Persistent Synovitis Research Articles

Disparities in rheumatoid arthritis outcomes for North American Indigenous populations

ABSTRACT Advances in rheumatoid arthritis (RA) management have significantly improved clinical outcomes of this disease; however, some Indigenous North Americans (INA) with RA have not achieved the high rates of treatment success observed in other populations. We review factors contributing to poor long-term outcomes for INA with RA. We conducted a narrative review of studies evaluating RA in INA supplemented with regional administrative health and clinical cohort data on clinical outcomes and health care utilisation. We discuss factors related to conducting research in INA populations including studies of RA prevention. NA with RA have a high burden of genetic and environmental predisposing risk factors that may impact disease phenotype, delayed or limited access to rheumatology care and advanced therapy. These factors may contribute to the observed increased rates of persistent synovitis, premature end-stage joint damage and mortality. Novel models of care delivery that are culturally sensitive and address challenges associated with providing speciality care to patients residing in remote communities with limited accessibility are needed. Progress in establishing respectful research partnerships with INA communities has created a foundation for ongoing initiatives to address care gaps including those aimed at RA prevention. This review highlights some of the challenges of diagnosing, treating, and ultimately perhaps preventing, RA in INA populations.

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.

A comparison of patient reported outcomes in rheumatoid arthritis treated by tofacitinib versus methotrexate

Background: Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease characterized by systemic inflammation, persistent synovitis, and joint destruction. 1 Patients and physicians rate RA disease differently — while physicians focus on RA-specific clinical and radiographic outcomes, patients focus on how their general health is affected by RA, which may lead to discordance. Aim and Objectives: The present study plans to compare the patient reported outcomes (PRO) in RA patients treated with Methotrexate or Tofacitinib. This study was done to compare the PRO in patients taking Tofacitinib or Methotrexate. Data from a 6-month analysis are reported here. Material and Methods: Patients presenting to outpatient department of department of orthopedics were included in this study. Patients above 18 years of age who have been previously or newly diagnosed with RA according to American College of Rheumatology criteria were included in this study. Patients were randomized into two groups who received either Tofacitinib 5 mg twice a day or Methotrexate 10 mg/week which was increased by 2.5 mg/week every 15 days to a maximum of 20 mg/week. Patient assessment was done by Visual Analog Scale (VAS) for pain and health assessment questionnaire-disability index (HAQ-DI). This will be done at starting of treatment and then at months 1, 2, 3, and 6. Results: Seventy-five patients received tofacitinib and 77 patients received methotrexate. There was an improvement in the disease condition as seen by VAS scale and HAQ-DI score of patients taking tofacitinib compared to methotrexate at 2, 3, and 6 months, and this difference was statistically significant. Conclusion: Tofacitinib has a safety and efficacy profile which is similar to or superior to methotrexate.

The Clinical Utility of Musculoskeletal Ultrasound for Disease Activity Evaluation and Therapeutic Response Prediction in Rheumatoid Arthritis Patients: A Narrative Review.

Rheumatoid arthritis (RA) is characterized by persistent synovitis and joint/bone destruction. There is an unmet need to predict the therapeutic response to disease-modifying anti-rheumatic drugs (DMARDs) and achieve a treat-to-target goal. Musculoskeletal ultrasound (MSUS) is widely used to identify structural change and assess therapeutic response in RA. This review aims to summarize the available evidence regarding the clinical application of MSUS in evaluating disease activity and predicting therapeutic responses to DMARDs. We searched the MEDLINE database using the PubMed interface and reviewed English-language literature from 2000 to 2022. This review focuses on the updated role of MSUS in assessing disease activity and predicting therapeutic responses to DMARDs in RA patients. MSUS is now widely applied to identify articular structural change and assess the disease activity of RA. Combined use of gray scale and power Doppler MSUS is also superior to clinical assessment and laboratory examination in evaluating disease activity of RA. With portable use, good viability, and high sensitivity to articular inflammation, MSUS would be useful in assessing therapeutic response to biologic/targeted synthetic DMARDs (b/tsDMARDs) in RA patients. Given MSUS could also detect subclinical inflammation in a substantial proportion of RA patients with clinical remission, it is recommended to assess b/tsDMARDs-treated RA patients who have achieved low disease activity or remission. Although substantial literature data have revealed clinical utility of MSUS for monitoring disease activity and evaluating therapeutic response in RA patients, the evidence regarding its predictive value for the effectiveness of b/tsDMARDs is limited.

Current Immunotherapy Strategies for Rheumatoid Arthritis: The Immunoengineering and Delivery Systems

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease accompanied by persistent multiarticular synovitis and cartilage degradation. The present clinical treatments are limited to disease-modifying anti-rheumatic drugs (DMARDs) and aims to relieve pain and control the inflammation of RA. Despite considerable advances in the research of RA, the employment of current clinical procedure is enormous, hindered by systemic side effect, frequent administration, tolerance from long-lasting administration, and high costs. Emerging immunoengineering-based strategies, such as multiple immune-active nanotechnologies via mechanism-based immunology approaches, have been developed to improve specific targeting and to reduce adverse reactions for RA treatments. Here, we review recent studies in immunoengineering for the treatment of RA. The prospect of future immunoengineering treatment for RA has also been discussed.

Rupture of the extensor digitorum communis tendon in extensor zone V due to plant thorn injuries: a report of two cases

Penetrating injuries due to a plant thorn in the hand may occur during outdoor activities. We experienced two patients with rupture of the extensor digitorum communis (EDC) tendon in extensor zone V caused by plant thorn injuries. Both patients, presenting with pain and swelling around the third metacarpophalangeal joint, had a history of penetrating injuries due to plant thorns. The injuries had been ineffectively treated with oral antibiotics. Plain radiographs showed soft tissue swelling without a foreign body and bony lesions. Enhanced magnetic resonance imaging confirmed a rupture of the EDC tendon at the third extensor zone V. Tendon ruptures were diagnosed 27 and 60 days after injury, respectively. A plant thorn injury in the hand can cause persistent synovitis around the tendon, and as a result, progress to tendon rupture. A magnetic resonance imaging examination may be helpful if symptoms do not improve for a prolonged period after plant thorn injury.

Disease-modifying anti-rheumatic drugs improve the cardiovascular profile in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting about 0. 5-1% of the adult population and manifesting as persistent synovitis, systemic inflammation and production of autoantibodies. Patients affected by RA not only experience chronic disease progression, but are also burdened by a 1.5-fold increased cardiovascular (CV) risk, which is comparable to the risk experienced by patients with type 2 diabetes mellitus. RA patients also have a higher incidence and prevalence of coronary artery disease (CAD). Although RA patients frequently present traditional CV risk factors such as insulin resistance and active smoking, previous studies have clarified the pivotal role of chronic inflammation-driven by proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)-in accelerating the process of atherosclerosis and impairing the coagulation system. Over the last years, a number of studies have shown that disease-modifying anti-rheumatic drugs (DMARDs) reducing the inflammatory state in general improve the CV risk, however some drugs may carry some apparent negative effects. Thus, RA is a model of disease in which targeting inflammation may counteract the progression of atherosclerosis and reduce CV risk. Clinical and experimental evidence indicates that the management of RA patients should be tailored based on the positive and negative effects of DMARDs on CV risk together with the individual traditional CV risk profile. The identification of genetic, biochemical and clinical biomarkers, predictive of evolution and response to treatment, will be the next challenge for a precision approach to reduce the burden of the disease.

Effect of Folic Acid Conjugated Silver Nanoparticles in Treatment of RA Like Adjuvant Arthritis in Rats

Objective: Nano medicine has become one of the promising research areas, opening new horizons in disease diagnosis and treatment. Recent years have witnessed a surge in the development of Nano medicine for combating rheumatoid arthritis (RA), the most common autoimmune arthritis. RA is characterized by progressive inflammation and persistent synovitis, leading to joint destruction, functional incapability, and ultimately disability. Although there has been a tremendous evolution in disease assessment and treatment, many patients still fail to attain remission. Therefore, developing new drugs that specifically target inflamed joints and simultaneously attenuate other possible damages to healthy tissues is indispensable. This study was done to evaluate the potential of folic acid conjugated silver nanoparticles (FA-AgNPs) as RA therapy. Methods: In the CFA-arthritic rat model, FA-AgNPs & methotrexate were administered for 8 consecutive weeks. Therapeutic efficacy was evaluated by measuring paw volume, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) levels. For safety concerns, complete blood picture (CBC), liver and renal function tests were evaluated. Joints histological assessment was also carried out. Results: FA-AgNPs significantly reduced paw volume, paw weight, ESR, CRP, RF, TNF-α, and IL-6 levels compared with arthritic non-treated rats, demonstrating good anti-inflammatory activity. Likewise, histology of tarsal joints depicted comparatively lesser inflammatory cellular infiltration and diminished cartilage erosions. Methotrexate displayed comparable results. In contrast to methotrexate, FA-AgNPs showed normal CBC & significantly improved liver and renal function tests. Conclusion: FA-AgNPs exhibited substantial anti-arthritic activity. This notable anti-arthritic potential of FA-AgNPs was as good as the current standard treatment of methotrexate (MTX) with higher biosafety.

Anatomical 3 Ligaments Reconstruction for Symptomatic Thumb Carpometacarpal Joint Instability.

Thumb carpometacarpal (CMC) joint instability is thought to be a debilitating disorder and, if left untreated, develops joint persistent synovitis and osteoarthritis. In this study, we report a novel surgical technique reconstructing the anterior oblique ligament, the dorsoradial ligament, and the intermetacarpal ligament simultaneously using both the transverse carpal ligament, and the palmaris longus tendon. Six patients with a mean age of 44 years showing no osteoarthritic changes by the radiographical examination underwent our anatomical three ligaments reconstruction for persistent painful thumb CMC joint instability. Clinical results with the mean follow-up of 20 months demonstrated that the pain was subjectively improved in all patients, both the grip and the pinch strength were increased significantly and good functional motion of the thumb could be observed after the operation. These findings indicated that our surgical procedure could be one option of treatment of the symptomatic CMC joint instability in early-stage arthritis.

DNA Origami as a Nanomedicine for Targeted Rheumatoid Arthritis Therapy through Reactive Oxygen Species and Nitric Oxide Scavenging.

Rheumatoid arthritis (RA) severely threatens human health by causing inflammation, swelling, and pain in the joints and resulting in persistent synovitis and irreversible joint disability. In the development of RA, pro-inflammatory M1 macrophages, which express high levels of reactive oxygen species (ROS) and nitric oxide (NO), induce synovial inflammation and bone erosion. Eliminating ROS and NO in the inflamed joints is a potential RA therapeutic approach, which can drive the transition of pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype. Taking advantage of the intrinsic ROS- and NO-scavenging capability of DNA molecules, herein, we report the development of folic acid-modified triangular DNA origami nanostructures (FA-tDONs) for targeted RA treatment. FA-tDONs could efficiently scavenge ROS and NO and actively target M1 macrophages, facilitating the M1-to-M2 transition and the recovery of associated cytokines and biomarkers to the normal level. The therapeutic efficacy of FA-tDONs was examined in the RA mouse model. As validated by appearance, histological, and serum examinations, FA-tDONs treatment effectively alleviated synovial infiltration and cartilage damage, attenuating disease progression. This study demonstrated the usage of DNA origami for RA treatment and suggested its potential in other antioxidant therapies.

Interleukin 6 Concentration in Synovial Fluid of Patients with Inflammatory and Degenerative Arthritis

The present study aims to compare interleukin 6 concentration in synovial fluid in patients with known types of arthritis. Persistent synovitis without known markers, such as Rheumatoid Factor (RF), Anti- Citrullinated Protein Antibodies (ACPA), and genetic markers as HLA-B27, is not uncommon. It is valuable to determine the presence of chronic inflammation and put it in correlation with agerelated changes, which are especially relevant for middle-aged patients with mono- or oligoarthritis, when the dilemma to start disease-modifying drugs for inflammatory disease often is present. Interleukin 6 (IL-6) plays a significant role in chronic inflammation. IL-6 concentration in synovial fluid reflects the presence and activity of joint inflammation. Synovial fluid was obtained from 101 patients with chronic synovitis. IL-6 concentration was determined by the immunochemical luminescence method. The median IL-6 concentration in synovial fluid in patients with osteoarthritis (OA) was 138.0 pg/ml (interquartile range (IQR) 43.4 to 296.0); in patients with rheumatoid arthritis was 2516.5 pg/ml, (IQR 1136.0 to 25058.0); in reactive arthritis 2281.0 pg/ml (IQR 1392.0 to 8652.0); psoriatic arthritis 1964.0 pg/ml (IQR 754.0 to 7300.0); ankylosing spondylitis 2776.0 pg/ml (IQR 514.7, 3944.0); in a group with negative RF, ACPA and HLA-B27 inflammatory arthritis 2163.0 pg/ml (IQR 822.0 to 7875.0). There is statistically significant difference of IL-6 concentration comparing OA and each inflammatory arthritis group, p<0.0001. IL-6 detection in the synovial fluid is helpful in arthritis evaluation. The results show that an IL-6 level over 1000 pg/ml suggests the diagnosis of inflammatory arthritis.

Optimizing the anti-inflammatory strategies in (osteo)arthritis: local or systemic?

Arthritis is affecting millions of people globally, involvement and distribution depending on the type of arthritis. The most common arthritic conditions are osteoarthritis (OA) and rheumatoid arthritis (RA). Despite the pathogeneses being fundamentally different, both joint diseases share the same need for local treatment of synovitis. No current treatment can stop the progression of OA. Local articulate treatment including glucocorticoid (GC) injections, radiosynoviorthesis (RSO) and surgical synovectomy are the only options to relieve pain and temporally improve movability before surgical intervention. For RA, despite effective systemic treatments, similarly need for local articulate treatment is still present, especially early in the disease, but also in case of recurrent episodes of disease flare. Current evidence supports local GC injection as first line treatment for persistent synovitis in a single or a few joints. RSO provides an evident and effective alternative for GC refractory synovitis, especially in early RA. Surgical synovectomy is an invasive alternative, but with less documented efficacy. Whether one unsuccessful intraarticular GC injection is enough to change of mode of action for local treatment is still unclear and needs to be further investigated. In conclusion persistent single joint synovitis in OA and RA is well treated with local treatment. Intra-articular GC injection is considered as first line of treatment, but RSO provides an additional treatment alternative with less side effects and better evidence of efficacy than surgical synovectomy.

Emerging Targets for the Treatment of Osteoarthritis: New Investigational Methods to Identify Neo-Vessels as Possible Targets for Embolization.

Osteoarthritis (OA) is the major cause of disability, affecting over 30 million US adults. Continued research into the role of neovascularization and inflammation related to osteoarthritis in large-animal models and human clinical trials is paramount. Recent literature on the pathogenetic model of OA has refocused on low-level inflammation, resulting in joint remodeling. As a result, this has redirected osteoarthritis research toward limiting or treating joint changes associated with persistent synovitis. The overall goal of this review is to better understand the cellular and tissue-specific mechanisms of inflammation in relation to a novel OA treatment modality, Genicular Artery Embolization (GAE). This article also assesses the utility and mechanism of periarticular neovascular embolization for the treatment of OA with a particular emphasis on the balance between pro-angiogenic and anti-angiogenic cytokines, inflammatory biomarkers, and imaging changes.

PCBP1 is associated with rheumatoid arthritis by affecting RNA products of genes involved in immune response in Th1 cells

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent synovitis, in which T helper 1 (Th1) can promote the development of a pro-inflammatory microenvironment. Poly(rC)-binding protein 1 (PCBP1) has been identified as a promising biomarker of RA, while its molecular mechanisms in RA development are unknown. As a canonical RNA binding protein, we propose that PCBP1 could play roles in RA by affecting both expression and alternative splicing levels in Th1 cells. Here, microarray datasets (GSE15573 and GSE23561), including 102 peripheral blood mononuclear cell samples from 39 RA patients and 63 controls, were used to evaluate the PCBP1 expression changes in RA patients. High throughput sequencing data (GSE84702) of iron driven pathogenesis in Th1 cells were downloaded and reanalyzed, including two Pcbp1 deficiency samples and two control samples in Th1 cells. In addition, CLIP-seq data of PCBP1 in Jurkat T cells was also analyzed to investigate the regulatory mechanisms of PCBP1. We found PCBP1 were down-regulated in RA specimens compared with control. The result of differentially expressed genes (DEGs) showed that Pcbp1 silencing in Th1 cells affected the expression of genes involved in immune response pathway. Alternative splicing analysis also revealed that PCBP1-regulated alternative splicing genes (RASGs) were enriched in TNF-a/NF-κB signaling pathway, T cell activation, T cell differentiation and T cell differentiation associated immune response pathways, which were highly associated with RA. DEGs and RASGs by Pcbp1 deficiency in mice were validated in PBMCs specimens of RA patients by RT-qPCR. Investigation of the CLIP-seq data revealed PCBP1 preferred to bind to 3′UTR and intron regions. PCBP1-bound genes were also significantly associated with RASGs, identifying 102 overlapped genes of these two gene sets. These genes were significantly enriched in several immune response related pathways, including myeloid cell differentiation and positive regulation of NF-κB transcription factor activity. Two RA-related genes, PML and IRAK1, were screened from the above immune related pathways. These results together support our hypothesis that PCBP1 can regulate the expression of genes involved in immune response pathway, and can bind to and regulate the alternative splicing of immune response related genes in immune T cells, and ultimately participate in the molecular mechanism of RA, providing new research ideas and directions for clinical diagnosis and treatment.

Application of Intra-articular Corticosteroid Injection in Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is one of the common rheumatic diseases in pediatrics. Persistent synovitis and joint pain cause reduced range of motion, deformity and gait interruption, which are important reasons for children's disability and a decline in their quality of life. Rheumatology experts have explored good treatment strategies, among which intra-articular corticosteroid injections (IACIs) targeting joints can greatly reduce these systemic adverse reactions while still obtaining local anti-inflammatory effects. Local inhibition of synovitis by the use of steroid hormones in a joint cavity can avoid or reduce adverse reactions of systemic therapy, prevent or treat leg length variance and joint contracture, solve Baker's cyst, improve tenosynovitis, promote physical therapy and rehabilitation, make gait change smoothly, relieve pain, and restore joint function. Given the importance of IACIs in treating JIA, this paper reviewed the case selection, drug injection, dose selection, current anesthesia and injection techniques, the efficacy, recurrence, and influencing factors of IACIs, the management of physiotherapy intervention post-injection, the application of ultrasound guidance and the safety and complications of IACIs in children with JIA. This study aims to guide the use of IACIs for the best approach throughout the review.

Pain reduction by radiosynoviorthesis in rheumatism-induced synovitis of the elbow : Results of a retrospective multicenter data analysis

Radiosynoviorthesis (RSO) is anuclear medical local treatment modality for inflammatory joint diseases. It is indicated in patients with rheumatoid arthritis (RA) in joints with persistent synovitis despite adequate pharmacotherapy. Arthritis of the elbow joint occurs in up to2/3 of patients with RA. Intra-articular radiotherapy using the beta emitter [186Re] rhenium sulfide leads to sclerosis of the inflamed synovial membrane with subsequent pain alleviation. The clinical efficacy in cubital arthritis, however, has so far only been described in small monocentric studies. The degree of pain alleviation by RSO was analyzed in patients with rheumatoid cubital arthritis, treated in several nuclear medical practices specialized in RSO. The subjective pain intensity before and after RSO was documented in atotal of 107patients with rheumatic cubital arthritis using a10-step numeric rating scale (NRS). Adifference of ≥ -2 is rated as asignificant improvement. Follow-up examinations were done after amean interval of 14months after RSO (at least 3months, maximum 50months). The mean NRS value was 7.3 ± 2.1 before RSO and 2.8 ± 2.2 after RSO. Asignificant pain alleviation was seen in 78.5% of all patients treated. The subgroup analysis also showed asignificant improvement in the pain symptoms in all groups depending on the time interval between the RSO and the control examination. Asignificant pain progression was not observed. The degree of pain relief was independent of the time of follow-up. Using RSO for local treatment of rheumatoid cubital arthritis leads to asignificant and long-lasting pain relief in more than ¾ of the treated patients.

Peculiarities of knee replacement in patients with rheumatoid arthritis

Introduction. Rheumatoid arthritis (RA), as a steadily progressive disease leading to joint destruction and functional instability of the knee joints, often requires orthopedic correction.The aim. Of the review was to analyze the surgery strategy and technical features of knee arthroplasty and replacement in patients with RA.Basic provisions. RA is characterized by a number of abnormalities not only due to erosive arthritis and active persistent synovitis, but also caused by a decrease in bone mineral density, damage to the periarticular structures and patella, the formation of bone defects, as well as a high risk of postoperative complications. All these factors should be taken into account while choosing relevant surgical treatment and knee replacement technique. The article presents the optimal approaches for performing knee replacement in RA patients, taking into account the peculiarities of the existing structural and functional disorders.Conclusion. TEC in patients with RA requires a personalized approach based on evaluation of disease-associated risk factors affecting the results of orthopedic correction and the likelihood of complications.

Emerging Role of Eosinophils in Resolution of Arthritis.

Eosinophils are a minor component of circulating granulocytes, which are classically viewed as end-stage effector cells in host defense against helminth infection and promoting allergic responses. However, a growing body of evidence has emerged showing that eosinophils are versatile leukocytes acting as an orchestrator in the resolution of inflammation. Rheumatoid arthritis (RA) is the most common chronic inflammatory disease characterized by persistent synovitis that hardly resolves spontaneously. Noteworthy, a specific population of eosinophils, that is, regulatory eosinophils (rEos), was identified in the synovium of RA patients, especially in disease remission. Mechanistically, the rEos in the synovium display a unique pro-resolving signature that is distinct from their counterpart in the lung. Herein, we summarize the latest understanding of eosinophils and their emerging role in promoting the resolution of arthritis. This knowledge is crucial to the design of new approaches to rebalancing immune homeostasis in RA, considering that current therapies are centered on inhibiting pro-inflammatory cytokines and mediators rather than fostering the resolution of inflammation.

Identifying Immune Cell Infiltration and Effective Diagnostic Biomarkers in Rheumatoid Arthritis by Bioinformatics Analysis.

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by inflammatory cell infiltration, leading to persistent synovitis and joint destruction. The pathogenesis of RA remains unclear. This study aims to explore the immune molecular mechanism of RA through bioinformatics analysis.MethodsFive microarray datasets and a high throughput sequencing dataset were downloaded. CIBERSORT algorithm was performed to evaluate immune cell infiltration in synovial tissues between RA and healthy control (HC). Wilcoxon test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were conducted to identify the significantly different infiltrates of immune cells. Differentially expressed genes (DEGs) were screened by “Batch correction” and “RobustRankAggreg” methods. Functional correlation of DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Candidate biomarkers were identified by cytoHubba of Cytoscape, and their diagnostic effectiveness was predicted by Receiver Operator Characteristic Curve (ROC) analysis. The association of the identified biomarkers with infiltrating immune cells was explored using Spearman’s rank correlation analysis in R software.ResultsTen significantly different types of immune cells between RA and HC were identified. A total of 202 DEGs were obtained by intersection of DEGs screened by two methods. The function of DEGs were significantly associated with immune cells. Five hub genes (CXCR4, CCL5, CD8A, CD247, and GZMA) were screened by R package “UpSet”. CCL5+CXCR4 and GZMA+CD8A were verified to have the capability to diagnose RA and early RA with the most excellent specificity and sensitivity, respectively. The correlation between immune cells and biomarkers showed that CCL5 was positively correlated with M1 macrophages, CXCR4 was positively correlated with memory activated CD4+ T cells and follicular helper T (Tfh) cells, and GZMA was positively correlated with Tfh cells.ConclusionsCCL5, CXCR4, GZMA, and CD8A can be used as diagnostic biomarker for RA. GZMA-Tfh cells, CCL5-M1 macrophages, and CXCR4- memory activated CD4+ T cells/Tfh cells may participate in the occurrence and development of RA, especially GZMA-Tfh cells for the early pathogenesis of RA.

Exploring the role of monocyte chemoattractant protein-1 in fibroblast-like synovial cells in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is a chronic systemic inflammatory disease with persistent synovitis. In the present study, the impact of monocyte chemoattractant protein-1 (MCP-1) was explored to determine methods for the diagnosis and treatment of RA.MethodsFirst, fibroblast-like synoviocytes (FLSs) were obtained from a collagen-induced rat RA model. Next, MCP-1-overexpression plasmid and small interfering RNA were transfected into human and rat FLSs. Cell Counting Kit-8 (CCK-8), Transwell migration and flow cytometry assays were used to analyze cell proliferation, migration and apoptosis of FLSs following MCP-1 transfections, respectively. Furthermore, western blotting was used to analyze the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β in FLSs following MCP-1 transfection. In addition, reverse transcription-quantitative PCR and ELISAs were used to analyze the expression levels of C-reactive protein (CRP), estrogen receptor, MCP-1 and pentraxin-3 in patients with clinical RA, followed by correlation analysis of clinical data. Finally, expression validation, diagnostic and protein-protein interaction (PPI) network analysis of MCP-1 were performed.ResultsMCP-1 promoted FLS proliferation and migration, and affected the apoptosis of FLSs. In addition, the expression levels of p-P38, p-PI3K, PI3K, CD31, VEGF, TNF-α and IL-β were also affected by MCP-1. In patients with clinical RA, the expression level of MCP-1 was increased. Moreover, CRP expression level was significantly up-regulated in RA. Clinically, MCP-1 was strongly correlated with tender joint count, swollen joint count, visual analog scale for general health and disease activity score 28 (DAS28)-MCP-1, and was moderately correlated with DAS28 and DAS28-CRP. PPI analysis showed that MCP-1 mainly interacted with other inflammatory cytokines.ConclusionIn conclusion, MCP-1 may play a significant regulatory role in RA, and could be used as a measurement index of clinical RA activity.