Markers Of Rheumatoid Arthritis Research Articles

FCER1G Gene Hypomethylation in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that, when improperly treated, leads to disability in patients. Various factors that may cause the development and activity of RA are being considered. Epigenetic factors are also receiving increasing attention. In our study, we analyzed the association between FCER1G gene methylation and RA activity. We conducted our study in 50 RA patients and 24 controls. The patients were divided into two groups in terms of high disease activity and remission. Quantitative real-time methylation-specific PCR was used to analyze the methylation status of the investigated genes. We observed that RA patients have lower levels of methylation of the FCER1G gene compared to controls, but we did not find any difference in the methylation status of this gene between patients with high disease activity and remission. The results of this study suggest that FCER1G gene methylation may be a new potential epigenetic marker of RA that is independent of disease activity.

The Effect of Inhaled Air Particulate Matter SRM 1648a on the Development of Mild Collagen-Induced Arthritis in DBA/J Mice

Air pollution is considered to be one of a risk factor for rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is commonly used as a mouse model of human RA. However, the impact of specific particulate matter (PM) components on the incidence and severity of RA has still not been established. The aim of this study was to develop an experimental model of CIA suitable to test arthritogenicity of inhaled PM. A mild form of CIA was induced in DBA1/J mice inhaled with various components of SRM 1648a PM. The incidence and severity of arthritis was assessed, and the selected serum markers of autoimmunity and inflammation were determined. Clinical arthritis was observed from the booster CII immunisation onward. Anti-cyclic citrullinated peptide antibodies, a diagnostic marker of RA, were detected in serum of these mice. All inhaled pollutants, crude PM, PM with reduced organic content, ferric, and silica nanoparticles markedly increased CIA incidence and severity. The fastest progression of CIA development was caused by crude PM and was linked to enhanced serum levels of anti-CII IgG, the prominent arthritogenic autoantibodies. On the other hand, inhaled nanoparticles enhanced serum levels of TNFα, a major proinflammatory arthritogenic cytokine. We recommend this experimental model of mild CIA to test the mechanisms of arthritis exacerbation by inhaled air pollutants. Further studies are necessary to determine whether PM-aggravated arthritis is caused by inflammatory mediators translocated from inflamed lung into systemic circulation or whether PM translocated into the bloodstream directly exacerbate joint inflammation.

Three key genes expression profiling in Egyptian rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a multi-system autoimmune disease with synovial joints involvement. The triad of autoimmunity, genetics, and environment is the key player in RA pathogenesis. We intended to investigate gene expression of C-C Chemokine Ligand 2 (CCL2), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in RA patients versus controls, and its correlation with the activity of the disease. The relative expression of PTPN22, CTLA-4, and CCL2 in the peripheral blood of 59 RA patients and 50 controls was determined using RT-PCR. There was a significantly higher median (inter-quartile range) expression of CTLA-4 and CCL2 in RA patients in comparison to controls (P < 0.05). However, in RA patients, PTPN22 expression was significantly lower than in controls (P=0.0001). A weak significant correlation was detected between PTPN22 and either CTLA-4 or CCL2. Also, on comparing RA patients with moderate to severe disease activity versus those who have a mild disease activity, CCL2 was significantly over-expressed (P > 0.05). Thus, in Egyptian RA patients, there was a significant PTPN22 down-expression and greater expression of CTLA-4 and CCL2. Moreover, over-expression of CCL2 in RA patients with moderate-to-severe disease activity was significant. We conclude that these three key genes could become useful diagnostic markers for RA and CCL2 expression as a good prognostic tool for RA disease activity.

Identification of Critical Biomarkers and Immune Infiltration in Rheumatoid Arthritis Based on WGCNA and LASSO Algorithm.

Rheumatoid arthritis(RA) is the most common inflammatory arthritis, and a significant cause of morbidity and mortality. RA patients’ synovial inflammation contains a variety of genes and signalling pathways that are poorly understood. It was the goal of this research to discover the major biomarkers related to the course of RA and how they connect to immune cell infiltration. The Gene Expression Omnibus was used to download gene microarray data. Differential expression analysis, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO) regression were used to identify hub markers for RA. Single-sample GSEA was used to examine the infiltration levels of 28 immune cells and their connection to hub gene markers. The hub genes’ expression in RA-HFLS and HFLS cells was verified by RT-PCR. The CCK-8 assay was applied to determine the roles of hub genes in RA. In this study, we identified 21 differentially expressed genes (DEGs) in RA. WGCNA yielded two co-expression modules, one of which exhibited the strongest connection with RA. Using a combination of differential genes, a total of 6 intersecting genes was discovered. Six hub genes were identified as possible biomarkers for RA after a lasso analysis was performed on the data. Three hub genes, CKS2, CSTA, and LY96, were found to have high diagnostic value using ROC curve analysis. They were shown to be closely related to the concentrations of several immune cells. RT-PCR confirmed that the expressions of CKS2, CSTA and LY96 were distinctly upregulated in RA‐HFLS cells compared with HFLS cells. More importantly, knockdown of CKS2 suppressed the proliferation of RA‐HFLS cells. Overall, to help diagnose and treat RA, it’s expected that CKS2, CSTA, and LY96 will be available, and the aforementioned infiltration of immune cells may have a significant impact on the onset and progression of the disease.

CKS2 and S100A12: Two Novel Diagnostic Biomarkers for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systematicness autoimmunity disease with joint inflammation. RA etiology is still unknown. Early and exact diagnosing is still hard to reach. In the paper, we purposed to discover novel diagnosis biological marker for RA. Two open, usable gene expression profiles of human RA as well as controlled specimens (dataset GSE17755 as well as GSE93272) were downloaded from the GEO database. Differentially expressed genes (DEGs) were screened between 331 RA and 88 control samples. Functional enrichment analysis was applied to explore the possible function of DEGs. Expression levels as well as diagnosis values of biological marker in RA were further verified in our cohort by the use of RT-PCR and ROC assays. We identified 13 DEGs between RA samples and control samples. 13 DEGs were remarkably abundant in NF-kappa B signal pathway. Among the 13 DEGs, CKS2, S100A12, LY96, and ANXA3 exhibited a strong diagnostic ability in screening RA specimens from normal specimens using all AUC > 0.8. Moreover, we confirmed that the expression of CKS2 and S100A12 was distinctly upregulated in RA specimens contrasted to normal specimens. Overall, serum CKS2 and S100A12 could be used as novel diagnosis biological markers for RA patients.

Interrelationship of Metabolic Syndrome and Rheumatoid Arthritis in North Indian Population

Objective: The metabolic syndrome (MetS) may be responsible for occurrence of high frequency of cardiovascular disease in rheumatoid arthritis (RA) patients. An association between inflammatory activity of RA and MetS has also been speculated. This study was designed to see whether presence of MetS along with RA increases the severity of disease and to find the risk association of the disease severity markers of RA namely TNF-α, anti-CCP, RF, CRP and ESR with MetS. Methodology: 185 patients of RA (EULAR 2010) were recruited and assessed for MetS according to NCEP/ATP III criteria. Serum level of disease specific biomarkers of RA namely TNF-α, anti-CCP, RF, CRP and ESR were quantified in all patients and compared between RA with MetS and only RA patients. Cytokine TNF-α, anti-CCP, RF, and CRP were assayed through ELISA. Results: The prevalence of MetS among RA patients was 41.2%. The mean age of RA cases with MetS is significantly older (55.65yrs) with increased disease duration. The levels of TNF-α, anti-CCP, CRP and ESR along with EULAR &amp; DAS score were significantly (p&lt;0.05) high in RA with MetS. TNF-α showed maximum risk (OR=6.3; p=0.03) in development of MetS. Longer disease duration with high anti-CCP, CRP and DAS-28 were also contributing significantly in MetS development. Conclusion: A positive vicious cycle is working between the pathogenesis of RA and MetS through inflammatory cytokines and biomarkers. MetS in RA is associated with increased disease severity. Keywords: Rheumatoid arthritis, Metabolic syndrome, Biomarkers, Cytokine TNF-α, Disease severity

CLP1 is a Prognosis-Related Biomarker and Correlates With Immune Infiltrates in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease with a high disability rate that seriously affects society and individuals. However, there is a lack of effective and reliable diagnostic markers and therapeutic targets. In this study, we identified diagnostic markers of RA based on RNA modification and explored its role as well as degree of immune cell infiltration. We used the gene expression profile data of three synovial tissues (GSE55235, GSE55457, GSE77298) from the Gene Expression Omnibus (GEO) database and the gene of 5 RNA modification genes (including m6A, m1A, m5C, APA, A-1), combined with cluster analysis, identified four RNA modifiers closely related to RA (YTHDC1, LRPPRC, NOP2, and CLP1) and five immune cells namely T cell CD8, CD4 memory resting, T cells regulatory (Tregs) Macrophages M0, and Neutrophils. Based on the LASSO regression algorithm, hub genes and immune cell prediction models were established respectively in RA and a nomogram based on the immune cell model was built. Around 4 key RNA modification regulator genes, miRNA-mRNA, mRNA-TF networks have been established, and GSEA-GO, KEGG-GSEA enrichment analysis has been carried out. Finally, CLP1 was established as an effective RA diagnostic marker, and was highly positively correlated with T cells follicular helper (Tfh) infiltration. On the other hand, highly negatively correlated with the expression of mast cells. In short, CLP1 may play a non-negligible role in the onset and development of RA by altering immune cell infiltration, and it is predicted to represent a novel target for RA clinical diagnosis and therapy.

C-reactive protein as a disease activity marker in rheumatoid arthritis

Introduction: CRP is a valuable marker and regulator of systemic inflammation in RA that also appears to play a direct role in bone destruction and radiographic progression. CRP has also been implicated in the etiology of common comorbidities associated with RA. Decreasing CRP levels with RA treatment may contribute to reductions in disease activity, although beneficial effects of RA treatment seem to occur irrespective of CRP values. Aim: The purpose of this study was to examine whether levels of C-reactive protein (CRP), a sensitive marker of disease activity in rheumatoid arthritis (RA). Materials &amp; methods: This study was carried out on 39 RF Positive patients from both sexes male and female from different age group at NIMS Super-Specialty Hospital, Sobha Nagar, Jaipur, Rajasthan. Inflammatory markers were performed in the laboratory. Results: In the current study, the majority of Rheumatoid Arthritis patients belong to the age group of 41 to 60 (58.97%) and male to female ration were 1:2. C - reactive protein found highly significant positive correlation. Out of total Rheumatoid Arthritis patients, 7.69% patients have normal C - reactive protein level and 92.30% have highly increased CRP level. T

Proteome Profiling Identifies Serum Biomarkers in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein–protein interaction (PPI) network topological analysis methods. Markers were reanalyzed using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, and diagnostic receiver-operating characteristic analysis. We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8+T cell, and natural killer cell in the pathological mechanism, which can be better utilized for future research on RA. This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.

Adiponectin: A novel prognostic marker for rheumatoid arthritis: A case control study in a tertiary care hospital in central India

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by symmetrical synovitis, progressive damage to the articular cartilage and the subchondral bone, pain, fatigue, and disabilityRecognition of RA as early as possible is important, because a significant proportion of the patients develop irreversible joint damage shortly after disease onset &amp; risks associated with its treatment. The adiponectin is an active participant in the regulation of physiological and pathological processes, inflammatory process as mediator. This study was done to compare the progression of rheumatoid arthritis in conjunction with changes in levels of adiponectin and to evaluate its role as a prognostic marker. Analyse serum adiponectin level to evaluate its potential role to assess disease severity in patients of rheumatoid arthritis &amp; compare its level in normal healthy control subjects. This study was conducted in MY Hospital, Indore. We enrolled 50 cases of confirmed rheumatoid arthritis patients of 20-70 years age group and 50 age and sex matched apparently healthy controls. Both cases (n=50) and controls (n=50) were assessed for haematological tests and biochemical tests, lipid profile, uric acid, CRP &amp; adiponectin. The data were expressed as mean ± SD and analysed by using SPSS version 20. P-value of &amp;#60; 0.05 was accepted as statistically significant. The mean age of the cases was 44.74 ± 13.10 and that of controls was 42.26 ± 8.09. Maximum number of study patients were in the age group of 31-40 years &amp; women. The rheumatoid arthritis group was divided into subgroup according to DAS28 Score. Out of 50 cases, 2 patients (4.0%) had remission, 2 patients (4.0%) had low disease activity, 30 patients (60.0%) had moderate disease activity and 16 patients(32.0%) had high disease activity. The mean CRP in the rheumatoid arthritis group was 21.56 ± 25.46 mg/dL while in the control group was 11.09 ± 7.95 mg/L. The difference was found to be statistically significant (p&amp;#60;0.05).The mean ESR in the rheumatoid arthritis group was 21.26 ± 8.88 mm/hour while in the control group was 15.70 ± 5.40 mm/hour. The difference was found to be statistically significant (p&amp;#60;0.05).The mean adiponectin level in the rheumatoid arthritis group was 30.13 ± 13.04 µg/ml while in the control group was 17.08 ± 8.69 µg/ml. The difference was found to be statistically significant (p&amp;#60;0.05).The mean adiponectin level was highest in the high disease activity subgroup and lowest in the low disease activity subgroup.In our study we concluded that patients of rheumatoid arthritis have raised level of adiponectin &amp; CRP as compared to normal healthy control group. Adiponectin might be better marker for RA compare to CRP &amp; ESR. Also higher levels of adiponectin were observed in patients with severe disease. Therefore, adiponectin might be used for screening which will help in predicting disease progression.

Electrochemical immunodetermination of connective tissue growth factor levels on nitrogen-doped graphene.

Connective tissue growth factor (CTGF) is a disease marker of rheumatoid arthritis (RA), and its rapid and sensitive detection is essential for the diagnosis of RA. In this work, a three-dimensional pore structure of alkali-activated nitrogen-doped graphene (aN-G) was used as an electrode modification material, and a label-free electrochemical immunosensor for the sensitive detection of CTGF was successfully constructed by the formation of an amide bond between amino groups in protein and carboxyl groups on the carbon surface. Under optimized conditions, the sensor achieved accurate detection of CTGF in the wide range of 0.0625 ~ 2000pgmL-1. It had good accuracy (95.0 ~ 100.1%), repeatability (1.2 ~ 2.2%), stability, selectivity, and a low limit of detection (0.0424pgmL-1, S/N = 3). The sensor was used in serum samples of patients with RA, and CTGF was also successfully detected. Based on this, the electrochemical sensor is expected to become an effective method for RA diagnosis and treatment effect evaluation.

Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis.

Aims This study is aimed at investigating the pathogenesis of rheumatoid arthritis (RA) by identifying key biomarkers, associated immune infiltration, and small-molecule compounds using bioinformatic analysis. Methods Six datasets were obtained from the Gene Expression Omnibus database, and the batch effect was adjusted. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyse differentially expressed genes (DEGs). Furthermore, candidate small-molecule drugs associated with RA were selected from the Connectivity Map (CMap) database. The least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and multivariate logistic regression analyses were performed on DEGs to screen for RA diagnostic markers. The receiver operating characteristic curve, concordance index, and GiViTi calibration band were the metrics used to assess the diagnostic markers of RA identified in this analysis. The single-sample gene set enrichment analysis was performed to calculate the scores of infiltrating immune cells and evaluate the activities of immune-related pathways. Finally, the correlation between screening markers and RA diagnosis was determined. Results A total of 227 DEGs were identified. Functional enrichment analysis and KEGG revealed that DEGs were enriched by the immune response. CMap analysis identified 11 small-molecule compounds with therapeutic potential for RA. In gene expression, the activities of 13 immune cells and 12 immune-related pathways significantly differed between patients with RA and healthy controls. DPYSL3 and SPP1 had the potential to diagnose RA. SPP1 expression was positively correlated with DPYSL3 in 11 immune cells and 10 immune-related pathways. Conclusion This study comprehensively analysed DEGs and immune infiltration and screened for potential diagnostic markers and small-molecule compounds of RA.

Efficacy and drug retention of tofacitinib in rheumatoid arthritis: from the nationwide Korean College of Rheumatology Biologics registry.

Janus kinase inhibitors are expected to change the management patterns and prognosis of chronic rheumatic diseases. This study aimed to evaluate the efficacy, drug retention, and adverse events of tofacitinib, a Janus kinase inhibitor, for rheumatoid arthritis (RA) using a Korean nationwide database. Data of patients with RA receiving tofacitinib were extracted from the Korean College of Rheumatology Biologics and Targeted Therapy registry, including clinical characteristics and disease activity markers for RA. Outcomes of clinical efficacy, drug survival rate, and safety profiles were compared between biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and -failure patients. Mann-Whitney U-test, logistic regression analysis, Kaplan-Meier analysis, and log-rank test were used in data analysis. Three hundred patients with RA received tofacitinib therapy (16.3% male; mean age 55.4±11.9 years); 91 patients were bDMARD-naive. Baseline disease activity markers and proportions of patients who were taking conventional synthetic DMARDs were not different between bDMARD-naive and bDMARD-failure patients. American College of Rheumatology responses and disease activity score-28 did not differ between bDMARD-failure and -naive patients at the 1-year follow-up. The drug retention rate of tofacitinib did not differ between bDMARD-failure (155 per 2.4 years) and -naive patients (89 per 1.9 years) (log-rank test, p=0.202). In logistic regression, the positivity of RF and ACPA were associated with reduced drug retention (p=0.01 and 0.02, respectively). Totally 83 (27.7%) of patients had adverse, and 14 (4.7%) patients had herpes zoster infection. Nationwide real-world data showed that tofacitinib therapy is effective in patients with RA independent of previous use of a bDMARD. The drug retention of tofacitinib did not differ between bDMARD-failure and -naive patients, and RF or ACPA positivity may be associated with reduced discontinuation of tofacitinib.

Role of biochemical markers in rheumatoid arthritis

Rheumatoid arthritis is the most common chronic, progressive systemic inflammatory arthritis of unknown cause. It affects approximately 1-2% of the population worldwide. It is a form of autoimmune disease principally synovial tissues. As the pathophysiology involves affecting cell mediated immune response, adenosine deaminase may have a role in rheumatoid arthritis. As it involves bones and joints, it is likely that it alters the levels of Serum Calcium, Phosphorus and Magnesium as well as Alkaline Phosphatase which may be helpful in diagnosis or management of the disease. 1. To evaluate the role of serum adenosine deaminase (ADA) as a marker of cell mediated immunity in Rheumatoid Arthritis. 2. To estimate serum alkaline phosphatase, calcium, phosphorus and magnesium as prognostic markers of Rheumatoid arthritisA cross-sectional, case control study with convenient sampling was undertaken after Institutional Ethical Clearance &amp; informed consent. 30 patients of Rheumatoid Arthritis presenting to the orthopaedic outpatient department of Owaisi Hospital and Research Centre, Hyderabad were taken as cases along with an equal number of age and sex matched controls from January 2021 to June 2021. ADA levels were estimated by colorimetric assay on ErbaChem 7 semiautoanalyser. Serum Alkaline phosphatase, Calcium, Phosphorus and Magnesium were estimated on Cobas C311 autoanalyzer. There was a significant increase in levels of Adenosine Deaminase, Alkaline Phosphatase and Serum Phosphorus, while the levels of Calcium and Magnesium were significantly reduced in rheumatoid arthritisADA as a marker of cell mediated immunity reflects monocyte / macrophage activity and was increased in our study suggesting immunological and inflammatory process in the pathogenesis of Rheumatoid Arthritis (R.A). It can be used as a non invasive marker of chronic inflammation and may provide additional information about disease prognosis.Increased levels of Alkaline Phosphatase and Phosphorus associated with low Calcium and Magnesium suggest increased bone resorption in R. A and are useful as markers of disease activity.

The Role of Different Circulating T Follicular Helper Cell Markers in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic incurable inflammatory autoimmune disease. T follicular helper (Tfh) cells expressing different markers play critical roles in the development of RA. However, their specific mechanisms of action and association with RA clinical parameters are not clear. We therefore performed a cohort study to investigate the effects of different Tfh cell markers on RA pathogenesis. We retrospectively reviewed clinical data from 30 patients diagnosed with RA and 30 healthy controls (HCs) who visited our hospital. Based on X-ray findings, the patients were divided into a joint bone erosion group (n = 17) and a non-erosive joint bone group (n = 13). Using flow cytometry, we determined the frequencies of five peripheral blood CD4+ Tfh cell types characterized by different markers, and examined these cell types for correlations with clinical parameters. RA patients exhibited higher frequencies of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+OX40+, and CD4+CXCR5+CD40L+ Tfh cells than HCs. CD4+CXCR5+, CD4+CXCR5+CD40L+, and CD4+CXCR5+OX40+ Tfh cell frequencies positively correlated with disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR), while those of CD4+CXCR5+ and CD4+CXCR5+CD40L+ Tfh cells were related to rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies. In RA patients without joint bone erosion, CD4+CXCR5+CD40L+ Tfh cell frequencies were positively correlated with both RF and DAS28-ESR. Serum anti-CCP antibody levels and CD4+CXCR5+ICOS+ Tfh cell frequencies were also positively correlated. Circulating CD4+CXCR5+CD40L+ Tfh cells appear to play critical roles in RA pathogenesis, and restricting CD4+CXCR5+CD40L+ Tfh cells may be a therapeutic strategy for controlling RA.

Delicate regulation of IL-1β-mediated inflammation by cyclophilin A.

The inflammatory response is tightly regulated, but its regulatory principles are still incompletely understood. Cyclophilin A (CypA) has long been considered as a pro-inflammatory factor. Here, we discover how CypA precisely regulates interleukin-1β (IL-1β)-mediated inflammatory responses. In lipopolysaccharide-treated mice, CypA deficiency initially inhibits and then promotes lung inflammation, which is closely related to IL-1β production. Mechanistically, CypA not only facilitates pro-IL-1β processing by increasing Smurf1-mediated K63-linked ubiquitination in an ATP-dependent manner but also accelerates pro-IL-1β degradation, depending on Smurf1-mediated K48-linked ubiquitination. Moreover, in IL-1β-treated mice, CypA exacerbates lung injury by enhancing cytokine production. It also upregulates the ILK/AKT pathway by inhibiting Cyld-mediated K63-linked ILK deubiquitination, which promotes the epithelial-mesenchymal transition (EMT) to facilitate lung repair. Collectively, CypA promotes inflammation activation by increasing IL-1β production and then promotes inflammation resolution by enhancing redundant pro-IL-1β degradation and IL-1β-induced EMT, indicating the complex and delicate regulation of inflammatory response.

Epicardial Fat Thickness: A Cardiometabolic Risk Marker in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology which mainly involves synovial joints. However, the corresponding systemic inflammation may result in disorders of multiple other organ systems. Several organs and organ systems are potentially involved in RA, particularly in severe diseases. The organs most involved are the lung, heart, eyes, and nervous system. Extra-articular manifestations of RA may develop even before the onset of arthritis. Emerging epidemiological evidence shows that cardiovascular disease (CVD) accounts for near about 50% of RA-associated death. Epicardial fat thickness (EFT) has recently emerged as a new marker of cardiometabolic risk. Although Epicardial fat (EF) is needed for heart muscle function, given its intrinsic inflammatory status, EFT displays the potential to serve as a therapeutic target in patients with RA.Objectives: To evaluate EFT using echocardiography in RA patients compared to age and sex-matched control and to find the factors associated with EFT in RA patients.Materials and methods: This current study was conducted in the Department of Medicine, Postgraduate Institute of Medical Education & Research. The study was conducted from November 2016 to March 2018. Patients with BMI ≥ 30 kg/m2, diabetes mellitus, primary hyperlipidemia, and uncontrolled hypertension were particularly excluded. Thirty patients of age and sex-matched controls were also taken for the study. All the patients and controls selected for the study were subjected to detailed history taking and clinical examination. They were subjected to lab investigations and echocardiography. The 30 RA patients included in the study were diagnosed according to the 2010 ACR-EULAR criteria. Disease activity was measured by the disease activity score (DAS28) index.Results: Group 1 included 30 patients with RA and group 2 included 30 age and sex-matched controls. Pearson correlation analysis was done between EFT and other variables. Only HDL, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hS-CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), DAS28, and disease duration were found to have a significant correlation with EFT.Conclusion: In patients with RA, EFT, left ventricular mass, and diastolic dysfunction are increased in RA patients compared to healthy controls. Out of the conventional CVD risk factors, only HDL was associated with increased EFT in RA patients. In RA patients, DAS28, disease duration, RF, anti-CCP, and markers of inflammation (ESR, hs-CRP) were also associated with increased EFT.

Association among B lymphocyte subset and rheumatoid arthritis in a Chinese population

Background and aimAutoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters.MethodsIn total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction.ResultsThe percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing RA was 0.831 (95% CI 0.748 ~ 0.915), the specificity was 91.4%, and the sensitivity was 67.5%. The AUC predicted by the combination of plasmablast and anti-CCP for active RA patients was 0.760, which was higher than that of plasmablast and anti-CCP.ConclusionIn conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA.

Anti-cyclic citrullinated peptide antibody (ACPA) and Rheumatoid arthritis: Clinical relevance

Rheumatoid Arthritis (RA) is the most common auto-immune, chronic inflammatory joint disease. Predominantly a musculoskeletal condition with a wide spectrum of skeletal and extra-skeletal manifestations, RA has a significant footfall in orthopaedic clinical practice worldwide.RA is essentially a clinical diagnosis; however, laboratory and radiographic investigations can provide complementary diagnostic and prognostic information about the disease. Early diagnosis and initiation of appropriate management are crucial since RA patients can develop chronic, erosive arthritis if left untreated or if treatment is delayed.Rheumatoid Factor (RF) antibody test is routinely employed for diagnostic purposes in patients with suspected RA. However, RF is present only in 70%–80% of patients with RA and can be non-specific. Therefore, Anti-cyclic citrullinated peptide antibody (ACPA), a novel immunological marker for RA is increasingly being utilised to provide higher specificity and a better prognostic indicator in RA patients.We describe the immunological basis of ACPA test and highlight its current applications in the diagnosis, prognosis and monitoring of RA in clinical practice.

Elevated Fab glycosylation of anti-hinge antibodies

Objective Rheumatoid arthritis (RA) is characterized by systemic inflammation and the presence of anti-citrullinated protein antibodies (ACPAs), which contain remarkably high levels of Fab glycosylation. Anti-hinge antibodies (AHAs) recognize immunoglobulin G (IgG) hinge neoepitopes exposed following cleavage by inflammation-associated proteases, and are also frequently observed in RA, and at higher levels compared to healthy controls (HCs). Here, we investigated AHA specificity and levels of Fab glycosylation as potential immunological markers for RA. Method AHA serum levels, specificity, and Fab glycosylation were determined for the IgG1/4-hinge cleaved by matrix metalloproteinase-3, cathepsin G, pepsin, or IdeS, using enzyme-linked immunosorbent assay and lectin affinity chromatography, in patients with early active RA (n = 69) and HCs (n = 97). Results AHA reactivity was detected for all hinge neoepitopes in both RA patients and HCs. Reactivity against CatG-IgG1-F(ab´)2s and pepsin-IgG4-F(ab´)2s was more prevalent in RA. Moreover, all AHA responses showed increased Fab glycosylation levels in both RA patients and HCs. Conclusions AHA responses are characterized by elevated levels of Fab glycosylation and highly specific neoepitope recognition, not just in RA patients but also in HCs. These results suggest that extensive Fab glycosylation may develop in response to an inflammatory proteolytic microenvironment, but is not restricted to RA.