Early Stage Of Rheumatoid Arthritis Research Articles

Targeting Oxidative Stress Markers, Xanthine Oxidase, TNFRSF11A and Cathepsin L in Curcumin-Treated Collagen-Induced Arthritis: A Physiological and COSMO-RS Study.

The effectiveness of curcumin in preventing and treating collagen-induced inflammatory arthritis (CIA) in rats and oxidative stress in rats was investigated. We investigated curcumin's curative and preventive effects on paw edema, arthritic size, body weight, and radiologic and histological joint abnormalities. It has been shown that curcumin may dramatically lower the risk of developing arthritis. In addition, the number of white blood cells (WBCs) in the body has dropped, which is a strong indication that curcumin has anti-inflammatory characteristics. A follow-up theoretical investigation of curcumin molecular docking on xanthine oxidase (XO) was carried out after the properties of curcumin were determined using the conductor-like screening model for real solvents (COSMO-RS) theory. Because of the interaction between curcumin and the residues on XO named Ile264, Val259, Asn351, and Leu404, XO may be suppressed by this molecule. Curcumin's anti-inflammatory and antioxidant properties may be responsible for the anti-arthritic effects that have been seen on oxidative stress markers and XO. On the other hand, more research is being conducted to understand its function better in the early stages of rheumatoid arthritis (RA). To determine whether or not curcumin interacts with AR targets, a molecular docking study was conducted using MVD software against TNFRSF11A and cathepsin L.

Ultrasonography in Early Stage of Rheumatoid Arthritis and Psoriatic Arthritis: Review Article

Ultrasonography in Early Stage of Rheumatoid Arthritis and Psoriatic Arthritis: Review Article

Endothelial cell protein C receptor regulates neutrophil extracellular trap–mediated rheumatoid arthritis disease progression

Endothelial cell protein C receptor (EPCR) is a 46 kDa transmembrane protein receptor, expressed in most immune cells (T cells, monocytes, dendritic cells, polymorphonuclear neutrophils [PMN]). EPCR reportedly plays a vital role in rheumatoid arthritis (RA). Our results confirmed that EPCR expression exists in the PMN of RA patients, and animal experiments demonstrated that down-regulation of EPCR expression affects disease progression in collagen-induced arthritis (CIA) mice. PMN is the immune cell type that first enters the site of inflammation in the early stages of inflammation. In the early stage of RA, PMN cells migrate into the joint cavity and function in the process of RA synovial inflammation, aggravating the bone destruction found in RA and mediating the progression of RA disease progression. We verified the differences in EPCR expression in PMN cells between RA and osteoarthritis (OA) patients by Western blot and then confirmed this difference in animals. We found that CIA mice treated with PMN-neutralizing antibody intervention had reduced disease performance. On this basis, EPCR was knocked down at the same time. The therapeutic effect of PMN-neutralizing antibody treatment was subsequently diminished. To explore the relationship between EPCR and PMN in RA, we used immunofluorescence to detect the expression of PMN–neutrophil extracellular traps (NETs) in RA patients and used EPCR neutralizing antibodies as an intervention. The results showed that the formation of PMN-NETs in RA patients increased. Finally, through in vitro intervention experiments involving EPCR and PMN transcriptome analysis of the peripheral blood of RA patients, we concluded that EPCR may regulate the formation of PMN-NETs in RA patients through the activated protein C (APC)-EPCR signaling pathway, thereby affecting the progression of disease in RA patients.

Telomeres Length Variations in a Rheumatoid Arthritis Patients Cohort at Early Disease Onset and after Follow-Up.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial joint inflammation, progressive disability, premature immune aging, and telomere length (TL) shortening. The objective of the study was to study TL changes in patients at early disease onset and after follow-up. Relative leukocyte TL (rLTL) was measured by quantitative polymerase chain reaction (qPCR) in 88 at-admission patients (AAP) with < 1 year of symptoms onset, self-compared after follow-up, and a reference group of sex- and age-matched healthy individuals. Correlations between rLTL percentage change after variable disease exposure time (DET) and clinical laboratory disease activity markers and treatments were assessed. Non-parametrical statistics were applied, considering < 0.05 p-value significant. The median (p25, p75) rLTL was lower in patients after DET (0.61, 0.49-0.70) than in AAP (0.64, 0.50-0.77), p = 0.017. Furthermore, telomeres at early stages of RA were shorter than in the reference group (0.77, 0.59-0.92; p = 0.003). HLA-DRB1*04 allele carrier status did not significantly affect rLTL at an early stage and after follow-up. The patients' rLTL shortening was mainly associated with longer at-admission telomeres (OR 16.2, 95%CI: 3.5-74.4; p < 0.0001). At follow-up, RA patients showed significantly shorter rLTL than AAP, particularly in those AAP with longer telomeres, disregarding disease activity and treatments, denoting an rLTL shortening effect influenced by age, DET, and native rLTL.

A 3-Dimensional Gait Analysis of the Effects of Fatigue-Induced Reduced Foot Adductor Muscle Strength on the Walking of Healthy Subjects.

Dysfunction of the tibialis posterior muscle is the most common cause of adult acquired flat foot. Tibialis posterior muscle weakness has been observed in several patient populations, including those in the early stages of rheumatoid arthritis. However, the influence of tibialis posterior weakness on gait mechanics is not fully understood, although gait instability has been reported. In 24 healthy participants, 3-dimension lower limb kinematics and kinetics during walking were evaluated bilaterally, before and after, a muscle fatigue protocol aiming to decrease the right foot adductor muscles strength, including the tibialis posterior muscle. The 3-dimension gait kinematics and kinetics were analyzed with statistical parametric mapping. The stance phase duration was increased for the right side. The right ankle external rotation moment decreased, and the left hip extension moment increased with reduced muscle strength compared with normal strength conditions. These changes are similar in patients with dysfunction in the tibialis posterior muscle, indicating that compensatory strategies observed in these patients might be related to the loss of tibialis posterior muscle strength. Such strategies may involve the unaffected side.

Evaluation of the adipokine profile (adiponectin, resistin, adipsin, vaspin, and leptin) in patients with early rheumatoid arthritis and its correlation with disease activity

IntroductionAdipokines may play a role in the early stages of rheumatoid arthritis. This study evaluated the performance of adipokines in a Colombian population with early rheumatoid arthritis and its relationship with disease activity.Material and methodsA cross-sectional study evaluated serum adipokine levels (adiponectin, resistin, adipsin, vaspin, and leptin) in patients with early rheumatoid arthritis (eRA), evaluating demographic and clinical variables, along with a control group matched by age and gender. A factorial analysis was performed using principal components analysis (PCA), and a Spearman correlation analysis was performed. Similarly, a cut-off point for serum levels is proposed based on the receiver operating characteristic (ROC) curve between eRA and controls and sensitivity analysis.ResultsFifty-one eRA subjects were included; there were 41 women. The body mass index (BMI) was 25.12 ±3.8. A statistically significant correlation was identified between adipsin, BMI, and RAPID3. Vaspin and leptin were correlated with BMI. Resistin levels were higher in patients with RAPID3 near remission (p = 0.041), and adiponectin, vaspin, and leptin levels were lower in patients with DAS28 ESR in remission (p = 0.033, p = 0.012, and p = 0.017, respectively). Principal components analysis in component 1 adipokines as adipsin and leptin with BMI and RAPID3 as disease activity index are grouped. Moreover, component 2 had a strong relation between ESR and CRP with an inverse correlation with cholesterol levels and vaspin. A cut-off point was established for each adipokine, thus identifying the best performance for leptin levels greater than 0.58 ng/ml with a sensitivity of 76.5% and specificity of 74.5%.ConclusionsAdipokine levels are relevant in eRA, especially with disease activity indexes. Resistin levels were higher in patients with an activity index near remission. Otherwise, adiponectin, vaspin, and leptin levels were lower in patients with low activity indexes. RAPID3 correlated with adipsin. It is complementary to the previously published analysis of adipokines.

A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities.

Metabolomic analysis provides a wealth of information that can be predictive of distinctive phenotypes of pathogenic processes and has been applied to better understand disease development. Rheumatoid arthritis (RA) is an autoimmune disease with the establishment of chronic synovial inflammation that affects joints and peripheral tissues such as skeletal muscle and bone. There is a lack of useful disease biomarkers to track disease activity, drug response and follow-up in RA. In this review, we describe potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities. TMAO (choline and trimethylamine oxide) and TCA (tricarboxylic acid) cycle products have been suggested to modulate metabolic profiles during the early stages of RA and are present systemically, which is a relevant characteristic for biomarkers. Moreover, the analysis of lipids such as cholesterol, FFAs and PUFAs may provide important information before disease onset to predict disease activity and treatment response. Regarding therapeutics, TNF inhibitors may increase the levels of tryptophan, valine, lysine, creatinine and alanine, whereas JAK/STAT inhibitors may modulate exclusively fatty acids. These observations indicate that different disease modifying antirheumatic drugs have specific metabolic profiles and can reveal differences between responders and non-responders. In terms of comorbidities, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. In conclusion, synovial fluid, blood and urine samples from RA patients seem to provide critical information about the metabolic profile related to drug response, disease activity and comorbidities.

Increased Frequency of CD4+ Follicular Helper T and CD8+ Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis.

Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy. In the blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissues, Tfh cells were localized in B-cell areas, and their frequency correlated with the frequency of CD19+ B cells. Compared to lymphoid tissues of healthy controls, those of RA patients and RA-risk individuals showed more CD19+ B cells, CD4+CXCR5+ follicular helper T cells, and CD8+CXCR5+ follicular T cells. These Tfh cells produced less IL-21 upon ex vivo stimulation. These findings suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression.

Extracellular pyruvate kinase M2 promotes osteoclastogenesis and is associated with radiographic progression in early rheumatoid arthritis

Extracellular PKM2 (exPKM2) levels have been reported to be increased in several cancers and inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to investigate the association of circulating exPKM2 levels with radiographic progression in RA patients and the effect of exPKM2 on osteoclastogenesis. Plasma and synovial fluid exPKM2 levels were significantly elevated in RA patients. Plasma exPKM2 levels were correlated with RA disease activity and were an independent predictor for radiographic progression in RA patients with a disease duration of ≤ 12 months. CD14+ monocytes but not RA fibroblast-like synoviocytes secreted PKM2 upon stimulation with inflammatory mediators. Recombinant PKM2 (rPKM2) increased the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and resorption pit in osteoclast precursors, dose-dependently, even in the absence of receptor activator of nuclear factor-kappa B ligand (RANKL). rPKM2 treatment upregulated the expression of dendrocyte-expressed seven transmembrane protein (DC-STAMP) and MMP-9 via the ERK pathway. Although rPKM2 did not directly bind to RAW264.7 cells, extracellular application of pyruvate, the end-product of PKM2, showed effects similar to those seen in rPKM2-induced osteoclastogenesis. These results suggest that exPKM2 is a potential regulator of RA-related joint damage and a novel biomarker for subsequent radiographic progression in patients with early-stage RA.

VHPKQHR Peptide Modified Ultrasmall Paramagnetic Iron Oxide Nanoparticles Targeting Rheumatoid Arthritis for T1-Weighted Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) could be the ideal diagnostic modality for early rheumatoid arthritis (RA). Vascular cell adhesion molecule-1 (VCAM-1) is highly expressed in synovial locations in patients with RA, which could be a potential target protein for RA diagnosis. The peptide VHPKQHR (VHP) has a high affinity to VCAM-1. To make the contrast agent to target RA at an early stage, we used VHP and ultrasmall paramagnetic iron oxide (USPIO) to synthesize UVHP (U stands for USPIO) through a chemical reaction with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide. The size of UVHP was 6.7 nm; the potential was −27.7 mV, and the r 2/r 1 value was 1.73. Cytotoxicity assay exhibited that the cell survival rate was higher than 80% at even high concentrations of UVHP (Fe concentration 200 µg/mL), which showed the UVHP has low toxicity. Compared with no TNF-α stimulation, VCAM-1 expression was increased nearly 3-fold when mouse aortic endothelial cells (MAECs) were stimulated with 50 ng/mL TNF-α; cellular Fe uptake was increased very significantly with increasing UVHP concentration under TNF-α treatment; cellular Fe content was 17 times higher under UVHP with Fe concentration 200 µg/mL treating MAECs. These results indicate that UVHP can target overexpression of VCAM-1 at the cellular level. RA mice models were constructed with adjuvant-induced arthritis. In vivo MRI and biodistribution results show that the signal intensity of knee joints was increased significantly and Fe accumulation in RA model mice compared with normal wild-type mice after injecting UVHP 24 h. These results suggest that we have synthesized a simple, low-cost, and less toxic contrast agent UVHP, which targeted VCAM-1 for early-stage RA diagnosis and generates high contrast in T1-weighted MRI.

Quantum-Inspired Interpretable AI-Empowered Decision Support System for Detection of Early-Stage Rheumatoid Arthritis in Primary Care Using Scarce Dataset

Rheumatoid arthritis (RA) is a chronic inflammatory and long-term autoimmune disease that can lead to joint and bone erosion. This can lead to patients’ disability if not treated in a timely manner. Early detection of RA in settings such as primary care (as the first contact with patients) can have an important role on the timely treatment of the disease. We aim to develop a web-based Decision Support System (DSS) to provide a proper assistance for primary care providers in early detection of RA patients. Using Sparse Fuzzy Cognitive Maps, as well as quantum-learning algorithm, we developed an online web-based DSS to assist in early detection of RA patients, and subsequently classify the disease severity into six different levels. The development process was completed in collaborating with two specialists in orthopedic as well as rheumatology orthopedic surgery. We used a sample of anonymous patient data for development of our model which was collected from Shohada University Hospital, Tabriz, Iran. We compared the results of our model with other machine learning methods (e.g., linear discriminant analysis, Support Vector Machines, and K-Nearest Neighbors). In addition to outperforming other methods of machine learning in terms of accuracy when all of the clinical features are used (accuracy of 69.23%), our model identified the relation of the different features with each other and gave higher explainability comparing to the other methods. For future works, we suggest applying the proposed model in different contexts and comparing the results, as well as assessing its usefulness in clinical practice.

Observation of the curative effect of Guizhi-Shaoyao-Zhimu decoction combined with methotrexate in the treatment of early rheumatoid arthritis based on ultrasonic evaluation: study protocol of a randomized, double-blind, controlled clinical trial

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with the primary clinical symptoms of joint swelling and pain. Early detection of erosion and synovial inflammation at an active stage resulting from RA can prevent damage to the joints and activity restriction. However, there are still many patients who do not respond to these treatments; the development of newer, safer drugs is urgently needed. Compared to Western medicine, Guizhi-Shaoyao-Zhimu decoction has equal or higher efficacy and safety for RA patients. With the widespread use of musculoskeletal ultrasound (MSUS), this technology holds great value for the degree of joint damage in RA patients, guiding the clinical selection of treatments, and assessing of prognosis. Therefore, we designed a double-blinded randomized controlled clinical trial to measure the safety and efficacy of Guizhi-Shaoyao-Zhimu decoction in treating early-stage RA using MSUS.MethodsThis study is a randomized, double-blinded, parallel group, placebo-controlled trial. A total of 152 adult participants with early RA will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be Guizhi-Shaoyao-Zhimu decoction plus the conventional medicine methotrexate and the control intervention will be placebo plus the conventional drug methotrexate for 3 months. In addition, both groups will receive folic acid during treatment to prevent side effects from methotrexate. The primary outcomes are the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hepatic and renal function, visual analog scale, disease activity score in 28 joints, measurement scale for TCM symptoms, and 7-joint ultrasound score.DiscussionWe designed this double-blinded randomized controlled clinical trial to evaluate the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in RA patients using MSUS. The results of this trial may provide insights into how to improve the clinical symptoms of RA patients and delay further joint destruction. We hope that this trial may provide preliminary evidence of the efficacy of Guizhi-Shaoyao-Zhimu decoction in treating RA patients and that these results aid researchers, practitioners, and patients alike.AimThe main aim of the study is to clarify the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in patients with early RA.Trial registrationChinese Clinical Trials Register ChiCTR2000036141. Registered on 21 August 2020 (retroactively registered)

Can an Infection with SARS COV-2 cause or Exacerbate Rheumatoid Arthritis? Description of A Clinical Case

Infectious disease can activate the immune system favoring a highly inflammatory response. Rheumatoid Arthritis is a long term inflammatory disease characterized by an autoimmune trigger. What happens when SARS COV 2 infection occurs in a patient suffering from early stage of rheumatoid arthritis? In this clinical case we want to highlight that the infection by SARS COV 2 could esacerbate or precipitate a clinical picture of Rheumatoid Arthritis. This condition should make you reflect on the probable therapeutic implications.

Directional self-assembly of anisotropic bimetal-poly(aniline) nanostructures for rheumatoid arthritis diagnosis in multiplexing

Anisotropic organic-inorganic hybrid nanoparticles possessing different functionalities and physicochemical properties from each compartment have attracted significant interest for the development of advanced functional materials. Moreover, their self-assembled structures exhibit unique optical properties for photonics-based biosensing. We report herein the fabrication of anisotropic bimetal-polymer nanoparticles (ABPNs) via combination of oxidative polymerization and additional growth of metallic nanoparticles on Au seeds as well as their directional clustering mediated via noncovalent interactions. Polymerization of anilines for poly (aniline) shell was conducted by reducing silver nitrate onto the Au seed in the presence of a surfactant, giving rise to spatially distinct bimetallic Au core and Ag shell compartment and the poly (aniline) counter-one that comprise the ABPNs. Furthermore, ABPNs were directionally clustered in a controlled manner via hydrophobic interaction, when the bimetallic compartment was selectively modified. These nanoclusters showed highly enhanced optical properties owing to the increased electromagnetic fields while the poly (aniline) being used to offer antibody binding capacity. Taking advantages of those properties of the ABPN nanoclusters, surface-enhanced Raman scattering (SERS) intensity-based quantification of two different biomarkers: autoantibodies against cyclic citrullinated peptide and rheumatoid factor was demonstrated using ABPN nanoclusters as SERS nanoprobes. Conclusively, this work has great potential to satisfy a need for multiplexing in diagnosis of early stage of rheumatoid arthritis.

POS0575 THE PATIENT GLOBAL ASSESSMENT (PGA) OF DISEASE ACTIVITY COLLECTS DIFFERENT INFORMATION IN EARLY COMPARED TO ESTABLISHED RHEUMATOID ARTHRITIS

Background:The patient global assessment (PGA) is the most widely used patient-reported measure in rheumatoid arthritis (RA), being a component of disease activity scores and definitions of remission. Studies have however shown that, at least in established RA, PGA is mostly associated with pain, functional limitation, psychological distress and comorbidities, rather than with objective measures of inflammation. As such, the inclusion of PGA as a driver of intensification of immunosuppressive therapy is been questioned. Determinants of PGA may however differ in the earliest stages of RA, when pain processing mechanisms and damage accrual have not occurred yet. Whether the association of PGA with disease activity in RA changes over time is at present undetermined.Objectives:To analyze the associations between PGA and disease activity measures in patients with RA across different phases of the disease.Methods:1.002 RA patients from two independent cohorts were included: 1) a prospective longitudinal cohort of early RA (&lt;12 months of symptoms) (n=601) with an observation period of 24 months upon initiation of therapy with methotrexate; 2) a cross-sectional cohort of established RA (duration &gt;5 years) (n=401) with inadequate response to methotrexate. Determinants of PGA were assessed by Pearson’s correlation coefficients and multivariable linear regression.Results:In early RA, median (IQR) symptom duration at inclusion was 15 (9-27) weeks, 71.5% of the patients were female, 49.3% were autoantibody-positive, and 30% had radiographic evidence of ≥1 erosion. The mean (SD) DAS28 was 4.94 (1.19), and the mean (SD) PGA 57.6 (26.6). The proportion of patients at least in low disease activity (DAS28 &lt;3.2) after 6, 12 and 24 months of treatment was 49.9%, 57.4% and 67% respectively. The associations of PGA with pain and functional limitation were moderate to good (r &gt;0.40) at all time points, and were independent of other co-variates (Table 1). Swollen joints (SJC28) were independently and directly associated with PGA at all time points until 12 months, whilst the association become indirect at 24 months (Table 1). In ACPA-positive patients, PGA at 6 and 12 months was weakly but still significantly associated with SJC28 even in low disease activity states (adj r 0.15 and 0.13, p&lt;0.05). Patients with established RA had a mean [SD] DAS28 of 5.3 [1.2] and were ACPA-positive in 69.6% of the cases. Independent determinants of PGA were pain, HAQ and tender joints, whilst no associations with SJC28 and acute phase reactants were found neither in the overall cohort nor in ACPA-positive patients.Conclusion:In established RA, PGA appears mostly related to factors outside the core domains of disease activity. In contrast, in the early phases of the disease, PGA may more strictly collect information on inflammatory-related symptoms. Better understanding of the relationship between patient reported outcomes and disease activity in the various phases of RA may thus be needed before introducing definitive changes in the current definitions of disease activity.

Longitudinal Changes in Knee Joint Synovial Vascularity in a Rabbit Model of Rheumatoid Arthritis: Quantification Using Power Doppler Ultrasound and Contrast-Enhanced Ultrasound

We studied a rabbit model of rheumatoid arthritis (RA) to examine the time course of changes in synovial neovascularization based on quantitative power Doppler ultrasound and contrast-enhanced ultrasound (CEUS). Twenty-five male New Zealand rabbits were in the ovalbumin-induced arthritis (OIA) group, and 5 were in the control group. Both rear knee joints of all rabbits were examined using conventional US and CEUS over 16 weeks. The knee synoviums of OIA rabbits were sampled by US-guided biopsy, and expression of CD31 and vascular endothelial growth factor (VEGF) was determined by immunohistochemistry. The correlation of joint damage based on multimodal US with microvessel density (CD31 positivity) and VEGF expression at different times was analyzed. OIA rabbits had increased synovial expression of CD31 and VEGF from weeks 6 to 12 (p < 0.01). During the early stage of CEUS enhancement, “dot enhancement” was more common at weeks 6 and 8, and “stripe enhancement” was more common at weeks 12 and 16 (p < 0.05). There were significant positive correlations of synovial CD31 and VEGF expression with power Doppler image grade, CEUS grade and peak intensity (p < 0.05 for all). Thus, OIA rabbits mimicked early-stage RA at 6 to 8 weeks, middle-stage RA at 8 to 12 weeks and late-stage RA at 12 to 16 weeks. Power Doppler image grade, CEUS grade and peak intensity, especially when combined with CD31 expression data, accurately characterized the extent of synovial vascularization in a rabbit model of RA. Increased vascularity based on CEUS may have value for the early diagnosis of RA.

Significance of Hyaluronic acid as a biomarker with seropositive and seronegative autoantibodies in Rheumatoid arthritis patients

Testing for autoantibodies is a flagship feature of Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disorder affecting both the male and female population. Synovial inflammation followed by cartilage, bone, and joint destruction in the later stages of RA puts life in peril, especially for those with other comorbidities. In this study, we focused on to measure serum Hyaluronic acid (HA) along with seropositive and seronegative RF, AntiCCP autoantibodies to establish any association with these biomarkers. It was a cross-sectional study involving 152 RA patients based on the 1987 ACR criteria for the diagnosis of RA and 68 age‑ and sex-matched healthy controls. After clinical examination, the traditional markers were assessed to measure the disease activity, such as CRP, ESR, Anti -CCP, and RF in RA patients. The serum HA levels were measured using the ELISA method. All the values were expressed as median (25th–75th percentile). Based on seropositive and seronegative RF and AntiCCP autoantibodies, the patient group was divided into four groups- both seropositive, both seronegative, and the other two mixed groups. The traditional inflammatory markers were significantly increased in RA patients than in controls with (p &lt; 0.001). In our study, there was a significant increase in serum HA levels in RA patients compared to healthy controls (p &lt; 0.03). The serum HA levels were significantly correlated with Anti-CCP, DAS‑28, CRP, and ESR in RA patients. At the same time, serum HA level is increased in the group with seropositive for both antibodies showing statistical significance. Conclusion- serum Hyaluronic acid is involved in synovial inflammation, manifesting a common triggering mechanism more with AntiCCP antibodies than RF, promising for better clinical utility in the early stages of rheumatoid arthritis.

Profiling of Serum Oxylipins During the Earliest Stages of Rheumatoid Arthritis.

Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes. In total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease-modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry. Univariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least-squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment-naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified. Oxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.

Angiogenic T-cells as biomarkers of subclinical vascular stiffness in very early rheumatoid arthritis patients

Background and Aims: Angiogenic T-cells (Tang) are involved in vascular homeostasis. Decreased Tang frequency was found in rheumatoid arthritis (RA) patients, associated with cardiovascular (CV) events. The aim of this study was to evaluate whether Tang cells could be associated with subclinical CV endpoints (subclinical atherosclerosis and vascular stiffness) in the very early stage of RA

Induction of remission in female rheumatoid arthritis patients is associated with stabilization of myocardial abnormalities: a prospective cardiac magnetic resonance follow-up study

Objectives: To study whether female patients with active rheumatoid arthritis (RA) have myocardial abnormalities and whether progression of myocardial involvement can be attenuated by disease-modifying anti-rheumatic drugs (DMARDs). Method: Cardiac magnetic resonance (cMR; 1.5 or 3.0 T), including late gadolinium enhancement (LGE), T1 relaxation time, and ventricular functions, was performed in 30 patients with untreated active early RA starting first DMARDs, and 28 patients with chronic RA with inadequate response to conventional synthetic DMARDs starting biological DMARDs. cMR was repeated in RA patients 1 year later. cMR was conducted once in 22 fibromyalgia (FM) subjects and in 35 healthy volunteers serving as controls. All subjects were non-smoking females without coronary heart disease, heart failure, or diabetes. Results: Compared with controls, 58 RA patients had slightly lower ventricular function, although in the normal range, and longer T1 time at baseline. None of the FM subjects had LGE, but it was frequent in RA (67%). During the 1 year DMARD treatment, Disease Activity Score based on 28-joint count–C-reactive protein declined, ventricular functions tended to improve, but the number of patients with LGE remained unchanged. However, the number of LGE-positive heart segments either decreased or stayed the same in 91% of RA patients. In early RA patients, achieving tight remission was associated with LGE stabilization, after adjustment for age, metabolic syndrome, baseline inflammatory activity, and leisure-time physical activity. Conclusion: Treatment targeted to tight remission in early stages of RA seems to be important to prevent not only joint damage but also myocardial abnormalities.