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ID PMID Title PublicationDate abstract
32547141 Identification of Hub Genes in Type 2 Diabetes Mellitus Using Bioinformatics Analysis. 2020 BACKGROUND: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in the world with complicated pathogenesis. This study aimed to identify differentially expressed genes (DEGs) and molecular pathways in T2DM using bioinformatics analysis. MATERIALS AND METHODS: To explore potential therapeutic targets for T2DM, we analyzed three microarray datasets (GSE50397, GSE38642, and GSE44035) acquired from the Gene Expression Omnibus (GEO) database. DEGs between T2DM islet and normal islet were picked out by the GEO2R tool and Venn diagram software. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to identify the pathways and functional annotation of DEGs. Then, protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). RESULTS: In total, we identified 36 DEGs in the three datasets, including 32 up-regulated genes and four down-regulated genes. The improved functions and pathways of the DEGs enriched in cytokine-cytokine receptor interaction, pathways in cancer, PI3K-Akt signaling pathway, and Rheumatoid arthritis. Among them, ten hub genes with a high degree of connectivity were selected. Furthermore, via the re-analysis of DAVID, four genes (IL6, MMP3, MMP1, and IL11) were significantly enriched in the Rheumatoid arthritis pathway. CONCLUSION: Our study, based on the GEO database, identified four significant up-regulated DEGs and provided novel targets for diagnosis and treatment of T2DM.
31132976 An in silico Workflow that Yields Experimentally Comparable Inhibitors for Human Dihydroor 2020 INTRODUCTION: Rheumatoid Arthritis [RA] is an autoimmune disease that can cause chronic inflammation of the joints. Human DiHydroOrotate DeHydrogenase [DHODH] is a clinically validated drug target for the treatment of Rheumatoid Arthritis. DHODH inhibition results in beneficial immunosuppressant and anti-proliferative effects. MATERIALS AND METHODS: Leflunomide [LEF] and Brequinar Sodium [BREQ], drugs used in the treatment of RA, suppresses the immune cells responsible for inflammation but has several side-effects, most predominant being symptomatic liver damage and toxicity. An existing scaffold based on structural analogies with LEF and BREQ was used to screen out potent inhibitors of DHODH, in ZINC Database using 2D binary fingerprint. 10 structures similar to the scaffold were shortlisted due to their Tanimoto similarity coefficient. Selected structures were docked using the tools AutoDock, Ligand fit and iGEMDOCK with target human DHODH. High scoring compounds having similar interactions as that of scaffold were checked to evaluate their Drug-Likeliness. RESULTS: The five shortlisted compounds were then subjected to Molecular Dynamics Simulation studies for 50ns using GROMACS. Measures of structural similarity based on 2D Fingerprint Screening and Molecular Dynamics Simulation studies can suggest good leads for drug designing. The novelty of this study is that the workflow used here yields the same results that are at par with the experimental data. CONCLUSION: This suggests the use of the 2D fingerprint similarity search in various databases, followed by multiple docking algorithms and dynamics as a workflow that will lead to finding novel compounds that a structurally and functionally similar to LEF and BREQ.
33051991 Finite element method for nerve root decompression in minimally invasive endoscopic spinal 2021 Jul INTRODUCTION: Diagnosis is the key to improving spinal surgery outcomes. Improvements in the diagnosis of radiculopathy have created new indications for full-endoscopic spine surgery. We assessed the finite element method (FEM) to visualize and digitize lesions not detected by conventional diagnostic imaging. METHODS: We used FEM in two patients: a lumbar patient and a cervical patient. The lumbar patient was a 67-year-old woman with a history of rheumatoid arthritis; she also had osteoporosis and pulmonary fibrosis. She had left L3 radiculopathy due to an L3 vertebral fracture. The cervical patient was a 61-year-old woman with left C6 radiculopathy due to C5-C6 disc herniation. We performed full endoscopic foraminotomy per the patients's request. Based on preoperative and postoperative CT Digital Imaging and Communications in Medicine data of 0.5-mm slices, 3-D imaging data were reproduced, and kinetic simulation of FEM was performed. RESULTS: Postoperatively, both patients' radiculopathy disappeared, improving their activities of daily living and enabling them to walk and work. Also, the total contact area and maximum contact pressure of the nerve tissue decreased from 30% to 80% and from 33% to 67%, respectively. CONCLUSIONS: A new method for perioperative evaluation and simulation, FEM can be to visualize and digitize the conditions of the lesion causing radiculopathy. FEM that can overcome both time and economic constraints in routine clinical practice is needed.
31782724 Does biologic survival depend on co-prescribed methotrexate dose in established rheumatoid 2020 Jan OBJECTIVE: Several seminal studies have suggested that a combination therapy of biologics with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) improve disease outcomes in rheumatoid arthritis (RA). Hence, most guidelines reflect this practice. It has also been shown that methotrexate (MTX) at a dose of 8-10 mg/week is perhaps sufficient to achieve better outcomes in early RA. However, it is not clear whether this strategy enhances biologic retention in the patients with established RA. We present a real-world retrospective study to investigate whether csDMARD co-prescription improves biologic retention and the optimal dose to preserve such response. MATERIALS AND METHODS: All patients prescribed biologic therapy for RA at our center between 2003 and 2017 were identified through the departmental database. They were split into five groups based on a weekly MTX dose (≤7.5 mg, 10-17.5 mg, ≥20 mg), other csDMARD prescription, or biologic monotherapy. The one-way analysis of variance model for independent values was utilized to ascertain the significance of data. The Mann-Whitney two-tailed U test was employed to determine the significance of relationship between the monotherapy group and other arms. The significance level was predefined at 0.05. RESULTS: A total of 168 patients with 198 biologic events were included. The mean age was 59.4 years (range, 24-90 years). 78% were women. The mean disease duration was 155.6 months (range, 15-491). There was a statistically significant difference (p=0.03) in biologic retention among the five arms. Compared to monotherapy, the data remained significant for ≥20 mg MTX and csDMARD groups; however, the biologic retention in the other two MTX arms was not significant. There was no significant relationship among groups for DAS28 improvement (p=0.24). CONCLUSION: Our results suggest that to improve biologic retention, the MTX dose should be increased to 20 mg a week or more, and, in people with MTX intolerance, csDMARDs co-presciption can be an alternative strategy. Maintenance with a low-to-moderate MTX dose can lead to poorer retention rates.
33191284 Concerns, Healthcare Use, and Treatment Interruptions in Patients With Common Autoimmune R 2021 Apr OBJECTIVE: To assess concerns and healthcare-related behaviors of patients with autoimmune rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Adults from the United States with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) from the ArthritisPower Patient-Powered Research Network and CreakyJoints patient community completed surveys. Concerns and behaviors were compared among patients with different autoimmune conditions, disease-modifying antirheumatic drug (DMARD) use, and geographic measures of urban status, income, education, and COVID-19 activity. RESULTS: Among 1517 participants (925 RA, 299 PsA, 185 AS, 108 SLE), mean age was 55.1 years, 88.3% were female, and 89.5% were White. COVID-19 concerns were similar across the country and were higher in biologic users (P < 0.001). Avoidance of doctor's office visits (56.6%) or laboratory testing (42.3%) and use of telehealth (29.5%) were more common in urban areas. Among participants receiving a DMARD without COVID-19 or other respiratory illness, 14.9% stopped a DMARD, with 78.7% of DMARD interruptions not recommended by a physician. DMARD stopping was more common in participants with lower socioeconomic status (SES) and in participants who avoided an office visit (OR 1.46, 95% CI 1.04-2.04) or reported lack of telehealth availability OR 2.26 (95% CI 1.25-4.08). CONCLUSION: In the early months of the COVID-19 pandemic, patients with RA, PsA, AS, and SLE frequently avoided office visits and laboratory testing. DMARD interruptions commonly occurred without the advice of a physician and were associated with SES, office visits, and telehealth availability, highlighting the need for adequate healthcare access and attention to vulnerable populations during the pandemic.
32043729 Antiarthritic effect of chitosan nanoparticle loaded with embelin against adjuvant-induced 2020 May BACKGROUND: Rheumatoid arthritis (RA) is associated with joint damage. Effectiveness of embelin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism, and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable embelin-loaded chitosan nanoparticles (CS-embelin NPs) for the treatment of RA. METHODS: The rats were made arthritic using a subcutaneous injection with 0.1 ml complete Freund's adjuvant (CFA) into the footpad of the left hind paw. CS-embelin NPs (25 and 50 mg/kg) was administered from day 15 to day 28 after adjuvant injection. After the experimental period, the animals were sacrificed and various biochemical markers were assessed. RESULTS: Arthritic score and paw swelling were significantly reduced after treatment with CS-embelin NPs. Arthritis-induced rats showed a significant increase in malondialdehyde (MDA) and nitric oxide (NO) with a concomitant reduction of antioxidants in the paw tissue. CS-embelin NPs (25 and 50 mg/kg) reduced MDA and NO levels and restored antioxidant levels to normalcy by mitigating oxidative stress. The arthritic rats exhibited elevated tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1beta (IL-1β) serum concentrations, upregulated TNF- α and IL-6 protein levels and upregulated nuclear factor-kB (NF-kB) mRNA expression in paw tissues. Treatment with CS-embelin NPs (25 and 50 mg/kg) significantly reduced serum levels and down-regulated inflammatory markers to normalcy, dose-dependently. CONCLUSION: The results suggest that CS-embelin NPs displayed a protective effect against adjuvant-induced arthritis in rats mediated through antioxidant and anti-inflammatory effects.
32531094 Risk of connective tissue disease, morphoea and systemic vasculitis in patients with hidra 2021 Jan BACKGROUND: Hidradenitis suppurativa (HS) has been associated with auto-inflammatory conditions, yet the risk of developing connective tissue disease (CTD), morphoea and systemic vasculitis has not been well-characterized. OBJECTIVES: We sought to evaluate the risk of developing CTD, morphoea and systemic vasculitis in patients with HS. METHODS: Using claims data, we identified patients with HS and used 2 : 1 risk-set sampling to identify patients without HS. Patients with existing CTD were excluded. Patient follow-up lasted until first occurrence of the following events: the occurrence of outcome (i.e. systemic lupus erythematosus, morphoea, systemic sclerosis, Sjogren's Syndrome and systemic vasculitis), death, disenrolment or end of data stream. Hazard ratios (HR) of developing CTD, morphoea and systemic vasculitis were computed after 1 : 1 propensity score (PS) matching. RESULTS: After 2 : 1 risk-set sampling, we identified 78 122 HS patients and 156 247 non-HS comparators. The mean follow-up was 540 days. After PS matching, HS patients had an increased risk of systemic lupus erythematosus HR = 1.63 (1.31-2.03) and morphoea HR = 2.02 (1.32-3.11), compared to non-HS patients. We did not observe an increased risk for systemic sclerosis HR = 0.90 (0.59-1.44), Sjogren's Syndrome HR = 0.91 (0.73-1.14) or systemic vasculitis HR = 0.87 (0.64-1.20). CONCLUSION: In this population-based study, we observed an increased risk of developing systemic lupus erythematous and morphoea subsequent to a first-recorded diagnosis of hidradenitis suppurativa.
31994484 Salivary gland ultrasound integrated with 2016 ACR/EULAR classification criteria improves 2020 Mar OBJECTIVES: To evaluate the utility of salivary gland ultrasound (SGUS) in the diagnosis of primary Sjögren's syndrome (pSS) singly or integrated with 2016 ACR/EULAR classification criteria. METHODS: Patients with suspected pSS were enrolled in the study. SGUS semi-quantitative scoring was used to assess salivary gland. Clinical characteristics were recorded, including autoantibodies, ophthalmic tests, salivary glands scintigraphy (SGS) and labial biopsy. The diagnostic accuracy of SGUS score and complementary value of SGUS to 2016 ACR/EULAR criteria were analysed. RESULTS: 282 patients were included for analysis. 161 were diagnosed as pSS and 121 as non-SS. SGUS score≥5 showed 64.7% sensitivity and 81.4% specificity for the diagnosis of pSS. Positive anti-SSA, abnormal SGS and SGUS score were significantly higher in pSS than non-SS group (80.1% vs. 14.0%, p<0.01; 91.3% vs. 57.0%, p<0.01; 8.4±6.6 vs. 2.6±3.2, p<0.01 respectively). A weighted score [(anti-SSA×16.5) + (SGS×14.5) + (SGUS×4.5)] was constructed. The score ≥17.5 could improve the sensitivity, and almost keep the specificity comparing to 2016 ACR/EULAR criteria (89.9% vs. 85.6% and 79.5% vs. 82.2%). When replacing labial biopsy by SGUS in 2016 ACR/EULAR criteria, both sensitivity and specificity were a bit decreased (85.0% vs. 85.6% and 79.8% vs. 82.2%). When adding SGUS to 2016 ACR/EULAR criteria, it showed better performance by improving the sensitivity (90.8% vs. 85.6%), while not losing the specificity (83.7% vs. 82.2%). CONCLUSIONS: Adding SGUS score to the 2016 ACR/EULAR criteria can improve the diagnosis utility of pSS. SGUS may be a feasible and prospective tool in the diagnosis of pSS.
31856365 Is the taste acuity affected by oral dryness in primary Sjögren's syndrome patients? 2020 Apr OBJECTIVES: Taste disturbance is a symptom of primary Sjögren's syndrome (pSS) of unknown aetiology. This study's objectives were (a) to compare taste function in pSS vs. healthy subjects; (b) to establish whether there is an association between the taste acuity and oral dryness and/or the neurosensory threshold; and (c) to assess the impact of taste dysfunction on the quality of life (QoL). METHODOLOGY: This study was conducted on 65 pSS females and 62 healthy volunteers. The gustatory function was tested with taste strips test. Visual analogue scale was used for self-assessment of taste function. The electrogustometer was used to assess the neurosensory threshold. The oral dryness was assessed by the Clinical Oral Dryness Score, salivary flow rate and Xerostomia Inventory. The general and oral health-related QoL and mental health well-being were assessed using validated questionnaires. RESULTS: The pSS group had significantly impaired taste function, but this was not correlated with oral dryness. There was an association between taste acuity and the neurosensory threshold (β = -0.5, 95% CI = -0.2 to -0.1). The QoL was not impacted by taste dysfunction (p > .5). CONCLUSION: The results suggest that taste impairment in pSS is associated with neurosensory dysfunction and is unlikely to be due to oral dryness.
31254454 Incorporation of Salivary Gland Ultrasonography Into the American College of Rheumatology/ 2020 Apr OBJECTIVE: To assess whether the addition of salivary gland ultrasonography (SGUS) or replacement of current criteria items by SGUS influences the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for primary Sjögren's syndrome. METHODS: Included were consecutive patients with complete data on all ACR/EULAR items (n = 243) who underwent SGUS in our primary Sjögren's syndrome expertise center. Clinical diagnosis by the treating physician was used as the gold standard. Separate analyses were performed for patients who underwent labial or parotid gland biopsies. The average score for hypoechogenic areas in 1 parotid and 1 submandibular gland was determined (range 0-3). Next, performance of the ACR/EULAR criteria was evaluated after addition of SGUS or replacement of current items by SGUS. RESULTS: Receiver operating characteristic analysis showed an optimal cutoff value of ≥1.5 for SGUS. The optimal weight for SGUS positivity was 1. Cutoff for ACR/EULAR fulfilment remained ≥4. In patients who underwent a labial gland biopsy (n = 124), the original criteria showed an area under the curve (AUC) of 0.965, sensitivity of 95.9%, and specificity of 92.2%. After the addition of SGUS, the AUC was 0.966, with a sensitivity of 97.3% and specificity of 90.2%. In patients who underwent a parotid gland biopsy (n = 198), similar results were found. Sensitivity of the criteria decreased substantially when SGUS replaced salivary gland biopsy or anti-SSA antibodies, while performance remained equal when SGUS replaced the ocular staining score, Schirmer's test, or unstimulated whole saliva flow. CONCLUSION: Validity of the ACR/EULAR criteria remains high after incorporation of SGUS. With SGUS, clinicians are offered a larger array of tests to evaluate fulfillment of the ACR/EULAR criteria.
33331312 [Depression and anxiety in patients with psoriatic arthritis: Prevalence and associated fa 2020 Dec 18 OBJECTIVE: To determine the prevalence of depression and anxiety in patients with psoriatic arthritis (PsA), to investigate whether there is a difference in the prevalence of depression and anxiety between PsA and rheumatoid arthritis (RA) patients and to identify associated risk factors for depression and anxiety in PsA patients. METHODS: PsA and RA patients who visited Department of Rheumatology and Clinical Immunology in Peking University First Hospital from May 2018 to Sep 2019 were recruited. Self-rating anxiety scale and self-rating depression scale were surveyed and compared between PsA and RA patients. Demographics and clinical features including age, gender, disease duration, disease activity score, psoriasis area and severity index (PASI), and medical application were collected. Power Doppler and grey-scale ultrasound of joints, tenosynovitis and enthesis were performed. Multivariate Logistic regression was used to identify the factors associated with mood disorders and the odds ratio of depression and anxiety between the PsA and RA patients. RESULTS: Among the 114 enrolled PsA patients, 37 (32.5%) had mood disorders, in which 36 (31.6%) with depression and 15 (13.2%) with anxiety. Compared with 201 RA patients, PsA patients showed greater odds for depression [adjusted OR (95%CI): 2.7 (1.1-6.4)]. Depression was more often observed in the PsA than in the RA patients (31.6% vs. 18.9%, P=0.011). The similar trend for anxiety was also observed, although the difference was insignificant (13.2% vs. 8.5%, P=0.185). Age (OR=0.95, P=0.008), psoriasis duration (OR=0.94, P=0.018), pain visual analogue scale (OR=1.47, P=0.011), PASI score (OR=1.07, P=0.007) and presence of ultrasound enthesitis (OR=4.13, P=0.009) were identified as factors associated with depression in the PsA patients. PASI score (OR=1.07, P=0.001) was identified as associated factor for anxiety in the PsA patients. CONCLUSION: The prevalence of depression and anxiety is elevated in PsA patients. Depression is significantly more prevalent in PsA patients than in RA patients. Younger age, shorter psoriasis duration, worse pain and presence of ultrasound enthesitis are associated with depression, while severe psoriasis rash is associated with both depression and anxiety in PsA patients.
32615849 Impact of glucocorticoids on systemic sirtuin 1 expression and activity in rats with adjuv 2021 Jan The class III histone deacetylase sirtuin 1 (SIRT1) plays a pivotal role in numerous biological and physiological functions, including inflammation. An association between SIRT1 and proinflammatory cytokines might exist. In addition to their important role in inflammation associated with rheumatoid arthritis (RA), proinflammatory cytokines mediate the development of systemic effects. Here, we evaluated systemic SIRT1 expression and enzymatic activity, in peripheral blood mononuclear cells (PBMCs) and in liver isolated from rats with adjuvant-induced arthritis (AIA), treated or not with low or high doses of glucocorticoids (GCs). We also measured the production of tumour necrosis factor alpha (TNF) and interleukin-1 beta (IL-1 beta) in PBMCs and liver. We found that SIRT1 expression and activity increased in PBMCs of AIA rats compared to healthy controls and decreased under GC treatment. Similarly, we observed an increased SIRT1 activity in the liver of AIA rats compared to healthy controls which decreased under high doses of GCs. We also found an increase in IL-1 beta and TNF levels in the liver of AIA rats compared to healthy controls, which decreased under high doses of GC. We did not observe a significant correlation between SIRT1 activity and proinflammatory cytokine production in PBMC or liver. In contrast, a strong positive correlation was found between the liver levels of TNF and IL-1 beta (rho=0.9503, p=7.5x10(-21)). Our results indicate that increased inflammation in AIA rats compared to healthy control is accompanied by an increased SIRT1 activity in both PBMCs and liver, which could be decreased under GC treatment.
33329572 Granulocytic Myeloid-Derived Suppressor Cell Exosomal Prostaglandin E2 Ameliorates Collage 2020 The results of recent studies have shown that granulocytic-myeloid derived suppressor cells (G-MDSCs) can secrete exosomes that transport various biologically active molecules with regulatory effects on immune cells. However, their roles in autoimmune diseases such as rheumatoid arthritis remain to be further elucidated. In the present study, we investigated the influence of exosomes from G-MDSCs on the humoral immune response in murine collagen-induced arthritis (CIA). G-MDSCs exosomes-treated mice showed lower arthritis index values and decreased inflammatory cell infiltration. Treatment with G-MDSCs exosomes promoted splenic B cells to secrete IL-10 both in vivo and in vitro. In addition, a decrease in the proportion of plasma cells and follicular helper T cells was observed in drainage lymph nodes from G-MDSCs exosomes-treated mice. Moreover, lower serum levels of IgG were detected in G-MDSCs exosomes-treated mice, indicating an alteration of the humoral environment. Mechanistic studies showed that exosomal prostaglandin E2 (PGE2) produced by G-MDSCs upregulated the phosphorylation levels of GSK-3β and CREB, which play a key role in the production of IL-10(+) B cells. Taken together, our findings demonstrated that G-MDSC exosomal PGE2 attenuates CIA in mice by promoting the generation of IL-10(+) Breg cells.
32028063 Synthesis and biological evaluation of myricetin-pentadienone hybrids as potential anti-in 2020 Mar Some important pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α and nitric oxide are thought to play key roles in the destruction of cartilage and bone tissue in joints affected by rheumatoid arthritis. In the present study, a series of new myricetin-pentadienone hybrids were designed and synthesized. Majority of them effectively inhibited the expressions liposaccharide-induced secretion of IL-6, TNF-α and NO in RAW264.7. The most prominent compound 5o could significantly decrease production of above inflammatory factors with IC(50) values of 5.22 µM, 8.22 µM and 9.31 µM, respectively. Preliminary mechanism studies indicated that it could inhibit the expression of thioredoxin reductase, resulting in inhibiting of cell signaling pathway nuclear factor (N-κB) and mitogen-activated protein kinases. Significantly, compound 5o was found to effectively inhibit Freund's complete adjuvant induced rat adjuvant arthritis in vivo.
32843964 Assessment of serum levels of anti-cyclic citrullinated peptide antibodies in patients wit 2020 Nov Presence of the anti-cyclic citrullinated peptide (CCP) antibody is considered a hallmark of rheumatoid arthritis, and may be found in patients with other rheumatic diseases, including psoriatic arthritis (PsA). The aim of the present study was to determine whether the anti-CCP antibody was present in patients with psoriasis with and without arthritis. and to determine whether its presence was associated with clinical, serological and treatment data in patients with PsA. The present study was a cross-sectional study, which included 91 patients with psoriasis (41 with arthritis and 48 without arthritis) as well as an age and sex matched control group consisting of 100 healthy individuals. Presence of the anti-CCP antibody was determined using commercially available ELISA kits. Data on clinical, serological and treatment characteristics was obtained from reviewing each patient's medical history. The quality of life and articular inflammatory activity were assessed using the Short Form Health Survey-12 questionnaire. Skin disease was evaluated using the Psoriasis Area Severity Index and body surface area. In the control group, 1% of individuals were positive for the anti-CCP antibody, whereas 17.5% of the psoriasis patients were positive (P<0.001). In the patients with PsA, 20.9% were positive for the antibody, and in patients with psoriasis without joint disease, 14.5% were positive (P=0.58). Patients with polyarticular forms of PsA were more likely to be anti-CCP positive compared with patients with skin disease without arthritis (P=0.009). In the group of patients with PsA, those who were anti-CCP positive were more likely to suffer from polyarticular forms of arthritis, but no differences were found in the quality of life, joint disease activity, degree of skin involvement and treatment requirements (all P>0.05). In conclusion, 17.5% of patients with psoriasis and 20.9% of patients with PsA were positive for anti-CCP antibodies. Polyarticular arthritis was more common in the anti-CCP positive patients compared with the anti-CCP negative patients.
32505115 Immunomodulatory activity of gamma radiation-attenuated Toxoplasma gondii in adjuvant arth 2020 Aug There is growing evidence that some parasitic infections can impact a variety of autoimmune diseases by disease-inducing or protecting capacities. Anti-inflammatory molecules secreted by Toxoplasma gondii and other parasites are capable of preventing some autoimmune disease like arthritis, lupus nephritis and systemic lupus erythematosus by acting on the immune system. Here we aimed to evaluate the protective efficacy of vaccination with Toxoplasma gondii (T. gondii), either gamma radiation-attenuated or not, on an adjuvant arthritis mouse model. Forty female Swiss albino mice were conducted in experiment divided into normal control; mice were injected with Complete Freund's adjuvant (CFA) into the right hind paws; mice vaccinated with irradiated T. gondii in the 3rd group and un-irradiated T. gondii in the 4th group then were injected two weeks later with CFA. Histopathological changes and IL-17, STAT6 and ROR-γ levels in the joints, as well as serum survivin and Anti-CCP, were evaluated. Also, the splenic production of TGF-β1, TGF-βR, IL-23, IL-1β, IFN-γ, TFN-∞, NF(K)β, MMP1 and MMP3 were assessed. Results exhibited an enhancement of the histopathological changes with diminished the rise of IL-17, STAT 6 and ROR- γ within the joints of both vaccinated groups. Also, serum survivin and Anti-CCP, as well as splenic inflammatory cytokines were reduced. It can be concluded that vaccination with un-irradiated or radiation-attenuated T. gondii exerted a protective effect against adjuvant arthritis with better pathological achievement in the radiation-attenuated vaccinated group. Using gamma radiation-attenuated parasite to exclude the delirious effects of imposing infection of live one may pave the way to new preventative modality against rheumatoid arthritis.
32896246 Real-life persistence of golimumab in patients with chronic inflammatory rheumatic disease 2021 May OBJECTIVES: GO-PRACTICE aimed to evaluate the persistence, clinical response and safety of golimumab in adult patients with chronic inflammatory rheumatic disease. METHODS: Prospective observational study with 24 months of follow-up, involving 134 rheumatologists from public or private health establishments in France. The primary outcome was the persistence of golimumab 24 months after initial prescription. Cumulative persistence probabilities were determined from Kaplan-Meier estimates. Secondary outcomes included an evaluation of disease activity and golimumab safety profile. RESULTS: Of 754 consecutively recruited patients, 170 had rheumatoid arthritis (RA) (54.3 years, 74.1% female, 64.7% biologics-naïve), 106 had psoriatic arthritis (PsA) (48.1 years, 70% female, 66.0% biologics-naïve) and 478 had axial spondyloarthritis (axSpA) (42.8 years, 54.6% female, 60.9% biologics-naïve). Golimumab persistence at 2 years was 56.5%, 45.1% and 52.6%, respectively, in RA, PsA and axSpA groups. Persistence was higher in biologics-naïve (58.3%) than in biologics pre-treated patients (42.7%, p<0.01). For 362 patients continuing golimumab at 2 years, disease activity improved significantly from baseline to 2 years: mean 28-joint disease activity score for RA and PsA was lowered by 2.06 and 1.89 points, and mean ankylosing spondylitis disease activity score was lowered by 3.11 points (p<0.0001) for axSpA. Patient appreciation of disease activity also improved; 8.9% of discontinuations were due to intolerance. CONCLUSIONS: Golimumab persistence was satisfactory at 2 years and accompanied by improvements in clinical effectiveness in 362 patients continuing golimumab at 2 years. Golimumab was well tolerated and its safety profile was consistent with those reported in previous studies.
32401403 Therapeutic effect of omega-3 fatty acids on T cell-mediated autoimmune diseases. 2020 Aug The present study was to demonstrate that the G protein coupled receptors serve as targets for the treatment of autoimmune disease such as rheumatoid arthritis and multiple sclerosis. Rats received pristane at the base of the tail. Affected joints were counted daily. The T cell mediated autoimmune diseases such as pristine-induced arthritis (PIA) and autoimmune encephalomyelitis (EAE) in a rat model were profoundly ameliorated by treatment with the specific G protein couple receptors 120 (GPR120) stimuli omega-3 fatty acids (ω-3 FAs). Our study further revealed that the activation of GPR120 by ω-3 FAs can result in a decrease of phosphorylated transforming growth factor-β activated kinase 1 (TAK1), and further inhibit the downstream IKKβ/I-κB pathway and the terminal NF-κB activation which serves as a mediator of T cell activation. ω-3 Fatty acids exhibited an inhibitory effect on TAK1 by enhancing the association of β-arrestin2 and TAK1 binding protein 1 (TAB1), thus the disassociation of TAB1 from the TAB1/TAK1 complex renders a limited effect on β-arrestin2 signaling as an innate immunity regulation. GPR120 is a functional receptor of ω-3 fatty acids in T cell-mediated autoimmune disease compared with its effect on innate immunity.
32194572 IDO and Kynurenine Metabolites in Peripheral and CNS Disorders. 2020 The importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis. Indoleamine-2,3-dioxygenase (IDO) activity exerts a protective function, limiting the severity of experimental arthritis, whereas deletion or inhibition exacerbates the symptoms. Other chronic disorder with an inflammatory component, such as atherosclerosis, are also suppressed by IDO activity. It is suggested that this overall anti-inflammatory activity is mediated by a change in the relative production or activity of Th17 and regulatory T cell populations. Kynurenines may play an anti-inflammatory role also in CNS disorders such as Huntington's disease, Alzheimer's disease and multiple sclerosis, in which signs of inflammation and neurodegeneration are involved. The possibility is discussed that in Huntington's disease kynurenines interact with other anti-inflammatory molecules such as Human Lymphocyte Antigen-G which may be relevant in other disorders. Kynurenine involvement may account for the protection afforded to animals with cerebral malaria and trypanosomiasis when they are treated with an inhibitor of kynurenine-3-monoxygenase (KMO). There is some evidence that changes in IL-10 may contribute to this protection and the relationship between kynurenines and IL-10 in arthritis and other inflammatory conditions should be explored. In addition, metabolites of kynurenine downstream of KMO, such as anthranilic acid and 3-hydroxy-anthranilic acid can influence inflammation, and the ratio of these compounds is a valuable biomarker of inflammatory status although the underlying molecular mechanisms of the changes require clarification. Hence it is essential that more effort be expended to identify their sites of action as potential targets for drug development. Finally, we discuss increasing awareness of the epigenetic regulation of IDO, for example by DNA methylation, a phenomenon which may explain differences between individuals in their susceptibility to arthritis and other inflammatory disorders.
32148544 The Protective Effect of Different Polar Solvent Extracts of Er Miao San on Rats with Adju 2020 OBJECTIVE: The aim of this study was to evaluate the antiarthritic effects of different polar solvent extracts of Er Miao San (EMS) on model rats with adjuvant arthritis (AA) and screen the effective pats of EMS in the treatment of arthritis. METHODS: Four different polar solvent extracts of EMS such as petroleum ether (PE), methylene chloride (CH(2)Cl(2)), ethyl acetate (EtOAc), and n-butanol (n-butanol (. RESULTS: Administration of EtOAc and CH(2)Cl(2) parts remarkably inhibited the paw swelling, decreased the index of arthritis, decreased the body weight loss, and improved the changes of histopathology. Furthermore, the concentrations of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) were significantly lower, while the anti-inflammatory cytokine (IL-10) was remarkably higher compared with that in the model group. And the result of UHPLC analysis indicated that the effective parts of EMS contain berberine and atractylodin. CONCLUSIONS: EtOAc and CH(2)Cl(2) are the effective parts of EMS that can improve arthritis. In particular, berberine and atractylodin may be responsible for the antiarthritic activity of EMS. This research provided pharmacological and chemical foundation for the application of EMS in treating rheumatoid arthritis (RA).