Etiology Of Rheumatoid Arthritis Research Articles

The Fidelity of Rheumatoid Arthritis Multivariate Diagnostic Biomarkers Using Discriminant Analysis and Binary Logistic Regression.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that causes multi-articular synovitis. The illness is characterized by worsening inflammatory synovitis, which causes joint swelling and pain. Synovitis erodes articular cartilage and marginal bone, resulting in joint deterioration. This bone injury is expected to be permanent. Cytokines play a prominent role in the etiology of RA and could be useful as early diagnostic biomarkers. This research was carried out at Riyadh's King Khalid University Hospital (KKUH). Patients were enrolled from the Rheumatology unit. Seventy-eight RA patients were recruited (67 (85.9%) females and 11 (14.1%) males). Patients were selected for participation by convenience sampling. Demographic data were collected, and disease activity measurements at 28 joints were recorded using the disease activity score (DAS-28). Age- and sex-matched controls from the general population were included in the study. A panel of 27 cytokines, chemokines, and growth factors was determined in patient and control sera. Binary logistic regression (BLR) and discriminant analysis (DA) were used to analyze the data. We show that multiple cytokine biomarker profiles successfully distinguished RA patients from healthy controls. IL-17, IL-4, and RANTES were among the most predictive variables and were the only biomarkers incorporated into both BLR and DA predictive models for pooled participants (men and women). In the women-only models, the significant cytokines incorporated in the model were IL-4, IL-17, MIP-1b, and RANTES for the BLR model and IL-4, IL-1Ra, GM-CSF, IL-17, and eotaxin for the DA model. The BLR and DA men-only models contained one cytokine each, eotaxin for BLR and platelet-derived growth factor-bb (PDGF-BB) for DA. We show that BLR has a higher fidelity in identifying RA patients than DA. We also found that the use of gender-specific models marginally improves detection fidelity, indicating a possible benefit in clinical diagnosis. More research is needed to determine whether this conclusion will hold true in various and larger patient populations.

Causal inference between rheumatoid arthritis and prostate cancer.

It is unclear if the association between rheumatoid arthritis (RA) and a higher risk of prostate cancer (Pca) reflects a causal relationship. We conducted a meta-analysis and used the Mendelian randomization method (MR) to evaluate the association between RA and Pca risk. A meta-analysis and subgroup analysis of the incidence of Pca in patients with RA was conducted. To determine whether genetically elevated RA levels were causally linked to Pca, two MR samples were employed. To eliminate gender-related bias, we conducted a stratified analysis of the GWAS data for RA by gender, specifically including 140,254 males. Additional MR analysis was also performed to determine potential confounding factors influencing the association between genetically susceptible RA and Pca. In total, 409,950 participants were enrolled in 20 trials to investigate the Pca risk in patients with RA. The meta-analysis suggested that RA was unrelated to the Pca risk (SIR = 1.072, 95% CI, 0.883-1.261). However, a subgroup analysis showed that low smoking rates might increase the Pca risk in patients with RA by 24%. The MR analysis showed that increased genetic susceptibility to RA was related to a high Pca risk (OR = 36.20, 95%CI = 1.24-1053.12, P = 0.037). The causality estimation of MR-Egger, Weighted mode, Simple mode, and Weighted median method were similar in direction and magnitude. Although our meta-analysis found no correlation between RA and Pca risk, MR analyses supported a causal relationship between genetic susceptibility to RA and increased prostate risk. Early attention to Pca risk in patients with RA may be important for improving prognosis and mortality in such patients. Further research is needed to determine the etiology of RA attributed to Pca and its underlying mechanisms.

Appraisal of anti-inflammatory and immunomodulatory potential of ramipril against Freund's adjuvant-provoked arthritic rat model.

Because of evident role ofrenin-angiotensin system in the etiology of rheumatoid arthritis, the current study's objective was to assess the anti-arthritic efficacy of ramipril through CFA-instigated arthritic model. The drug has been shown to have anti-inflammatory potential. CFA-instigated arthritic model assessed the anti-arthritic efficacy of ramipril by estimating different parameters, including paw volume, arthritic index scoring, haematological and biochemical attributes, histological and radiographic analyses, and various cytokines level. Ramipril significantly (p < 0.001) reduced paw volume and the arthritic index especially at the dose of 4mg/kg. The biochemical and haematological changes were likewise restored to normal by ramipril administration with anincrease inanti-inflammatory cytokines while reducing pro-inflammatory cytokines level. Ramipril's ability to prevent arthritis by preserving the normal architecture of arthritis-induced joints is further supported by radiographic and histological investigation. The study's findings demonstrated ramipril's considerable anti-arthritic activity. To identify the precise mechanism of action, however, thorough mechanistic studies are still needed.

Management of cardiovascular disease risk in patients with rheumatoid arthritis

Patients with rheumatoid arthritis along with a risk of developing cardiovascular disease are complex cases for nurses to manage. Louise Murphy details the challenges associated Rheumatoid Arthritis (RA) is a chronic destructive autoimmune disease, characterised by symmetric synovitis. The aetiology of rheumatoid arthritis is complex and largely unknown. Comorbidities such as cardiovascular disease (CVD) are frequently observed in patients with rheumatoid arthritis due to a combination of disease and genetic factors. Cardiovascular disease is one of the leading causes of death in people with rheumatoid arthritis ( Aletaha and Smolen 2018 ) with a 45-60% increased mortality rate due to cardiovascular related events compared to the general population. General practice nurses are in a unique position to be able to provide guidance, advice and support to patients with rheumatoid arthritis who need to make lifestyle changes to reduce CVD risk. General practice nurses can also screen for traditional CVD risk factors and undertake cardiovascular disease risk assessment safely and effectively to identify those patients with rheumatoid arthritis who are at risk of developing cardiovascular disease in the future.

Circadian Regulation of Macrophages and Osteoclasts in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) represents one of the best examples of circadian fluctuations in disease severity. Patients with RA experience stiffness, pain, and swelling in afflicted joints in the early morning, which tends to become milder toward the afternoon. This has been primarily explained by the higher blood levels of pro-inflammatory hormones and cytokines, such as melatonin, TNFα, IL-1, and IL-6, in the early morning than in the afternoon as well as insufficient levels of anti-inflammatory cortisol, which rises later in the morning. Clinical importance of the circadian regulation of RA symptoms has been demonstrated by the effectiveness of time-of-day-dependent delivery of therapeutic agents in chronotherapy. The primary inflammatory site in RA is the synovium, where increased macrophages, T cells, and synovial fibroblasts play central roles by secreting pro-inflammatory cytokines, chemokines, and enzymes to stimulate each other, additional immune cells, and osteoclasts, ultimately leading to cartilage and bone erosion. Among these central players, macrophages have been one of the prime targets for the study of the link between circadian rhythms and inflammatory activities. Gene knockout experiments of various core circadian regulators have established that disruption of any core circadian regulators results in hyper- or hypoactivation of inflammatory responses by macrophages when challenged by lipopolysaccharide and bacteria. Although these stimulations are not directly linked to RA etiology, these findings serve as a foundation for further study by providing proof of principle. On the other hand, circadian regulation of osteoclasts, downstream effectors of macrophages, remain under-explored. Nonetheless, circadian expression of the inducers of osteoclastogenesis, such as TNFα, IL-1, and IL-6, as well as the knockout phenotypes of circadian regulators in osteoclasts suggest the significance of the circadian control of osteoclast activity in the pathogenesis of RA. More detailed mechanistic understanding of the circadian regulation of macrophages and osteoclasts in the afflicted joints could add novel local therapeutic options for RA.

Diagnostic and Predictive Values of IL-6 in a Group of Iraqi Patients with Rheumatoid Arthritis

Background: Researchers have found that interleukin 6 (IL-6) plays a crucial regulatory function in the onset and progression of a wide range of inflammatory disorders. One of the more prevalent inflammatory illnesses affecting people today is rheumatoid arthritis. Aim of the study: The purpose of this study was to compare the IL-6 levels of rheumatoid arthritis (RA) patients to those of healthy controls and to examine the relationship between IL-6 and RA-related demographic and clinical factors. Materials and Method A total of 80 participants: 40 rheumatoid arthritis (RA) sufferers and 40 healthy controls, all of whom ranged in age from 23 to 61. The serum concentrations of (IL-6) were analyzed using an enzyme-linked immunosorbent assay (ELISA). Results: Increased IL-6 blood levels were associated with rheumatoid arthritis, suggesting that this biomarker may be useful for diagnosing the disease at an early stage. There was no statistically significant correlation between disease severity and the DAS28 score and IL-6 levels in the serum. Conclusion: The cytokine interleukin 6 (IL-6) has been proposed as a biomarker and possible player in the etiology of rheumatoid arthritis.

Estimation levels of CTHRC1and some cytokines in Iraqi patients with Rheumatoid Arthritis

Collagen triple helix repeat containing-1 (CTHRC1) is an essential marker for Rheumatoid Arthritis (RA), but its relationship with pro-inflammatory, anti-inflammatory, and inflammatory markers has been scantily covered in extant literature. To evaluate the level of CTHRC1 protein in the sera of 100 RA patients and 25 control and compare levels of tumour necrosis factor alpha (TNF-α), interleukin 10 (IL-10), RA disease activity (DAS28), and inflammatory factors. Higher significant serum levels of CTHRC1 (29.367 ng/ml), TNF-α (63.488 pg/ml), and IL-10 (67.1 pg/ml) were found in patient sera as compared to that in control sera (CTHRC1 = 15.732 ng/ml, TNF-α = 33.788 pg/ml, and IL-10 = 25.122 pg/ml). There was no significant correlation between the level of serum CTHRC1 and DAS28 (r = 0.046, P = 0.650), while there were positive significant correlations between the levels of serum CTHRC1 and CRP (r = 0.372, P = 0.0001), ACPA (r = 0.254, P = 0.01), TNF-α (r = 0.202, P = 0.044), and IL-10 (r = 0.260, P = 0.0001). The level of CTHRC1 (&gt; 25.385 ng/ml) in combination with the levels of CRP and ACPA provided a good indication of RA prediction with sensitivity = 71.0%, specificity = 100.0%, accuracy = 0.71%, positive predictive value (PPV) = 100.0%, and negative predictive value (NPV) = 46.3%. The study showed a significant correlation between the levels of CTHRC1 and TNF-α, and IL-10. These molecules may play a prominent role in the diagnostic and etiology of RA

Polymorphisms in microRNA binding site of SET8 regulate the risk of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex, heterogeneous, progressive and long-term autoimmune disease characterized by symmetrical joint inflammation and bone erosion. The etiology of RA is unclear, but its pathogenesis is associated with oxidative stress and inflammatory cytokines. Single nucleotide polymorphisms (SNPs) in the microRNA (miRNA)-binding sites modify the development of rheumatic disease by regulating the expression of target genes. The present study investigated whether SNPs in the miRNA binding site in the 3' untranslated region (3'-UTR) of SET domain containing (lysine methyltransferase) 8 (SET8) and Keratin 81 (KRT81), namely rs16917496 and rs3660, respectively, were associated with the occurrence of RA. The polymerase chain reaction-ligase detection reaction assay showed that the distribution frequencies of the CC genotype (P=0.025) of SNP rs16917496 in SET8 were significantly higher in patients with RA than in healthy controls, which indicated that the CC genotype was associated with an increased risk of RA. SET8 expression in the blood samples of CC genotype carriers was lower than that of TT genotype carriers. Moreover, the CC genotype carriers exhibited higher reactive oxygen species (ROS) levels (1011.500±536.426 vs. 548.616±190.508, P=0.032) and lower interleukin-10 (IL-10) levels (P<0.001). The present study demonstrated that SNP rs16917496 in the 3'-UTR of SET8 was a predictor of RA risk and may regulate RA development by mediating expression of SET8, thereby regulating the levels of ROS and IL-10.

The Involvement of Glucose and Lipid Metabolism Alteration in Rheumatoid Arthritis and Its Clinical Implication.

Obviously, immune cells like T cells and macrophages play a major role in rheumatoid arthritis (RA). On one hand, the breakdown of immune homeostasis directly induces systemic inflammation; on the other hand, these cells initiate and perpetuate synovitis and tissue damages through the interaction with fibroblast-like synoviocytes (FLS). In recent years, the pathological link between metabolic disorders and immune imbalance has received increasing attention. High energy demand of immune cells leads to the accumulation of metabolic byproducts and inflammatory mediators. They act on various metabolism-sensitive signal pathways as well as relevant transcription factors, such as HIF-1α, and STATs. These molecular events will impact RA-related effectors like circulating immune cells and joint-resident cells in return, allowing the continuous progression of systemic inflammation, arthritic manifestations, and life-threatening complications. In other words, metabolic complications are secondary pathological factors for the progression of RA. Therefore, the status of energy metabolism may be an important indicator to evaluate RA severity, and in-depth explorations of the mechanisms underlying the mystery of how RA-related metabolic disorders develop will provide useful clues to further clarify the etiology of RA, and inspire the discovery of new anti-rheumatic targets. This article reviews the latest research progress on the interactions between immune and metabolism systems in the context of RA. Great importance is attached to the changes in certain pathways controlling both immune and metabolism functions during RA progression.

Deciphering novel common gene signatures for rheumatoid arthritis and systemic lupus erythematosus by integrative analysis of transcriptomic profiles.

Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are the two highly prevalent debilitating and sometimes life-threatening systemic inflammatory autoimmune diseases. The etiology and pathogenesis of RA and SLE are interconnected in several ways, with limited knowledge about the underlying molecular mechanisms. With the motivation to better understand shared biological mechanisms and determine novel therapeutic targets, we explored common molecular disease signatures by performing a meta-analysis of publicly available microarray gene expression datasets of RA and SLE. We performed an integrated, multi-cohort analysis of 1088 transcriptomic profiles from 14 independent studies to identify common gene signatures. We identified sixty-two genes common among RA and SLE, out of which fifty-nine genes (21 upregulated and 38 downregulated) had similar expression profiles in the diseases. However, antagonistic expression profiles were observed for ACVR2A, FAM135A, and MAPRE1 genes. Thirty genes common between RA and SLE were proposed as robust gene signatures, with persistent expression in all the studies and cell types. These gene signatures were found to be involved in innate as well as adaptive immune responses, bone development and growth. In conclusion, our analysis of multicohort and multiple microarray datasets would provide the basis for understanding the common mechanisms of pathogenesis and exploring these gene signatures for their diagnostic and therapeutic potential.

Vitamin D status and risk of rheumatoid arthritis: systematic review and meta-analysis

BackgroundVitamin D is important for immunomodulation and may play a role in autoimmune diseases. Studies have reported a high prevalence of vitamin D deficiency in rheumatoid arthritis (RA) patients, and vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D] concentration, is inversely associated with RA disease activity. However, it is unclear whether vitamin D deficiency increases the risk of later developing RA. We conducted a systematic review and meta-analysis of pre-diagnostic 25(OH)D concentrations and risk of RA.MethodsMedline and Embase databases were searched in December 2021 using various keywords for ‘vitamin D’, ‘rheumatoid arthritis’, and ‘prospective study’. Publications identified from the search were screened for eligibility, studies were excluded if vitamin D status was measured at or after RA diagnosis, and data were extracted from relevant articles. Bayesian meta-analysis was used to estimate the summary relative risk (RR) and 95% credible interval (CrI) for risk of RA in relation to circulating 25(OH)D concentrations, as well as the between-study heterogeneity.ResultsThe search strategy yielded 908 records, of which 4 publications reporting on 7 studies, involving a total of 15,604 participants and 1049 incident RA cases, were included in the meta-analysis. There was no suggestion of an association between 25(OH)D concentration and subsequent risk of RA. The pooled RR per 25 nmol/L increment in 25(OH)D was 0.96 (95% CrI 0.82–1.13; I2 = 52%). No associations were evident in men (RR = 1.02, 95% CrI 0.65–1.61; I2 = 77%, 2 studies) or women (RR = 0.94, 95% CrI 0.73–1.22; I2 = 71%, 4 studies).ConclusionsThis systematic review and meta-analysis did not identify evidence of an association between 25(OH)D and RA risk, but there was notable between-study heterogeneity and a lack of precision. Investigations in large-scale prospective studies with long follow-up or suitably designed Mendelian randomisation studies with consideration of potential non-linear relationships are needed to determine whether vitamin D is involved in RA aetiology.

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis.

In recent years, diagnostic and therapeutic approaches for rheumatoid arthritis (RA) have continued to improve. However, in the advanced stages of the disease, patients are unable to achieve long-term clinical remission and often suffer from systemic multi-organ damage and severe complications. Patients with RA usually have no overt clinical manifestations in the early stages, and by the time a definitive diagnosis is made, the disease is already at an advanced stage. RA is diagnosed clinically and with laboratory tests, including the blood markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the autoantibodies rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). However, the presence of RF and ACPA autoantibodies is associated with aggravated disease, joint damage, and increased mortality, and these autoantibodies have low specificity and sensitivity. The etiology of RA is unknown, with the pathogenesis involving multiple factors and clinical heterogeneity. The early diagnosis, subtype classification, and prognosis of RA remain challenging, and studies to develop minimally invasive or non-invasive biomarkers in the form of biofluid biopsies are becoming more common. Non-coding RNA (ncRNA) molecules are composed of long non-coding RNAs, small nucleolar RNAs, microRNAs, and circular RNAs, which play an essential role in disease onset and progression and can be used in the early diagnosis and prognosis of RA. In this review of the diagnostic and prognostic approaches to RA disease, we provide an overview of the current knowledge on the subject, focusing on recent advances in mRNA-ncRNA as diagnostic and prognostic biomarkers from the biofluid to the tissue level.

AN EVALUATION OF DIETARY APPROACHES USED IN THE CLINICAL MANAGEMENT OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation, persistent synovitis, and other comorbidities, that affects 0.5-1.0% of the overall population. Long-term active RA causes severe joint damage, disabling pain and diminished life quality. The etiology of RA is not accurately understood, but it is thought to be due to an interaction between the responses of the innate and acquired immune systems. RA is characterized by the presence of Rheumatoid Factor (RF) and anti citrullinated peptide antibodies in the blood circulation. Also the composition of intestinal the gut microbiome is claimed to be critical in immune responses associated with RA. Changes in the microbiota are thought to be related to the risk and severity of the disease. Three regions; primarily the lungs, oral mucosa and gastrointestinal tract have been associated with changes in the microbiota. Commonly, the pharmaceutical treatment of RA includes non-steroidal anti-inflammatory drugs (NSAIDs) that are used to manage the pain and inflammation associated with RA and disease-modifying anti-rheumatic drugs that reduces pain by slowing down the disease. Unfortunately, remission is not likely in many patients. Moreover, side effects related to drugs are commonly reported. Some alterations in the patients’ life and environment are thought to aggravate symptoms, thus influencing severity of RA. For example RA patients, the participants asserted that consumption of red meat, alcoholic and non-alcoholic beverages worsen their symptoms, while nutrients such as fish and blueberries help alleviate the symptoms. To manage the adverse effects of RA, particular dietary alterations are suggested to be effective in reducing inflammation, increasing antioxidant levels, and improving lipid profiles. Antigenic load and food intolerance are thought to play a role in both the onset of Rheumatoid Arthritis. Besides, it has been shown that the intestinal mucosa of the patients would have become more permeable to allergens due to long term NSAIDs use. In this sense, Elimination Diet, Mediterranean Diet, Vegan/Vegetarian Diet approach, Omega-3 Fatty acids, Vitamin D and probiotic supplementation is thought to reduce disease activity. The purpose of this review is to evaluate the efficiency of certain dietary approaches and supplements used for lessening the RA related symptoms, based on the scientific evidence found in the literature.

Arthritis and Planning Conception

Arthritis is a form of joint disorder characterized by chronic inflammation in one or more joints that usually results in pain and is often disabling. Rheumatoid arthritis (RA) is a chronic, systemic, debilitating, chronic inflammatory autoimmune disease of synovial joints, which can lead to chronic pain and structural joint damage, as well as other organ involvement, especially if not adequately controlled. The etiology of RA is still unknown. Patients with rheumatoid arthritis have special family planning considerations that require a frank discussion and careful coordination with health care providers. More than 2/3rdof patients experience improvement or even remission of arthritis during gestation. The improvement in RA symptoms can be seen both with changing the eating pattern as well as with inclusion and exclusion of certain food items in the diet.

Research Progress of Chinese and Western Medicine in Treatment of Rheumatoid Arthritis

At present, the etiology of rheumatoid arthritis (RA) is not clear, and its pathogenesis has not been clarified. For this, in clinic can only make corresponding treatment for the onset period and sequelae of the disease. Through reviewing relevant literature in recent years, it is found that the combined use of traditional Chinese and western medicine has great advantages in the treatment of rheumatoid arthritis. This paper will analyze and summarize the current treatment status and medication rules of traditional Chinese and western medicine for rheumatoid arthritis, hoping to provide reference for clinical treatment plans, so as to further improve clinical efficacy and improve treatment plans.

Anticitrullinated antibodies recognize rheumatoid arthritis associated T-cell epitopes modified by bacterial L-asparaginase.

Citrullinated proteins and anti-citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). It has been suggested that during inflammation or dysbiosis, bacteria could initiate production of ACPAs. Most patients with RA are seropositive for ACPAs, but these antibodies have overlapping reactivity to different posttranslational modifications (PTMs). For initiation and development of RA, T lymphocytes and T cell epitopes are still required. In this study, we evaluated the ability of bacterial L-asparaginase to modify RA-related T cell epitopes within type II collagen (CII259-273 and CII311-325), as well as whether these modified epitopes are recognized by ACPAs from RA patients. We included 12 patients with early RA and 11 healthy subjects selected according to predefined specific criteria. LC-MS/MS analyses revealed that the bacterial L-asparaginase can modify investigated T cell epitopes. ELISA tests showed cross-reactivity of ACPA positive sera from early RA patients towards the enzymatically modified immunodominant T cell epitopes within type II collagen (CII), but not to the modified irrelevant peptides. These data suggest that the cross-reactive ACPAs recognize the "carbonyl-Gly-Pro" motif in CII. Moreover, the T cell recognition of the modified major immunodominant T cell epitope Gal264-CII259-273 was not affected. This epitope was still able to activate autoreactive T cells from early RA patients. It is likely that such modifications are the missing link between the T cell priming and the development of anti-modified protein antibodies (AMPAs). Our results provide additional information on the etiology and pathogenesis of RA.

Interleukin-34-regulated T-cell responses in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a multifaceted etiology, which primarily affects and results in the deterioration of the synovium of patients. While the exact etiology of RA is still largely unknown, there is growing interest in the cytokine interleukin-34 (IL-34) as a driver or modulator of RA pathogenesis on the grounds that IL-34 is drastically increased in the serum and synovium of RA patients. Several studies have so far revealed the relationship between IL-34 levels and RA disease progression. Nevertheless, the significance and role of IL-34 in RA have remained ambiguous, as illustrated by two most recent studies, which reported contrasting effects of genetic IL-34 deletion in RA. Of note, IL-34 is a macrophage growth factor and is increasingly perceived as a master regulator of T-cell responses in RA via macrophage-dependent as well as T cell-intrinsic mechanisms. In this regard, several studies have demonstrated that IL-34 potentiates helper T-cell (Th) responses in RA, whereas studies also suggested that IL-34 alleviates synovial inflammation, potentially by inducing regulatory T-cells (Treg). Herein, we provide an overview of the current understanding of IL-34 involvement in RA and outline IL-34-mediated mechanisms in regulating T-cell responses in RA.

Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10-8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.

Serum Interleukin-17 and its Correlation with Anti-CCP antibodies, Vitamin D3, and Obesity in Rheumatoid Arthritis women Patients

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Members of the IL-17 cytokine family have various biological functions, including enhancing defense against multiple pathogens while promoting inflammatory pathology during autoimmune disease. Additionally, it has been suggested that vitamin D may be connected to the etiology of RA. Therefore, this study aimed to assess serum IL-17 and vitamin D3 concentrations in RA women and determine how these levels relate to anti-CCP, obesity, and age.Methods: This work included eighty women aged between (22-60) years. Sixty were afflicted with RA and attended the department of rheumatology and medical rehabilitation centre for rheumatic diseases at Rzgary teaching hospital-Erbil, Iraq, compared to twenty healthy women. The concentrations of Anti-CCP antibodies as a diagnostic test, Vitamin D3 and IL-17, were assessed by ELISA. The Mann-Whitney U test and normality were applied for the statistical analysis of the results. Also, the relationship between the study parameters was examined using Pearson's correlation. The ideal cutoff value for IL-17 with the highest sensitivity and specificity was detected using a Receiver Operating Characteristic (ROC) Curve. Results: This study revealed that serum IL-17 levels were significantly higher in RA women than in the control group (p &lt; 0.001) and that serum VD3 levels were significantly lower in RA women than in healthy controls. Seropositive anti-CCP Ab was found in about 42% of RA patients. The pro-inflammatory IL-17 serum level was positively correlated with vitamin D, age, and obesity in RA women. The best IL-17 cutoff for predicting the presence of RA was 69.5 pg/ML, with a sensitivity of 96% and a specificity of 75%. Conclusion: In patients with RA, vitamin D deficiency was common and correlated with age. Consequently, a high level of suspicion is needed when assessing at-risk patients, particularly women who complain of vitamin D deficiency.

Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and cartilage/bone destruction with systemic comorbidities. Despite advances in understanding the aetiology of RA and novel biologic drugs, a substantial number of individuals with RA remain intolerant or resistant to these therapies. In this context, mesenchymal stem/stromal cell (MSC)-based therapy has emerged as an innovative therapeutic alternative to address unresolved treatment issues for patients with RA thanks to the immunomodulatory properties of these cells. The majority of preclinical studies in MSC-based therapy have been conducted using the well-known collagen-induced arthritis (CIA) mouse model however due to its low incidence, the mouse strain restriction and the prolonged induction phase of collagen-induced arthritis, alternative experimental models of RA have been developed such as K/BxN serum transfer-induced arthritis (STIA), which mimics many of human RA features. In this study, we evaluate whether the K/BxN STIA model could be used as an alternative model to study the immunomodulatory potential of MSC-based therapy. Unexpectedly, our data suggest that adipose-derived MSC-based therapy is unsuitable for modulating the progression of K/BxN serum-transfer arthritis in mice despite the various experimental parameters tested. Based on the differences in the immune status and monocytic/macrophage balance among the different arthritic models, these results could help to identify the cellular targets of the MSCs and, most importantly to predict the RA patients that will respond positively to MSC-based therapy.