Early Stage Of Rheumatoid Arthritis Research Articles

A responsive nanoplatform with molecular and structural imaging capacity for assisting accurate diagnosis of early rheumatoid arthritis

Accurate early diagnosis of rheumatoid arthritis (RA) and prompt implementation of appropriate treatment approaches are crucial. In the clinic, magnetic resonance imaging (MRI) has been recommended for implementation to aid in the precise and early diagnosis of RA. However, they are still limited by issues regarding specificity and their ability to capture comprehensive information about the pathological features. Herein, a responsive multifunctional nanoplatform with targeting capabilities (hMnO2-IR@BSA-PEG-FA) is constructed through integrating a RA microenvironment-responsive MRI contrast agent with activatable near-infrared (NIR) fluorescence imaging, aiming to simultaneously acquire comprehensive pathological features of RA from both structural and molecular imaging perspectives. Moreover, taking advantage of its targeting function to synovial microphages, hMnO2-IR@BSA-PEG-FA demonstrated a remarkable capability to accumulate effectively at the synovial tissue. Additionally, hMnO2 responded to the mild acidity and reactive oxygen species (ROS) in the RA microenvironment, leading to the controlled release of Mn2+ ions and IR780, which separately caused special MRI contrast enhancement of synovial tissues and sensitively demonstrated the presence of ROS and weakly acid microenvironment by NIR imaging. Consequently, hMnO2-IR@BSA-PEG-FA is expected to serve as a promising nanoplatform, offering valuable assistance in the precise diagnosis of early-stage RA by specially providing comprehensive information about the pathological features.

Effect of Docetaxel on Matrix Metalloproteinase 1 Expression in Freund’s Adjuvant Induced Arthritis

Rheumatoid arthritis is an autoimmune disorder that affects the synovial joints. It lead to inflammatory changes occur in synovial tissue, cartilage, bone, and, less frequently, extra-articular structures. Docetaxel, is an anti-neoplastic drug. Methotrexate is a treatment for early-stage rheumatoid arthritis but have 30% failure in treatment within the first year due to resistance or side effects. Matrix metalloproteinase 1 is the proteinase primarily in charge of the irreversible degradation of cartilage, bone, and tendons in the joints, which are induced by cytokines. This study aims to evaluate the effects of docetaxel and methotrexate on Matrix metalloproteinase 1 in the structure of the induced arthritis joints. Methods: To induce the disease, complete Freund's adjuvant is injected subcutaneously into rats. From the 40 male Wister rats, five groups of eight were formed. The control group is composed of non-diseased rats. The second group is induced by complete Freund's adjuvant and 0.5 ml of normal saline was administered intraperitoneally to both the control and induction groups. After being induced by complete Freund's adjuvant, the third group is administered 1 mg/kg/ on alternate day of Docetaxel based on a preliminary experiment. The fourth group is induced and given 1 mg/kg/week of Methotrexate intraperitoneally. The fifth group receives a half dose of Methotrexate and Docetaxel simultaneously. Serum level of Anti Cyclical citrullinated Peptide Antibody, tissue homogenate level of tumor necrosis factor-alpha, knee joint circumference and Immunohistochemical of Matrix metalloproteinase 1 measurements were applied. Results: Significant decreased in the Serum level of Anti-Cyclic citrullinated Peptide Antibody, tissue homogenate level of tumor necrosis factor-alpha & Knee joint circumference in the Docetaxel group. significant lowering in the expression of Matrix metalloproteinase 1 immunoreactivities in Docetaxel and Methotrexate groups with almost absent spots of positive reaction with the matrix of synovial tissue, hyaline cartilage & articular surface. Conclusion: This study showed that Docetaxel may have anti-arthritic effect through their significant lowering expression of Matrix metalloproteinase 1 immunoreactivities.
 

Bone disease imaging through the near-infrared-II window

Skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Optical imaging through the near-infrared-II window (NIR-II, 1000–1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can passively target the bone marrow, which can be effective for over two months. We therefore develop the high-resolution NIR-II imaging method for bone disease diagnosis, including the 3D bone imaging instrumentation to show the intravital bone morphology. We demonstrate the monitoring of 1 mm bone defects with spatial resolution comparable to the X-ray imaging result. Moreover, NIR-II imaging can reveal the early onset inflammation as the synovitis in the early stage of rheumatoid arthritis, comparable to micro computed tomography (μCT) in diagnosis of osteoarthritis, including the symptoms of osteophyte and hyperostosis in the knee joint.

Análisis de costo-efectividad del abordaje clínico en fase temprana vs. fase establecida en una cohorte de pacientes con artritis reumatoide de una institución prestadora de servicios de salud de cuarto nivel en Colombia

IntroductionRheumatoid arthritis (RA) is a high-cost disease, which allows patients to be classified into early or established phase approaches. ObjectiveThe purpose of this work was to perform a cost-effectiveness analysis comparing both phases with patient data at a 6-month time horizon from a third-party payer perspective. Materials and methodsThe population was delimited. The costs and effectiveness of each of the phases were estimated. A decision tree-type economic evaluation model was developed, and the Incremental Cost-Effectiveness Ratio (ICER) was calculated with the respective sensitivity analyses, both deterministic and probabilistic. ResultsIn terms of costs, it was found that for effectiveness in goals, the cost was 85% higher in the established than in the early phase. Similarly, for non-target effectiveness, the cost was 77% higher in the established than in the early phase. On the other hand, the effectiveness results were better in the early phase compared to the established phase. Regarding the ICER, it was determined that the early phase approach saves $2,326,389 COPcte (colombian pesos current currency) per patient in goals at 6 months of treatment, compared to the established phase approach. ConclusionThe clinical approach to early-stage rheumatoid arthritis is a less costly and more effective alternative vs. the established phase, as it generates savings for the third-party payer over a 6-month time horizon, from a third-party payer perspective.

OA17 Rheumatoid meningitis - a rare complication of rheumatoid arthritis

Abstract Introduction A wide spectrum of neurological complications can occur in rheumatoid arthritis (RA) including peripheral neuropathy, mononeuritis multiplex and rheumatoid vasculitis. Cerebrovascular disease is also common. We describe a rare neurological complication of RA. Case description The patient was first diagnosed with seropositive RA in 2015 at the age of 68. His rheumatoid factor at presentation was 144 kIU/L and CCP antibodies >340 U/mL. His background include alcohol excess and obstructive sleep apnoea with peripheral neuropathy attributed to alcohol. Nerve conduction studies demonstrated axonal neuropathy. By 2016, he had achieved good disease control with combination methotrexate and sulfasalazine. In 2018, he was admitted to stroke services with right arm weakness and focal neurological deficit on examination. An urgent CT head showed possible right parietal extra dural haemmorhage. His CRP was <5, ESR 24 with a normal ANA. Borrelia, syphilis and HIV screening were normal. Anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Hu, anti-Yo and anti-Ri antibodies were all negative. Lumbar puncture revealed a normal glucose and red blood cells count but the CSF protein was raised at 851 mg/L with a lymphocyte count of 9/ul. Gram stain, culture, viral PCR for HSV, VZV, enterovirus, parechovirus and adenovirus were normal and CSF cytology demonstrated a lymphocyte pleocytosis. Subsequent contrast MRI head scan showed leptomeningeal enhancement with gadolinium contrast. MRI of the cervical spine and brachial plexus was normal and an EMG/NCS of the upper limb demonstrated an incidental ulnar nerve compression at the elbow. Following neurology input, the leptomeningeal enhancement was thought to represent rheumatoid meningitis (RM). He was treated with 1 mg/kg prednisolone and rituximab with prompt and complete recovery. He remains well from both the perspective of his RA and RM. Discussion RM is a rare form of aseptic meningitis. Aseptic meningitis is commonly defined as clinical and CSF evidence of meningeal inflammation in the absence of an infectious aetiology. The vast differential includes malignancies, drug-induced and autoimmune diseases, for example lupus and sarcoidosis. The diagnosis of RM requires a high index of suspicion as well as exclusion of other causes. Historically RM was diagnosed at post-mortem but MRI scanning means pre-mortem diagnosis is possible. It is considered rare but serious manifestation of RA. Case reports suggest RM usually occurs in those with long standing seropositive RA but RM has been described in the early stages of RA and even as a presenting feature. Peripheral disease activity does not correlate with occurrence of RM. The clinical presentations vary depending on the brain structure involved and can include motor or sensory deficits, cognitive disturbance and seizures. It may mimic many other conditions. Radiological findings will not distinguish RM from other causes of aseptic meningitis. CSF finding of lymphocytosis and rheumatoid factor (if available) may help distinguish RM from other causes. Meningeal biopsy can confirm the diagnosis. Due to the rarity of RM, there are no current guidelines on treatment. Historically, corticosteroids are the main induction agent. There are case reports highlighting possible success from the addition of cyclophosphamide and rituximab. Case series also highlight a significant mortality rate in excess of 60% even despite treatment. This may represent publication and historical bias. Key learning points Rheumatoid meningitis (RM) is a rare but serious complication of rheumatoid arthritis. RM may not correlate with disease activity nor disease duration. Diagnosis is a challenge due to its wide clinical phenotype as well as the non-specificity of imaging, lumbar puncture and serological findings. Treatment options are based on case reports and series and include corticosteroids, rituximab and cyclophosphamide.

A deep registration method for accurate quantification of joint space narrowing progression in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that leads to progressive articular destruction and severe disability. Joint space narrowing (JSN) has been regarded as an important indicator for RA progression and has received significant attention. Radiology plays a crucial role in the diagnosis and monitoring of RA through the assessment of joint space. A new framework for monitoring joint space by quantifying joint space narrowing (JSN) progression through image registration in radiographic images has emerged as a promising research direction. This framework offers the advantage of high accuracy; however, challenges still exist in reducing mismatches and improving reliability. In this work, we utilize a deep intra-subject rigid registration network to automatically quantify JSN progression in the early stages of RA. In our experiments, the mean-square error of the Euclidean distance between the moving and fixed images was 0.0031, the standard deviation was 0.0661 mm and the mismatching rate was 0.48%. Our method achieves sub-pixel level accuracy, surpassing manual measurements significantly. The proposed method is robust to noise, rotation and scaling of joints. Moreover, it provides misalignment visualization, which can assist radiologists and rheumatologists in assessing the reliability of quantification, exhibiting potential for future clinical applications. As a result, we are optimistic that our proposed method will make a significant contribution to the automatic quantification of JSN progression in RA. Code is available at https://github.com/pokeblow/Deep-Registration-QJSN-Finger.git.

Peripheral blood lymphocytes apoptosis role in rheumatoid arthritis progressing

Rheumatoid arthritis (RA) is an autoimmune, chronic, and genetically linked inflammatory lesion of joint tissues that is accompanied by extra-articular systemic pathologies. The disease progression leads to joints immobilization, and eventually, the patient's disability occurs approximately ten years from the first clinical manifestation. RA pathogenesis involves various mechanisms: specific joint-related damage, nonspecific adaptive, and vessel-related pathological changes. Our research aimed to study the role of peripheral blood lymphocyte apoptosis in RA pathogenesis. We have analyzed research data from Google Scholar, PubMed, Web of Science, and Scopus databases to investigate the role of lymphocyte apoptosis in RA progression. Clinical manifestations in RA are caused by autoreactive T- and B-lymphocyte activity supported by humoral and cellular immune factors activity. Disease pathogenesis is caused by an imbalance in the process of programmed cell death (apoptosis): a proportion of immune cells are rapidly destroyed. In contrast, apoptosis is inhibited in the other classes of immune cells. High infiltration of the joint by autoreactive sensitized lymphocytes worsens the patient's condition. Apoptosis inhibition is especially noticeable in the early stages of RA and correlates with the concentration of the anti-apoptotic molecule Bcl-2 in the synovia. Activating the apoptotic destruction of lymphocytes (by drug action) allows a positive therapeutic effect and sustained remission. However, it should be noted that genetic factors play a significant role in the onset, progression and drug response of RA. In addition, environmental and behavioral factors can activate RA progression and influence treatment efficacy.

New pro-inflammatory cytokine IL-40 is produced by activated neutrophils and plays a role in the early stages of seropositive rheumatoid arthritis

ObjectiveInterleukin (IL)-40 is a new cytokine related to immune system function and malignancies. Recently, an association of IL-40 with rheumatoid arthritis (RA) and externalisation of neutrophil extracellular traps (NETosis) was...

OA05 Harnessing high throughput multiplex immunoassays and protein association networks to identify diagnostic protein biomarkers of rheumatoid arthritis-cardiovascular disease (RA-CVD) multimorbid axis

Abstract Background/Aims People with rheumatoid arthritis (RA) have higher mortality rates compared to the general population, primarily due to excess cardiovascular (CV) disease (CVD). The earliest stages of RA are associated with CV abnormalities but biomarkers to identify CVD in early RA are lacking. We aimed to identify focused protein biomarkers that associate with cardiac magnetic resonance imaging (CMR) abnormalities in a treatment-naïve, new-onset RA trial cohort and the predominant inflammatory and metabolic pathways involved in RA-CVD. Methods CADERA (Coronary Artery Disease in Early RA) was a bolt-on study to a parent RCT in an early RA inception cohort. 81 treatment-naïve early RA patients underwent CMR at baseline as part of CADERA. Proximity extension immunoassay (OIink) was used to measure normalised protein expression across inflammation, cardiovascular II/III and cardiometabolic panels in CADERA patients. Bayesian mixed effects linear regression was used to identify significant proteins associated with CMR parameters of myocardial oedema/fibrosis and vascular stiffness at baseline. Then, an expanded protein-protein interaction (PPI) network using above proteins was created using an induced network approach (String-DB) and k-means clustering applied to identify protein clusters that were subsequently subjected to Gene ontology (GO) and KEGG enrichment analysis. Results Of 340 proteins analysed using Olink, 108 proteins were associated with CMR markers of myocardial fibrosis/oedema (64 proteins) and vascular stiffness (44 proteins) Table 1 highlights the top 5 proteins for each CMR parameter. K-means clustering of the expanded PPI network identified 4 clusters with roles in vascular endothelial growth factor receptor binding and JAK-STAT signalling pathway (cluster 1); IL27 receptor binding and NF-kappa B signalling pathway (cluster 2); Macrophage CSF receptor binding and ErbB signalling pathway (cluster 3); and IL10 receptor activity and complement and coagulation cascades (cluster 4). Conclusion This is the first study to identify protein biomarkers of RA-CVD, an area of unmet clinical need, using a combination of targeted high throughput immunoassays, Bayesian and network analyses. Targeted techniques such as Olink may help identify potential diagnostic biomarkers of RA-CVD. Pathway analysis provides insight into the inter-relationship between inflammation and metabolic mediators of RA-CVD axis. Disclosure R. Shukla: None. N. Black: None. D. Plant: None. C. Miller: None. S. Plein: None. M.H. Buch: None.

P109 Personalised comprehensive care packages for people with rheumatoid arthritis: a survey-based study

Abstract Background/Aims Socioeconomic and clinical factors are closely associated with long-term disease outcomes in rheumatoid arthritis (RA). There is increasing evidence for holistic, targeted management of people with RA, including at first presentation. This study aimed to determine how people with, and those involved in the treatment of RA, benefit from personalised care packages and treatment programmes. Methods An online survey was developed by an expert panel comprising physicians, psychologists, epidemiologists and patients, following three multidisciplinary workshops which included patients. Questions were designed to evaluate participants’ views on multidisciplinary Team (MDT) involvement in the care of patients at early-stage RA and onwards. The online survey underwent extensive revisions by patients and clinicians, before dissemination to patients and healthcare professionals (HCPs) in the UK. Results We received 41 complete responses: 23 (57.5%) rheumatology consultants/trainees, seven (17.5%) rheumatology specialist nurses, five (12.5%) occupational therapists, three (7.5%) physiotherapists, one dietician (2.5%) and one patient (2.5%). 82.9% of respondents agreed that people with RA need access to the same “early” care package (comprising a core MDT) at time of diagnosis. On subsequent clinical reviews, 85.4% of respondents agreed that the care package for people with early RA may need to be tailored to an individual’s clinical, psychological and social needs. 58.5% of respondents confirmed that a standard core packaging with input from a consultant rheumatologist, clinical nurse specialist/patient educator, general practitioner and pharmacist is appropriate for patients with early RA, irrespective of patient or disease-related factors; 36.6% disagreed and 4.9% were unsure. Of those disagreeing with this statement, 36.7% agreed not all of these healthcare professionals are relevant to patient care at time of diagnosis, whilst 53.3% gave another reason and 10% were unsure. 68.3% of participants suggested additional involvement of 1-6 MDT members in patient care, specifically occupational therapists, physiotherapists and psychologists. Other posited that primary care may be included occasionally, and additional MDT members’ expertise in early disease may be overwhelming and require frequent review. There was strong agreement (median 10/10 on Likert scale) for the following two statements: ‘A care package with core members of the multidisciplinary rheumatology team need to be available to people newly diagnosed with RA’; ‘Personalised comprehensive care packages, comprising a core plus various additional members of the multidisciplinary team, need to be offered and adapted according to a person’s individual disease characteristics and socio-economic circumstances’. Conclusion HCPs caring for people with RA overwhelmingly agree with a tailored MDT involvement from an early stage of disease, reviewed regularly and adapted. Care packages need to be personalised to account for bio-psycho-social factors. HCPs need to acknowledge that the “ideal” care package may vary markedly between patients to maximise impact and benefit for patients. Disclosure M. Dey: None. A.D. Busby: None. H. Lempp: None. E. Nikiphorou: None.

Difficult-to-treat rheumatoid arthritis (D2T RA): clinical issues at early stages of disease

ObjectivesMost studies on difficult-to-treat rheumatoid arthritis (D2T RA) have focused on established RA. Here, we analyse whether disease activity in the early stages of RA could influence progression to a...

Nutrients and rheumatoid arthritis: From the perspective of neutrophils.

Neutrophils are considered as core immune cells involve in the early stage of rheumatoid arthritis (RA) and participate in the disease progression. The underlining mechanisms include the elevated chemotaxis and infiltration of neutrophils, the increase in the reactive oxygen species and the promotion of neutrophil extracellular traps formation. Accumulating studies demonstrated the important role of nutrients intake played in the initiation and progression of RA. This study summarized the effects of several macronutrients and micronutrients on regulating RA through the modulation of activated neutrophils and appealed for a healthy diet in RA-risk individuals as well as RA patients.

PH-Switched Near-Infrared Fluorescent Strategy for Ratiometric Detection of ONOO- in Lysosomes and Precise Imaging of Oxidative Stress in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is well-known as a kind of autoimmune disease, which brings unbearable pain to the patients by multiple organ complications besides arthritis. To date, RA can be hardly cured, but early diagnosis and standard treatment can relieve symptoms and pain. Therefore, an effective tool to assist the early diagnosis of RA deserves considerable attention. On account of the overexpressed ONOO- during the early stage of RA, a near-infrared (NIR) receptor, Lyso-Cy, is proposed in this work by linker chemistry to expand the conjugated rhodamine framework by cyanine groups. Contributed by the pH-sensitive spiral ring in rhodamine, receptor Lyso-Cy has been found to be workable in lysosomes specifically, which was confirmed by the pH-dependent spectra with a narrow responding region and a well-calculated pKa value of 5.81. We presented an excellent ratiometric sensing protocol for ONOO- in an acidic environment, which was also available for targeting ONOO- in lysosomes selectively. This innovative dual-targeting responsive design is expected to be promising for assisting RA diagnosis at an early stage with respect to the joint inflammatory model established in this work at the organism level.

Immune and mathematical procedures in early diagnosis of psoriatic and seronegative rheumatoid arthritis

Objectives. Improvement of early diagnosis of psoriatic arthritis based on clinical data, immunological and mathematical research methods. Material and methods. The study was carried out between 2019 and 2022 at the Rheumatology and Nephrology Discipline, in the arthrology and rheumatology departments of the Timofei Moşneaga Republican Clinical Hospital. To accomplish the tasks set out in the study, 110 patients were examined, including 55 patients with psoriatic arthritis (group I) and 55 patients with rheumatoid arthritis (group II). Results. The range with the highest probability of psoriatic arthritis for the instrumental index is between 0.54 and 1.86. Of the 55 patients with psoriatic arthritis in 95% of patients clinical, laboratory, immunological and instrumental indices were within the range of the highest probability of the disease, which indicates a fairly high reliability of the mathematical model. Conclusions. Immune disorders in the early stages of rheumatoid arthritis and psoriatic arthritis are nonspecific and are characterized by an increase in CD16+ (26.2±1.5) and CD29+ (24.8±2.1) in rheumatoid arthritis, which is significantly higher than in psoriatic arthritis CD16+ (22.0±1.3) and CD29+ (17.4±3.2) (p <0.05). A mathematical model of rheumatoid arthritis and psoriatic arthritis has been developed, which serves as an additional way of diagnosing rheumatoid arthritis and early psoriatic arthritis. Keywords: rheumatoid, psoriatic arthritis, mathematical, immune diagnosis.

Mitochondria as disease-relevant organelles in rheumatoid arthritis.

Mitochondria are the controllers of cell metabolism and are recognized as decision makers in cell death pathways, organizers of cytoplasmic signaling networks, managers of cellular stress responses, and regulators of nuclear gene expression. Cells of the immune system are particularly dependent on mitochondrial resources, as they must swiftly respond to danger signals with activation, trafficking, migration, and generation of daughter cells. Analogously, faulty immune responses that lead to autoimmunity and tissue inflammation rely on mitochondria to supply energy, cell building blocks and metabolic intermediates. Emerging data endorse the concept that mitochondrial fitness, and the lack of it, is of particular relevance in the autoimmune disease rheumatoid arthritis (RA) where deviations of bioenergetic and biosynthetic flux affect T cells during early and late stages of disease. During early stages of RA, mitochondrial deficiency allows naïve RA T cells to lose self-tolerance, biasing fundamental choices of the immune system toward immune-mediated tissue damage and away from host protection. During late stages of RA, mitochondrial abnormalities shape the response patterns of RA effector T cells engaged in the inflammatory lesions, enabling chronicity of tissue damage and tissue remodeling. In the inflamed joint, autoreactive T cells partner with metabolically reprogrammed tissue macrophages that specialize in antigen-presentation and survive by adapting to the glucose-deplete tissue microenvironment. Here, we summarize recent data on dysfunctional mitochondria and mitochondria-derived signals relevant in the RA disease process that offer novel opportunities to deter autoimmune tissue inflammation by metabolic interference.

Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis.

Muscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA. This cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index > 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching). In total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P < 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P > 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P < 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P < 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138-2.132)], and myopenia [AOR 2.983, 95% CI (1.192-7.465)] was independently associated with physical dysfunction in the patients with early RA. Our data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.

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.