaryl coenzyme A reductase (HMGCR) inhibition and rheumatoid arthritis (RA) using drug-target Mendelian randomization (MR) and genetic colocalization analyses. Two sets of genetic instruments were employed to proxy HMGCR inhibitors: expression quantitative trait loci (eQTLs) of target genes from the eQTLGen Consortium and genetic variants associated with low-density lipoprotein cholesterol (LDL-C) levels with HMGCR locus from open genome-wide association studies (GWAS). Positive control analyses were conducted on type 2 diabetes and coronary heart disease, and multiple sensitivity analyses were performed. Genetically proxied expression of eQTL was associated with a lower risk of RA (OR=0.996, 95% CI =0.992-0.999, p= 0.032). Similarly, hydroxymethylglutaryl coenzyme A reductase (HMGCR)-mediated low-density lipoprotein cholesterol was negatively associated with risk of RA (OR=0.995, 95% CI =0.991-0.998, p= 0.007) in the inverse variance weighted (IVW) method. Colocalization analysis suggested a 74.6% posterior probability of sharing a causal variant within the SNPs locus (PH4 = 74.6%). A causal relationship also existed between HMGCR-mediated LDL and RA risk factors. The results were also confirmed by multiple sensitivity analyses. The results in positive control were consistent with the previous study. Our study suggested that HMGCR inhibition was associated with an increased risk of RA while also highlighting an increased risk of current smoking and obesity. These findings contribute to a growing body of evidence regarding the adverse effects of HMGCR inhibition on RA risk, calling for further research on alternative approaches using HMGCR inhibitors in RA management.

Exploring the causal relationship between inflammatory cytokines and inflammatory arthritis: A Mendelian randomization study

ObjectivesPrevious studies have reported an association between inflammatory cytokines and inflammatory arthritis, including Ankylosing spondylitis (AS), rheumatoid arthritis (RA), and psoriatic arthritis (PsA). This study aims to explore the causal relationship between inflammatory cytokines and AS, RA, and PsA using Mendelian randomization (MR). MethodsWe conducted a bidirectional two-sample MR analysis using genetic summary data from a publicly available genome-wide association study (GWAS) that included 41 genetic variations of inflammatory cytokines, as well as genetic variant data for AS, RA, and PsA from the FinnGen consortium. The main analysis method used was Inverse variance weighted (IVW) to investigate the causal relationship between exposure and outcome. Additionally, other methods such as MR Egger, weighted median (WM), simple mode, and weighted mode were employed to strengthen the final results. Sensitivity analysis was also performed to ensure the reliability of the findings. ResultsThe results showed that macrophage colony-stimulating factor (MCSF) was associated with an increased risk of AS (OR = 1.163, 95 % CI = 1.016–1.33, p = 0.028). Conversely, high levels of TRAIL and beta nerve growth factor (β-NGF) were associated with a decreased risk of AS (OR = 0.892, 95 % CI = 0.81–0.982, p = 0.002; OR = 0.829, 95 % CI = 0.696–0.988, p = 0.036). Four inflammatory cytokines were found to be associated with an increased risk of PsA: vascular endothelial growth factor (VEGF) (OR = 1.161, 95 % CI = 1.057–1.275, p = 0.002); Interleukin 12p70 (IL12p70) (OR = 1.189, 95 % CI = 1.049–1.346, p = 0.007); IL10 (OR = 1.216, 95 % CI = 1.024–1.444, p = 0.026); IL13 (OR = 1.159, 95 % CI = 1.05–1.28, p = 0.004). Interleukin 1 receptor antagonist (IL-1rα) was associated with an increased risk of seropositive RA (OR = 1.181, 95 % CI = 1.044–1.336, p = 0.008). Similarly, genetic susceptibility to inflammatory arthritis was found to be causally associated with multiple inflammatory cytokines. Lastly, the sensitivity analysis supported the robustness of these findings. ConclusionsThis study provides additional insights into the relationship between inflammatory cytokines and inflammatory arthritis, and may offer new clues for the etiology, diagnosis, and treatment of inflammatory arthritis.

Patient-reported swelling in arthralgia patients at risk for rheumatoid arthritis: is it of value?

Patients with Clinically Suspect Arthralgia (CSA) are at risk for developing Rheumatoid Arthritis (RA). These patients often report joint swelling while this is not objectified by physical examination. To explore the value of patient-reported swelling in CSA, we aimed to determine its association with subclinical joint-inflammation on imaging and RA-development. In two independent, similarly designed CSA-cohorts from the Netherlands, symptomatic patients at risk for RA were studied. At baseline, patients indicated whether they had experienced swelling in hand joints. Subclinical joint-inflammation was assessed with MRI or ultrasound (US). Patients were followed for inflammatory arthritis development. In total, 534 CSA-patients from two independent cohorts were studied, patient-reported swelling was present in 57% in cohort 1, and in 43% in cohort 2. In both cohorts patient-reported swelling was associated with subclinical joint-inflammation. Using MRI, it associated specifically with tenosynovitis (OR 3.7 (95%CI 2.0-6.9)) and when using US with synovitis (OR 2.3 (95%CI 1.04-5.3)). CSA-patients with self-reported swelling at baseline developed arthritis more often, with hazard ratios of 3.7 (95%CI 2.0-6.9) and 3.4 (95%CI 1.4-8.4) in cohort 1 and 2, respectively. This was independent of clinical predictors (e.g. morning stiffness), autoantibody-positivity and US-detected subclinical joint-inflammation. However, when corrected for MRI-detected subclinical joint-inflammation, self-reported swelling was no longer an independent predictor. Patient-reported joint swelling in CSA relates to subclinical joint-inflammation and is an independent risk factor for RA-development, but it is less predictive than the presence of MRI-detected subclinical joint-inflammation.

Diet and Lifestyle Impact on Rheumatoid Arthritis: A Comprehensive Review.

A systemic, inflammatory illness such as rheumatoid arthritis (RA) causes progressive cartilage and bone degradation in addition to joint involvement. Factors related to genetics and environment determine susceptibility to RA. In recent years, an increasing body of research has illuminated the pivotal role of diet and lifestyle in influencing the risk and progression of illnesses. Some nutrients, like polyunsaturated fatty acids, can combat inflammation. They also actas antioxidants, thus protecting against the onset of RA. Conversely, substances like salt and red meat have adverse effects, promoting the development and progression of RA through indirect mechanisms that impact gut microbiota and body composition. As we look ahead, potential supplementary therapies alongside the existing RA treatment regimen may manifest as specific dietary patterns and supplements. Promising candidates include the Mediterranean Diet (MD), vitamin D, and probiotics, which could potentially confer protective benefits. A poor level of education and low socioeconomic status, as well as smoking, an unhealthy diet, and obesity, have all been linked to an increased risk of RA in large epidemiological studies. Additionally, several lifestyle choices affect how well RA responds to antirheumatic medications. A worse treatment outcome is linked, among other things, to smoking, obesity, and insufficient physical activity. Therefore, RA sufferers must be urged to live a healthy lifestyle and eat well.

A novel intergenic variant, rs2004339 A/G, of the gene encoding interleukin-40, C17orf99, is associated with risk of rheumatoid arthritis in Iraqi women

Interleukin-40 (IL-40) is a novel cytokine encoded by the chromosome 17 open reading frame 99 (C17orf99) gene. Recent studies have shown that IL-40 levels are significantly up-regulated in patients with rheumatoid arthritis (RA). However, the association of genetic variants of the C17orf99 gene with the risk of RA has not been investigated. In this case-control study, two intergenic variants, rs2004339 A/G and rs2310998 G/A, were genotyped for the first time in 120 Iraqi women with RA (30 newly diagnosed [ND] and 90 medicated [MD; treated with the tumor necrosis inhibitor etanercept plus methotrexate]) and 110 control women using TaqMan 5′-allele discrimination method. Serum IL-40 levels were also determined using an enzyme-linked immunosorbent assay kit. Multinomial logistic regression analysis was used to analyze rs2004339 and rs2310998 under five genetic models (allele, recessive, dominant, over-dominant, and co-dominant). Results revealed that the mutant A allele (allele model) and the homozygous AA genotype (co-dominant model) of rs2004339 were significantly associated with an increased risk of RA (odds ratio [OR] = 3.37 and 7.44, respectively; corrected probability [pc] < 0.001), while rs2310998 showed no association with RA risk. When comparing the allele and genotype frequencies of rs2004339 and rs2310998 between ND and MD patients, there were no statistically significant differences. Haplotype analysis of the two variants (in the order rs2004339-rs2310998) revealed that haplotypes A-A (OR = 1.72; pc = 0.024) and A-G (OR = 2.85; pc < 0.001) were associated with an increased risk of RA. IL-40 levels (median and interquartile range) were significantly elevated in RA patients compared to controls (29.3 [15.5–41.5] vs. 12.6 [7.4–18.8] pg/mL; p < 0.001). IL-40 levels were not influence by disease duration or disease activity, but the rs2310998 genotypes had an effect; IL-40 levels were significantly higher in women with the AA genotype than in women with the GG genotype (20.1 [12.9–37.1] vs. 15.8 [8.3–22.6] pg/mL; p = 0.006). Regarding medication, IL-40 tended to show elevated levels in ND cases compared to MD cases but without a significant difference. In conclusion, the mutant A allele and the mutant-type AA genotype of the intergenic variant rs2004339 were associated with an increased risk of RA among Iraqi women. Serum IL-40 levels were also elevated in patients, particularly ND patients, and were positively affected by the mutant-type AA genotype. Accordingly, the role of IL-40 in the pathogenesis of RA has been indicated.

Association of Tumor Necrosis Factor Inhibitors with the Risk of Nontuberculous Mycobacterial Infection in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study.

Tumor necrosis factor inhibitors (TNFi) are proposed as a risk factor for nontuberculous mycobacteria (NTM) infection. Limited research investigates NTM infection risk in rheumatoid arthritis (RA) patients treated with TNFi compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), considering other concurrent or prior non-TNFi antirheumatic drugs. We aimed to evaluate the NTM infection risk associated with TNFi using a real-world database. Patients with RA treated with TNFi or csDMARDs between 2005 and 2016 were identified utilizing the Korean National Health Insurance Service database. To minimize potential bias, we aligned the initiation year of csDMARDs for both TNFi and csDMARD users and tracked them from their respective treatment start dates. The association of TNFi with NTM infection risk was estimated in a one-to-one matched cohort using a multivariable conditional Cox regression analysis. In the matched cohort (n = 4556), the incidence rates of NTM infection were 2.47 and 3.66 per 1000 person-year in TNFi and csDMARD users. Compared to csDMARDs, TNFi did not increase the risk of NTM infection (adjusted hazard ratio (aHR) 0.517 (95% confidence interval, 0.205-1.301)). The TNFi use in RA patients was not associated with an increased risk of NTM infection compared to csDMARDs. Nevertheless, monitoring during TNFi treatment is crucial.

Genetic association between interleukin-17 and susceptibility to rheumatoid arthritis

BackgroundThe pathogenesis of rheumatoid arthritis (RA) is an immune imbalance, in which various inflammatory immune cells and pro-inflammatory factors are involved. Interleukin-17 (IL-17), a potent pro-inflammatory cytokine, has been found to have increased expression in the joints of patients with RA compared to healthy individuals. However, the causal relationship between the expression level of IL-17 or IL-17 receptor (IL-17R) and RA remained unknown. In this study, two-sample Mendelian randomization (MR) was used to investigate the causal relationship between IL-17 and RA.MethodsSummary statistics for RA (14,361 RA cases and 43,923 healthy controls) and IL-17 (3,301 samples) were obtained from an available meta-analysis of published genome-wide association studies (GWAS). Relevant single nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. Then we used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality. MR and MVMR analyses progressed mainly using inverse variance weighted (IVW), weighted median (WM), and MR-Egger regression methods, which were applied to the genetic instrumental variables (IVs) of IL-17A/IL-17 RA, IL-17C/IL-17 RC, and IL-17D/IL-17RD and RA. For assessing the robustness of the results, we also carried out a sensitivity analysis to assess heterogeneity and pleiotropy, such as MR-Egger, leave-one-out, and MR pleiotropy residual sum and outlier (MR-PRESSO).ResultsTwo-sample MR Analysis showed the causal relationship between IL-17A/IL-17RA and RA. The presence of genetically high IL-17A/IL-17RA may increase the risk of RA (IL-17A(OR = 1.095; 95% C.I., 0.990-1.210, p.adj = 0.013), IL-17RA(OR = 1.113, 95%CI = 1.006-1.231, p.adj = 0.006)). However, the results indicated that IL-17C/IL-17RC, and IL-17D/IL-17RD demonstrated no causal impact on RA (IL-17C(OR = 1.007, 95%CI = 0.890-1.139, p.adj = 0.152), IL-17RC(OR = 1.006, 95%CI = 0.904-1.119, p.adj = 0.152), IL-17D(OR = 0.979, 95%CI = 0.843-1.137, p.adj = 0.130), IL-17RD(OR = 0.983, 95%CI = 0.876-1.104, p.adj = 0.129)). Furthermore, MVMR analysis shown that IL-17RA(OR = 1.049, 95% CI: 0.997-1.102, p.adj = 0.014) was associated with increased risk of RA. Sensitivity analysis showed no heterogeneity and pleiotropy, suggesting that the above results were robust and reliable.ConclusionThe MR analysis provides evidence that IL-17A/IL-17RA are risk factors for RA. This emphasizes the importance of intervention on IL-17A/IL-17RA in patients with RA. Developing drugs that limit IL-17A may reduce the risk of RA.

Longitudinal reciprocal association between rheumatoid arthritis and chronic obstructive pulmonary disease and mediation of inflammation.

To elucidate the longitudinal reciprocal association between RA and chronic obstructive pulmonary disease (COPD) and the mediating role of systemic inflammation in the association. A total of 403 045 participants from UK Biobank were enrolled in this study. A cross-lagged panel model was used to investigate the longitudinal reciprocal association between RA and COPD. Cox proportional hazards regression and logistic regression models were also conducted to examine the association between baseline RA and COPD during follow-up, and vice versa. Causal mediation analysis was then performed to explore the mediating roles of 160 systemic inflammatory biomarkers in the bidirectional association. At baseline, 4755 (1.2%) and 6989 (1.7%) individuals were diagnosed with RA and COPD, respectively. After adjusting for the covariates, the result of a cross-lagged panel model revealed a bidirectional association between RA and COPD (β = 0.018, P < 0.001 for the RA→COPD path; β = 0.010, P < 0.001 for the COPD→RA path). In the non-COPD population, the risk of future COPD was increased in RA patients [Cox model: hazard ratio (HR) 1.65 (95% CI 1.50, 1.83); logistic model: odds ratio (OR) 1.85 (95% CI 1.66, 2.07)]. In the non-RA population, baseline COPD was associated with a higher risk of RA during follow-up [Cox model: HR 1.67 (95% CI 1.44, 1.92); logistic model: OR 1.70 (95% CI 1.47, 1.97)]. Five inflammatory factors mediated the RA→COPD path and CRP mediated the COPD→RA path (false discovery rate < 0.05). A significant bidirectional association exists between RA and COPD and it is partially mediated by systemic inflammation.

Synovial Tissue Heterogeneity in Japanese Patients With Rheumatoid Arthritis Elucidated Using a Cell-Type Deconvolution Approach.

Recent advances in single-cell RNA sequencing technology have improved our understanding of the immunological landscape of rheumatoid arthritis (RA). We aimed to stratify the synovium from East Asian patients with RA by immune cell compositions and gain insight into the inflammatory drivers of each synovial phenotype. Synovial tissues were obtained from East Asian patients in Japan with RA (n=41) undergoing articular surgery. The cellular composition was quantified by a deconvolution approach using a public single-cell-based reference. Inflammatory pathway activity was calculated by gene set variation analysis, and chromatin accessibility was evaluated using assay of transposase accessible chromatin-sequencing. We stratified RA synovium into three distinct subtypes based on the hierarchical clustering of cellular composition data. One subtype was characterized by abundant HLA-DRAhigh synovial fibroblasts, autoimmune-associated B cells, GZMK+ GZMB+ CD8+ T cells, interleukin (IL)1-β+ monocytes, and plasmablasts. In addition, tumor necrosis factor (TNF)-α, interferons (IFNs), and IL-6 signaling were highly activated in this subtype, and the expression of various chemokines was significantly enhanced. Moreover, we found an open chromatin region overlapping with RA risk locus rs9405192 near the IRF4 gene, suggesting the genetic background influences the development of this inflammatory synovial state. The other two subtypes were characterized by increased IFNs and IL-6 signaling, and expression of molecules associated with degeneration, respectively. This study adds insights into the synovial heterogeneity in East Asian patients and shows a promising link with predominant inflammatory signals. Evaluating the site of inflammation has the potential to lead to appropriate drug selection that matches the individual pathology.

Metabolomic profiles, polygenic risk scores and risk of rheumatoid arthritis: a population-based cohort study in the UK Biobank

ObjectiveTo investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA).Methods143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants...

Causal effects of time-varying body size on selected autoimmune disorders: a life course Mendelian randomisation study

BackgroundBased on Barker’s hypothesis, some studies investigated the associations between birth weight and several disorders. Apart from issues with statistical power and well-known shortcomings of the observational study design, there...

Association between magnesium, copper, and potassium intakes with risk of rheumatoid arthritis: a cross-sectional study from National Health and Nutrition Examination Survey (NHANES)

BackgroundThe relationship between Mg (magnesium), Cu (copper), and K (potassium) intakes and the risk of rheumatoid arthritis (RA) remains limited. The aim of present study was to examine the associations between Mg, Cu and K intakes with RA.MethodsUsing data from the National Health and Nutrition Examination Survey (NHANES) 2003–2018, we examined the association between Mg, Cu and K intakes and the risk of RA among US adults. After adjustment for age, sex, race, BMI, educational level, smoking history, alcohol consumption, family Poverty Income Ratio (PIR), diabetes and total daily energy intake, logistic regression models and smooth curve fitting were applied to examine the associations of Mg, Cu and K intakes with RA.ResultsA total of 18,338 participants were included (1,008 participants with RA). The multivariate adjusted ORs (95% CI) of RA were [0.66 (0.51, 0.84)], [0.76 (0.60, 0.97)], and [0.75 (0.58, 0.97)] in the highest versus lowest quartile of magnesium intakes, respectively. A nonlinear association between Cu intakes and RA was found. When Cu intake (ln) was between 0.6–2.2 mg, the risk of RA reduced by 26% for every 1 mg increase of intake in Cu [0.74 (0.58, 0.96)].ConclusionsHigher Mg, Cu and K intakes may be inversely associated with the risk of RA among US adults, and an inverse L-shaped association between dietary Cu and RA was found.

Some genetic differences in patients with rheumatoid arthritis

ObjectiveVitamin D is important for bone and cartilage metabolism. Changes in vitamin D blood level may be related to pathological disorders such as rheumatoid arthritis (RA). The main aim of this study is to investigate the association between RA and the vitamin D receptor (VDR) genes FokI and TaqI polymorphisms. One hundred RA patients and fifty healthy matched controls were assessed for VDR FokI and TaqI genotyping. Intact parathyroid hormone (PTH) and calcium (Ca) levels were measured, categorized, and compared between the cases and control groups.ResultsWe found that the FokI genotype frequencies for the RA cases and control groups were FF:Ff:ff = 46%:52%:2% and 50%:50%:0%, respectively (P = 0.76). The TaqI genotype frequencies for the RA cases and control groups were TT:Tt:tt = 45%:44%:11% and 42%:42%:16%, respectively (P = 0.69). A statistically significant high serum PTH level was associated with the ff genotype (p = 0.03), and a significantly low serum Ca level was associated with the TT genotype (p = 0.003). In comparison with controls, no influence of VDR FokI and TaqI genotypes on RA susceptibility or risk was demonstrated.

Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant

TRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using Immunochip data from 3,939 patients with juvenile idiopathic arthritis (JIA) and 14,412 control individuals, we identified 132 plausible common non-coding variants, reduced serially by single-nucleotide polymorphism sequencing (SNP-seq), electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron of TRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-related antigen 2 (FRA2), encoded by FOSL2, resulting in reduced TRAF1 expression and enhanced tumor necrosis factor (TNF) production. Conditioning on this JIA variant eliminated attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding functional variant drives risk of inflammatory arthritis in children and adults.

Menopausal hormone therapy and risk of seropositive rheumatoid arthritis: A nationwide cohort study in Korea

ObjectivesThis retrospective cohort study aimed to investigate the impact of menopausal hormone therapy (MHT) on the incidence of rheumatoid arthritis (RA) in postmenopausal women and to examine the effects of each specific MHT drug. MethodsIn this Korean population-based cohort study, 452,124 women aged > 40 years who consulted a healthcare provider for menopause were evaluated from January 1, 2011, to December 31, 2014. After propensity score matching, 138,991 pairs were included in the MHT and non-MHT groups. Participants were followed up until December 31, 2020. RA was defined according to the International Classification of Diseases, 10th edition, limited to seropositive RA (M05). ResultsRA developed in 567 (0.4 %) of the 138,424 patients in the MHT group. The RA risk in the MHT group was not significantly increased compared with that of controls (hazard ratio [HR] 1.12, 95 % confidence interval [CI] 0.998–1.256). However, MHT use for ≤ 3 years was associated with an increased risk of RA (HR 1.277, 95 % CI 1.127–1.447). When estrogen/progestogen was used, the HR was 1.24 (95 % CI 1.05–1.46), whereas when tibolone was used, the HR was 1.33 (95 % CI 1.13–1.57). ConclusionThe use of MHT did not show a significant impact on the development of RA in postmenopausal women. However, a subanalysis that specifically examined the duration of MHT revealed a noteworthy increase in the risk of RA during the initial 3 years of MHT use.

Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study.

Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset.

Predictive risk factors before the onset of familial rheumatoid arthritis: the Tatarstan cohort study.

A familial history of rheumatoid arthritis (RA) predisposes an individual to develop RA. This study aimed at investigating factors associated with this conversion from the Tatarstan cohort. A total of 144 individuals, referred to as pre-RA and at risk for familial RA, were selected 2 years (range: 2-21 years) before conversion to RA and compared to non-converted 328 first-degree relatives (FDR) from RA as assessed after ≥2 years follow-up, and 355 healthy controls were also selected (HC). Preclinical parameters and socio-demographic/individual/HLA genetic factors were analyzed when data were available at the time of enrollment. As compared to FDR and HC groups, pre-RA individuals were characterized before conversion to RA by the presence of arthralgia, severe morning symptoms, a lower educational level, and rural location. An association with the HLA-DRB1 SE risk factor was also retrieved with symmetrical arthralgia and passive smoking. On the contrary, alcohol consumption and childlessness in women were protective and associated with the HLA-DRB1*07:01 locus. Before RA onset, a combination of individual and genetic factors characterized those who are at risk of progressing to RA among those with familial RA relatives.

The Effect of Physical Activity on Elderly Woman with Rheumatoid Arthritis Symptoms

Rheumatoid Arthritis (RA) is an autoimmune disease that causes joint inflammation. Elderly, especially women are more susceptible to RA due to hormonal factors. RA patient often feel inconvenient during physical activity because of pain in their joint. The purpose of this study was to determine the effect of physical activity on elderly woman with Rheumatoid Arthritis. This research is a literature study using traditional review method. Journal article studies were searched in Google Scholar, OneSearch Indonesia, and Garuda in Bahasa and English language that published online from 2012-2022 according to keywords. Of 9.030 studies from databases identified 30 journal studies were included. Literature studies show that the prevalence of elderly women with RA is higher than men. These studies also shows that severity of RA affects the ability of elderly to do a physical activity and physical activity itself influences reducing pain and preventing the severity of RA. The conclusion of this study is that the prevalence of elderly women with RA is higher than men and physical activity is associated with RA. Suggestions for future researchers to focus more on treatments that can be done to reduce the risk of Rheumatoid Arthritis in elderly.

A Review of Difficult-to-Treat Rheumatoid Arthritis: Definition, Clinical Presentation, and Management.

A subset of patients with rheumatoid arthritis (RA) who fail multiple biologic therapies are deemed to have "difficult-to-treat" (D2T) RA. In 2021, a European Alliance of Associations for Rheumatology (EULAR) task force proposed a clinical definition of D2T RA. Here we review RA phenotypes and clinical assessment of RA, propose a different definition of D2T RA, discuss possible D2T RA risk factors, and summarize existing literature on the management of D2T RA. High disease activity at the time of diagnosis or prior to treatment with a biologic is associated with the development of D2T RA. Prolonged time from diagnosis to beginning treatment has been consistently associated with the development of D2T RA. Other clinical factors such as burden of disease, extraarticular disease, obesity, smoking, pain, fatigue, and psychological conditions have inconsistent associations with D2T RA according to current literature. D2T RA is a relatively new concept that represents an area of great need for research regarding the characterization of those with the disease as well as how best to treat the disease. With this gained knowledge, rheumatologists will be able to better identify patients at the time of diagnosis that are likely to develop D2T RA to help guide management.