Rheumatoid Arthritis Research Articles

Macrophage corpses for immunoregulation and targeted drug delivery in treatment of collagen-induced arthritis mice

The role of pro-inflammatory macrophages (M1) in rheumatoid arthritis (RA) is significant, as they produce excessive cytokines. Targeting efferocytosis is a potential manner to repolarize M1 macrophages into pro-resolving M2 phenotype, which restores immune homeostasis by releasing anti-inflammatory mediators. In this study, liquid nitrogen-treated dead macrophages (DM) are employed to act as a dead cell-derived active targeted drug carrier for shikonin (SHK) and induce efferocytosis in M1 macrophages with the enhancement of SHK as an AMP-activated protein kinase (AMPK)-activator. The synergistic activation of AMPK leads to uncoupled protein 2 (UCP2) upregulation and reprograms M1 macrophages into M2 phenotypes by promoting oxidative phosphorylation. In the mouse model of collagen-induced arthritis, the intravenous administration of DM/SHK leads to a consistent transformation of M1 macrophages into the M2 phenotype within the infiltrative synovium. This transformation of macrophages results in the restoration of immune homeostasis in the synovium through an increase in the production of pro-resolving mediators. Additionally, it inhibits synovial proliferation and infiltration and provides protection against erosion of cartilage and bone. In summary, LNT-based DM serves as an active targeting drug carrier to M1 macrophages and also acts synergistically with SHK to target immunometabolism.

Evaluation of Drug Effects on IL-17 and TNF levels in Patients with Rheumatoid Arthritis

Evaluation of Drug Effects on IL-17 and TNF levels in Patients with Rheumatoid Arthritis

Aberrant overexpression of the autoantigen protein vimentin promotes Th17 cell differentiation and autoimmune arthritis via activation of STAT3 signaling

Vimentin contributes to the positioning and function of organelles, cell migration, adhesion, and division. However, secreted vimentin accumulates on the cell surface (Mor-Vaknin et al., 2003; Ramos et al., 2020 [1,2]) where it acts as a coreceptor for viral infection and as an autoantigen in inflammatory and autoimmune diseases. The roles of vimentin in Th17 cells were examined in mice with knockdown of vimentin. We also examined whether STAT3 is required for vimentin expression.Vimentin expression was significantly increased in Th17 cells through STAT3 activation, and vimentin+ IL-17+ T cells were markedly increased in the joint and spleen tissues of CIA mice. The arthritis score and expression levels of proinflammatory cytokines were significantly decreased in CIA mice treated with vimentin shRNA vector.In this study, we demonstrated that vimentin is significantly expressed in Th17 cells through STAT3 activation. Our results provide new insights into the role of vimentin in Th17 cells and the complex pathogenesis of RA.

The Therapeutic Efficacy of Abatacept for Rheumatoid Arthritis-Associated Interstitial Lung Disease: Insights from a 12-Month Trial Using Semi-Quantitative Chest High-Resolution Computed Tomography Imaging.

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major complication of rheumatoid arthritis (RA), but effective treatment remains an unmet need in its management. Our aim was to evaluate the therapeutic efficacy of abatacept for RA-ILD. Methods: This observational retrospective study included patients with RA-ILD treated with abatacept between 2012 and 2021. Indices of RA disease activity and interstitial lung disease (Disease Activity Score in 28 joints using C-reactive Protein [DAS28-CRP], Simplified Disease Activity Index [SDAI], Clinical Disease Activity Index [CDAI], serum Krebs von den Lungen-6 levels, % forced vital capacity [%FVC], and semi-quantified chest high-resolution computed tomography scores) were evaluated before and 1 year after the start of abatacept administration. Results: Overall, 38 patients were included. DAS28-CRP, SDAI, and CDAI were significantly improved (all with p < 0.0001). Total ground-glass opacity scores were decreased in both patients with usual interstitial pneumonia (UIP)-like patterns and with non-UIP-like patterns (p = 0.008 and <0.002, respectively). Total fibrosis scores were also decreased in the UIP-like pattern group (p < 0.042). The %FVC remained stable. Conclusions: Abatacept significantly improves RA disease activity and reduces pulmonary inflammation in patients with RA-ILD.

Serum selenium, selenoprotein P and glutathione peroxidase 3 in rheumatoid, psoriatic, juvenile idiopathic arthritis, and osteoarthritis

IntroductionSelenoprotein P (SELENOP) controls selenium transport, and glutathione peroxidase 3 (GPx3) elicits antioxidant activity in blood. Inflammation associates with Se deficiency, but knowledge concerning selenoproteins in inflammatory rheumatic musculoskeletal diseases (iRMD) is limited. We compared three Se biomarkers in patients with rheumatoid (RA), psoriatic (PsA), and juvenile idiopathic arthritis (JIA) in comparison to osteoarthritis (OA) and healthy subjects, to improve the data base on selenoprotein expression in iRMD. MethodsThe cross-sectional study enrolled n=272 patients with RA (n=131), PsA (n=67), JIA (n=22) and OA (n=52). Serum Se was quantified by total reflection X-ray fluorescence, SELENOP by ELISA and GPx3 by an enzymatic test. Data from the EPIC trial served as reference. Impairment of daily life was assessed by the Functional Ability Questionnaire (FfbH). ResultsSerum SELENOP and Se concentrations correlated linearly in all groups and were below the average measured in EPIC. Se concentration was not different between the patient groups. Compared to controls, SELENOP levels were low in iRMD patients. GPx3 activity was particularly low in JIA and PsA. Seropositive but not seronegative RA patients displayed a disrupted interaction between GPx3 and Se or SELENOP. SELENOP associated with the functional status measured by the FfbH, most pronounced in OA (R=0.76, p<0.01). DiscussionThe data indicate selenoprotein deficiency in the majority of patients with iRMD, and a positive relation of SELENOP with functional status in OA. Since increased Se supply improves selenoprotein biosynthesis, a personalized correction of diagnosed deficiency merits consideration to improve Se transport and ameliorate disease burden.

Proximod as a potential therapy for rheumatoid arthritis

Proximod as a potential therapy for rheumatoid arthritis

Long-term outcomes and trends in elbow arthroplasty with Coonrad-Morrey prosthesis: a retrospective study in large group of patients.

Total Elbow Arthroplasty (TEA) was first developed to treat severe rheumatoid arthritis, but its uses have grown to encompass end-stage osteoarthritis, post-traumatic arthritis, and distal humeral fractures. This study analyzes indications changes, long-term survival, complications, and post-operative functional results of the Coonrad-Morrey prostheses, enhancing the existing literature on this technique and substantial case history. We included 122 arthroplasties in 117 patients, 28 males and 89 females (mean age of 67 years) treated in our hospital between 2002 and 2016. Minimum follow-up was four years. We collect functional parameters of 48 patients (51 elbows), due to death of patients due to old age and loss at follow-up. Survival rate at five years was 90%, 85% at 10 years and 83% at 15 years. The overall medium Mayo elbow score was 79.7 ± 18.3 with the highest result in osteoarthritis patients (p < 0.005); QuickDASH score was 33.1 ± 25.5 with the worse result in rheumatoid group. Average post-operative arc of motion (ROM) was 95°±27°. There were complications in 46 out of 122 cases (37.7%) and revision surgeries were performed in 12 of them (9.8%): seven aseptic loosening, four late septic loosening, one bushing wear. In 27 instances (22.1%) was reported ulnar nerve involvement. Coonrad-Morrey prosthesis has shown satisfactory clinical results in the treatment of a wide range of pathologies. The long-term implant survivorship was satisfactory, yet the occurrence of failures and complications cannot be overlooked, above all the ulnar nerve paresthesia. There was a good recovery in quality of life, pain-free with limited residual limb disability.

Indirect costs assessment and intangible costs description of rheumatoid arthritis patients with biological therapy in Morocco: ECORAM Study.

The aims of study are to estimate the indirect costs and intangible costs of RA in Morocco and to identify the factors likely to influence these costs among suffering patients. In the current study, data were collected by face-to-face interviews using a questionnaire in addition to the patient's files. Indirect costs including productivity losses and formal care, and intangible costs such as the cessation of physical and leisure activities, family care and divorce or remaining single until menopause's age for women due to the disease were reported for 110 RA patients. The results show that among patients who lost totally or partially their salary, the annual average costs is $2337.73 ± 1649.80 per patient, with a minimum and a maximum of $600 and $9630 respectively. As regards formal care, only 13 patients reported that they paid for care services; the annual average cost was $421.84 ± 261.34 with a minimum of $252 and a maximum of $1200. Statistical analysis revealed significant differences between annual lost salary and gender (p = .04) disease duration (p = .016) and sport/leisure activities cessation (p = .08). Besides the burden in terms of productivity loss and caregivers' costs, the intangible costs are considerable, especially those related to divorce and spinsterhood. These conclusions may contribute to the understanding of the socio-economic impact of the disease and to the development of strategies for better governance of RA in Morocco.

Homeostatic signals, including IL-7 and self-MHC recognition, induce the development of peripheral helper T cells, which are enriched in the joints of rheumatoid arthritis

Homeostatic signals, including IL-7 and self-MHC recognition, induce the development of peripheral helper T cells, which are enriched in the joints of rheumatoid arthritis

Columbianadin ameliorates rheumatoid arthritis by attenuating synoviocyte hyperplasia through targeted vimentin to inhibit the VAV2/Rac-1 signaling pathway

IntroductionRheumatoid arthritis (RA) is an autoimmune disease pathologically characterized by synovial inflammation. The abnormal activation of synoviocytes seems to accompany the progression of RA. The role and exact molecular mechanism in RA of columbianadin (CBN) which is a natural coumarin is still unclear. ObjectivesThe present research aimed to investigate the effect of vimentin on the abnormal growth characteristics of RA synoviocytes and the targeted regulatory role of CBN. MethodsCell migration and invasion were detected using the wound healing and transwell method. Mechanistically, the direct molecular targets of CBN were screened and identified by activity-based protein profiling. The expression of relevant proteins and mRNA in cells and mouse synovium was detected by western blotting and qRT-PCR. Changes in the degree of paw swelling and body weight of mice were recorded. H&E staining, toluidine blue staining, and micro-CT were used to visualize the degree of pathological damage in the ankle joints of mice. Small interfering RNA and plasmid overexpression of vimentin were used to observe their effects on MH7A cell proliferation, migration, apoptosis, and downstream molecular signaling. ResultsThe TNF-α-induced proliferation and migration of MH7A cells could be significantly repressed by CBN (25,50 μM), and the expression of apoptosis and autophagy-associated proteins could be modulated. Furthermore, CBN could directly bind to vimentin and inhibit its expression and function in synoviocytes, thereby ameliorating foot and paw swelling and joint damage in CIA mice. Silencing and overexpression of vimentin might be involved in developing RA synovial hyperplasia and invasive cartilage by activating VAV2 phosphorylation-mediated expression of Rac-1, which affects abnormal growth characteristics, such as synoviocyte invasion and migration. ConclusionCBN-targeted vimentin restrains the overactivation of RA synoviocytes thereby delaying the pathological process in CIA mice, which provides valuable targets and insights for understanding the pathological mechanisms of RA synovial hyperplasia.

A Case of Secondary Membranous Nephropathy Caused by Rheumatoid Arthritis Accompanied by Double Positive for Anti-GBM Antibodies and Proteinase 3 (PR3)-ANCA

A Case of Secondary Membranous Nephropathy Caused by Rheumatoid Arthritis Accompanied by Double Positive for Anti-GBM Antibodies and Proteinase 3 (PR3)-ANCA

ID: 335853 Initial Clinical Safety and Feasibility from RESET-RA Study: Novel Neuroimmune Modulation Device for Rheumatoid Arthritis

ID: 335853 Initial Clinical Safety and Feasibility from RESET-RA Study: Novel Neuroimmune Modulation Device for Rheumatoid Arthritis

Oral Bioefficacy Enhancement of Capsaicin for the Effective Treatment of Rheumatoid Arthritis

Oral Bioefficacy Enhancement of Capsaicin for the Effective Treatment of Rheumatoid Arthritis

Licorice-regulated gut–joint axis for alleviating collagen-induced rheumatoid arthritis

Licorice-regulated gut–joint axis for alleviating collagen-induced rheumatoid arthritis

Fatal outcome in isolated Pauci-immune pulmonary capillaritis: A case report.

Isolated Pauci-immune pulmonary capillaritis (IPIPC) is a rare form of small vessel vasculitis that affects only the lungs, causing inflammation of pulmonary capillaries and potentially leading to severe outcomes like alveolar haemorrhage. A 23-year-old woman with a prior diagnosis of rheumatoid arthritis presented with hemoptysis and respiratory distress, ultimately diagnosed with IPIPC. Despite treatment with high-dose steroids and intravenous immunoglobulin, her condition deteriorated, resulting in respiratory failure and death. IPIPC often lacks systemic symptoms and ANCA positivity, complicating diagnosis and treatment. Imaging, bronchoscopy, and histopathology are key for diagnosis, while management typically involves corticosteroids and possibly immunosuppressives. The case underscores the challenges in identifying and treating IPIPC, highlighting the importance of early intervention to improve prognosis, even though complications can still lead to significant respiratory issues and mortality.

Natural synergy: Oleanolic acid-curcumin co-assembled nanoparticles combat osteoarthritis

Curcumin (Cur) is a natural polyphenol that is one of the most valuable natural products. However, its use as a functional food is limited by low water solubility, chemical instability and poor bioavailability. In this study, a supramolecular co-assembly strategy was used to construct an oleanolic acid-curcumin (OLA-Cur) co-assembly composite nano-slow-release treatment system. As a co-assembled compound, OLA is a widely present pentacyclic triterpenoid compound with multiple biological activities in the plant kingdom, which is expected to jointly alleviate the damaging effects of papain-induced mouse osteoarthritis model. The OLA-Cur NPs shows the solid core-shell structure, which can effectively improve the water solubility of Cur and OLA, and has good stability and sustained release characteristics. The analysis results show that the two compounds are mainly assembled through hydrogen bonding interactions, hydrophobic interactions, and π - π stacking interactions. The OLA-Cur NPs can inhibit the release of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β induced by LPS in RAW264.7 mouse macrophages, promote the secretion of anti-inflammatory cytokine IL-10, and improve the oxidative stress index of hydrogen peroxide induced human rheumatoid arthritis synovial fibroblasts. In addition, it has a certain improvement effect on cartilage and subchondral bone damage in mouse osteoarthritis models. These findings suggest that constructing co-assembled composite nanoparticles based on pure natural compounds may break through the limitations of a variety of important nutritional ingredients in functional foods.

Response to Research Trends of Rheumatoid Arthritis and Depression [Letter]

Response to Research Trends of Rheumatoid Arthritis and Depression [Letter]

Rapid Characterization of the Potential Active of Sinomenine in Rats by Ultra-High-Performance Liquid Chromatography-Quadrupole-Exactive Orbitrap Mass Spectrometry and Molecular Docking.

Sinomenium acutum (Thunb.) Rehd. et Wils is widely used in the treatment of rheumatoid arthritis, with its alkaloid compound sinomenine (SIN) being renowned for its significant anti-inflammatory properties. However, despite its widespread application, the in vivo anti-inflammatory mechanisms and metabolic pathways of SIN remain incompletely understood. This study established a rapid and reliable method based on an ultra-high-performance liquid chromatography method coupled with Quadrupole-Exactive Orbitrap mass spectrometry and molecular docking to identify and characterize SIN and 69 metabolites in rat plasma, urine, and feces, revealing primary metabolic pathways of hydroxylation, demethylation, sulfation, and glucuronidation. Molecular docking results revealed that phase I reactions, including dedimethylation, demethylation, dehydrogenation, and dihydroxylation, along with their composite reactions, were pivotal in influencing SIN's in vivo anti-inflammatory activity. M28, M36, and M59 are potentially the most anti-inflammatory active metabolites of SIN in vivo. This comprehensive analysis unveils SIN's metabolic pathways, offering insights into its biological processes and suggesting a novel approach for exploring active drug constituents. These findings pave the way for further understanding SIN's anti-inflammatory mechanisms, contributing significantly to the development of new therapeutic strategies.

"Seropositive Rheumatoid Arthritis With Axial Skeleton Involvement In A 17-year-old Female Athlete."

"Seropositive Rheumatoid Arthritis With Axial Skeleton Involvement In A 17-year-old Female Athlete."

Clinical correlates of lifetime and current comorbidity patterns in autoimmune and inflammatory diseases

BackgroundAutoimmune and inflammatory diseases (AIDs) are a heterogeneous group of disorders with diverse etiopathogenic mechanisms. This study explores the potential utility of family history, together with present and past comorbidities, in identifying distinct etiopathogenic subgroups. This approach may facilitate more accurate diagnosis, prognosis and personalized therapy. MethodsWe performed a multiple correspondence analysis on patients' comorbidities, followed by hierarchical principal component clustering of clinical data from 48 healthy volunteers and 327 patients with at least one of 19 selected AIDs included in the TRANSIMMUNOM cross-sectional study. ResultsWe identified three distinct clusters characterized by: 1) the absence of comorbidities, 2) polyautoimmunity, and 3) polyinflammation. These clusters were further distinguished by specific comorbidities and biological parameters. Autoantibodies, allergies, and viral infections characterized the polyautoimmunity cluster, while older age, BMI, depression, cancer, hypertension, periodontal disease, and dyslipidemia characterized the polyinflammation cluster. Rheumatoid arthritis patients were distributed across all three clusters. They had higher DAS28 and prevalence of extra-articular manifestations when belonging to the polyinflammation and polyautoimmunity clusters, and also lower ACPA and RF seropositivity and higher pain scores within the polyinflammation cluster. We developed a model allowing to classify AID patients into comorbidity clusters. ConclusionsIn this study, we have uncovered three distinct comorbidity profiles among AID patients. These profiles suggest the presence of distinct etiopathogenic mechanisms underlying these subgroups. Validation, longitudinal stability assessment, and exploration of their impact on therapy efficacy are needed for a comprehensive understanding of their potential role in personalized medicine.