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ID PMID Title PublicationDate abstract
34910211 Deformity analysis of the lower limb on the coronal plane in patients with rheumatoid arth 2021 Aug 13 OBJECTIVES: To evaluate joint orientation angles of the coronal plane in patients with rheumatoid arthritis (RA) in comparison with osteoarthritis (OA). METHODS: In total, 72 patients with RA (90 knees) and 76 patients with OA (90 knees) who underwent total knee arthroplasty were enrolled. The hip-knee-ankle (HKA) angle, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), and joint line convergence angle (JLCA) were measured on preoperative long-leg radiographs in the standing position. Student's t-test was used to assess differences in radiographic data between patients with RA and OA. RESULTS: In knees with RA and OA, the mean HKA was -3.4 ± 9.4° and -10.6 ± 8.0°, the mean mLDFA was 86.6 ± 3.7° and 88.2 ± 2.7°, the mean mMPTA was 85.9 ± 4.0° and 84.3 ± 3.7°, and the mean JLCA was 2.7 ± 4.2° and 6.8 ± 4.1°. All parameters in the knees with RA were more valgus than those with OA. CONCLUSIONS: Knees with RA had a great variability in joint orientation angles on the coronal plane; the whole lower limb alignment and the femur, tibia, and joint were more valgus in knees with RA than with OA.
34450633 Targeting of fibroblast activation protein in rheumatoid arthritis patients: imaging and e 2021 Aug 27 OBJECTIVE: Activated synovial fibroblasts are key effector cells in rheumatoid arthritis (RA). Selectively depleting these based upon their expression of fibroblast activation protein (FAP) is an attractive therapeutic approach. Here we introduce FAP imaging of inflamed joints using [68Ga]Ga-FAPI-04 in an RA patient, and aim to assess feasibility of anti-FAP targeted photodynamic therapy (FAP-tPDT) ex vivo using 28H1-IRDye700DX on RA synovial explants. METHODS: Remnant synovial tissue from RA patients was processed into 6 mm biopsies and, from several patients, into primary fibroblast cell cultures. Both were treated using FAP-tPDT. Cell viability was measured in fibroblast cultures and biopsies were evaluated for histological markers of cell damage. Selectivity of the effect of FAP-tPDT was assessed using flowcytometry on primary fibroblasts and co-cultured macrophages. Additionally, one RA patient intravenously received [68Ga]Ga-FAPI-04 and was scanned using PET/CT imaging. RESULTS: In the RA patient,FAPI-04 PET imaging showed high accumulation of the tracer in arthritic joints with very low background signal. In vitro, FAP-tPDT induced cell death in primary RA synovial fibroblasts in a light dose dependent manner. An upregulation of cell damage markers was observed in the synovial biopsies after FAP-tPDT. No significant effects of FAP-tPDT were noted on macrophages after FAP-tPDT of neighbouring fibroblasts. CONCLUSION: In this study the feasibility of selective FAP-tPDT in synovium of rheumatoid arthritis patients ex vivo is demonstrated. Furthermore, this study provides the first indication that FAP-targeted PET/CT can be used to image arthritic joints, an important step towards application of FAP-tPDT as a targeted locoregional therapy for RA.
34915576 Immunogenicity of sarilumab and impact on safety and efficacy in Japanese patients with rh 2021 Sep 10 OBJECTIVES: To describe the immunogenicity profile of sarilumab in Japanese patients with rheumatoid arthritis (RA). METHODS: Patients enrolled in the KAKEHASI and HARUKA studies were included in our analysis. In these studies, patients received sarilumab 150 mg or 200 mg every 2 weeks for 52 or 28 weeks in combination with methotrexate (MTX) (KAKEHASI), or for 52 weeks as monotherapy or in combination with non-MTX conventional synthetic disease-modifying anti-rheumatic drugs (HARUKA). Anti-drug antibodies (ADAs) and neutralising antibodies (NAbs) were assessed in the pooled population. RESULTS: Positive ADA assay responses occurred in 10/149 (7.1%) patients treated with sarilumab 150 mg and 13/185 (7.0%) patients treated with sarilumab 200 mg, with persistent responses in 2 (1.4%) and 4 (2.2%) patients, respectively. Peak ADA titre was 30. No patients treated with the 150 mg dose and one patient (0.5%) treated with the 200 mg dose exhibited NAbs. There was no evidence of an association between ADA formation and hypersensitivity reactions or reduced efficacy. CONCLUSIONS: ADAs, which occurred at a low frequency and titre, did not affect the safety or efficacy of sarilumab 150 or 200 mg administered as monotherapy or combination therapy in Japanese patients with RA in the KAKEHASI or HARUKA studies.
34888333 Mapping Knowledge Structure and Themes Trends of Osteoporosis in Rheumatoid Arthritis: A B 2021 Background: Rheumatoid arthritis is a chronic disabling disease characterized by chronic inflammation, articular cartilage destruction, and reduced bone mass. Multiple studies have revealed that the development of osteoporosis in rheumatoid arthritis (RA; ORA) patients could be led to a reduced quality of life and increased healthcare costs. Nevertheless, no attempt has been made to analyze the field of ORA research with the bibliometric method. This study aimed to provide a comprehensive overview of the knowledge structure and theme trends in the field of ORA research from a bibliometric perspective. Methods: Articles and reviews regarding ORA from 1998 to 2021 were identified from the Web of Science database. An online bibliometric platform, CiteSpace, and VOSviewer software were used to generate visualization knowledge maps including co-authorship, co-citation, and co-occurrence analysis. SPSS, R, and Microsoft Excel software were used to conduct curve fitting and correlation analysis, and to analyze quantitative indicators, such as publication and citation counts, h-index, and journal citation reports. Results: A total of 1,081 papers with 28,473 citations were identified. Publications were mainly concentrated in North America, Western Europe, and Eastern Asia. Economic strength is an important factor affecting scientific output. The United States contributed the most publications (213) with the highest h-index value (46) as of September 14, 2021. Diakonhjemmet Hospital and professor Haugeberg G were the most prolific institution and influential authors, respectively. Journal of Rheumatology was the most productive journal concerning ORA research. According to the burst references, "anti-citrullinated protein antibodies" and "preventing joint destruction" have been recognized as the hot research issues in the domain. The keywords co-occurrence analysis identified "teriparatide," "interleukin-6," "Wnt," and "vertebral fractures" as the important future research directions. Conclusion: This was the first bibliometric study comprehensively summarizing the trends and development of ORA research. Our findings could offer practical sources for scholars to understand the key information in this field, and identify the potential research frontiers and hot directions in the near future.
34104441 Association of interleukin-17A rs2275913 polymorphism with rheumatoid arthritis susceptibi 2021 OBJECTIVES: Rheumatoid arthritis is a chronic inflammatory autoimmune disease. This study aimed to determine the association of interleukin-17A-197G/A polymorphism with rheumatoid arthritis in Sudanese patients. METHODS: A case-control study was conducted between March and December 2018. Clinical and demographic data of the study participants were collected and analyzed. Polymerase chain reaction restriction fragment length polymorphism molecular technique was done to investigate interleukin-17A-197G/A polymorphisms. All statistical tests were considered statistically significant when p < 0.05. RESULTS: The study population included 266 participants aged between 1 and 85 years, with an average of 40 years, classified into 85 (31.2%) cases (mean age 48.5 ± 11.3 years), and 181 (68.8%) controls (mean age 35.3 ± 15.9 years). The interleukin-17A homozygote AA genotype was more frequent among the control group compared to the case group; 95 (52.5%) and 7 (8.2%), respectively. The homozygote GG and the heterozygote AG genotypes were proportionally not different among the cases and control groups; 13 (54.2%) and 11 (45.8%), and 65 (46.4%) and 75 (53.6%), respectively. According to the distribution of interleukin-17A genotypes, a statistically significant difference was observed among cases with the interleukin-17A AA and AG genotypes, p values 0.001 and 0.004, respectively. For the association interleukin-17A genotypes and family history a negatively significant association was reported (95% confidence interval, -0.219, p value = 0.001). There was also a negatively significant association of interleukin-17A genotypes and anti-cyclic citrullinated peptide (95% confidence interval, -0.141, p value = 0.002). CONCLUSION: This study is the first study in Sudan established the association between interleukin-17A-197G/A (rs2275913) polymorphisms and susceptibly to rheumatoid arthritis. These findings appeal for further research in Sudan to investigate the exact role of IL-17A in immunopathology and disease severity among Sudanese rheumatoid arthritis.
33898490 Synovial Immunohistological Biomarkers of the Classification of Undifferentiated Arthritis 2021 Background: Undifferentiated arthritis (UA) is defined as an inflammatory arthritis that does not fulfill criteria for a definite diagnosis. Delay in reaching a specific diagnostic and therapy may lead to impaired functional outcomes. Our aim was to identify synovial biomarkers associated with definitive diagnostic classification in patients with UA. Methods: DMARD-naïve UA patients with available initial synovial tissue (ST) and a final diagnosis of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) during follow-up were included and compared with patients with well-defined disease (RA or PsA). Clinical, arthroscopic, and pathological data were compared between groups. Pathology included quantitative immunohistochemical (IHC) analysis of cell types and human interferon-regulated MxA. Principal component analysis (PCA) was performed to extract disease patterns. Results: One hundred and five patients were included: 31 patients with DMARD-naïve UA (19 evolving to RA and 12 to PsA during a median follow up of 7 years), 39 with established RA, and 35 with established PsA. ST from the UA group showed higher macrophage density compared with the established RA and PsA groups. Patients with UA evolving to RA (UA-RA) showed higher MxA expression and CD3(+) T-cell density compared with established RA. UA patients evolving to PsA (UA-PsA) showed increased vascularity and lining synovial fibroblast density compared with established PsA. Synovitis of UA-PsA patients showed more mast cells and lining fibroblasts compared with UA-RA. No between-group differences in local or systemic inflammation markers were found. Conclusions: Our results show differences in the cellular composition of UA synovium compared with RA and PsA, with higher density of the cellular infiltrate in the UA groups. Initial expression of the interferon inducible gene MxA could be a biomarker of progression to RA, while higher mast cell and fibroblastic density may be associated with PsA progression.
33385368 Ocular Involvement in Sjögren Syndrome: Risk Factors for Severe Visual Impairment and Vis 2021 May PURPOSE: To assess the risk factors for severe visual impairment (SVI) and corneal complications in primary and secondary Sjögren syndrome (SS). DESIGN: Retrospective case series. METHODS: Ocular data of all consecutive SS patients presenting to an eye-care network and receiving a diagnosis according to 2012 American College of Rheumatology criteria over the past 8 years were reviewed. MAIN OUTCOME MEASUREMENT: risk factors associated with SVI (best-corrected visual acuity <20/200) and vision-threatening corneal complications (ulceration or perforation) at presentation were evaluated using multivariate analysis and odds ratios (OR). RESULTS: Of the 919 patients, 285 (31%) had primary and 634 (69%) had secondary SS. The most common cause of secondary SS was rheumatoid arthritis (98.1%), followed by systemic lupus erythematosus (0.79%), psoriasis (0.79%), and scleroderma (0.6%). Among the 1,838 eyes, SVI was noted in 10%, and 2.5% had corneal complications at presentation. The presence of corneal scarring (P < .00001; OR: 3.00), corneal ulceration (P < .00001; OR: 12.96), low Schirmer values (P = .0084; OR: 0.93), cataract (P = .0036; OR: 2.4), glaucoma (P = .04; OR: 4.09), and age at diagnosis (P = .005; OR: 1.02) were independent risk factors for developing SVI. The risk factors for corneal complications were presence of scleritis (P < .0001; OR: 8.9) and a diagnosis of secondary SS (P = .009; OR: 2.94). CONCLUSIONS: In patients with SS, severity of dryness, corneal ulceration and scarring, cataract, and glaucoma are factors associated with poor visual acuity. Eyes with scleritis have a greater risk of developing vision-threatening corneal complications and therefore should be monitored closely.
34164259 Radiocapitellar arthroplasty. 2021 Aug This article sets out the evidence demonstrating that the clinical need for a prosthetic arthroplasty designed specifically for the radiocapitellar joint has been underestimated. The prevalence of radiocapitellar degenerative change requiring treatment is discussed and the relationship between 'isolated' radiocapitellar joint arthritis and more generalised elbow arthritis is explained. Current literature now supports our view that radiocapitellar joint arthroplasty is not only an effective long-term solution for patients with localised radiocapitellar arthritis but also for those patients with more severe degenerative changes involving the elbow joint irrespective of their cause. We consider that is important to avoid resection of the radial head and therefore that resurfacing implants rather than joint replacement implants are more likely to provide a good longterm outcome for patients with elbow arthritis.
34549015 Majoon Chobchini attenuates arthritis disease severity and RANKL-mediated osteoclastogenes 2021 Oct Majoon Chobchini, a polyherbal Unani compound, has been used holistically in India to treat rheumatoid arthritis. However, the potential mechanism underlying the antiarthritic efficacy of Majoon Chobchini has not been elucidated so far. This study was aimed to explore the underlying molecular mechanism and scientifically validate the therapeutic basis of Majoon Chobchini in rheumatoid arthritis (RA). The anti-arthritic efficacy of Majoon Chobchini was demonstrated in vivo using complete Freund's adjuvant-induced arthritic rat model and adjuvant-induced arthritic fibroblast-like synoviocytes (AA-FLS). The expression of pro-inflammatory mediators and enzymes was evaluated in the serum and synovial tissues of adjuvant-induced arthritis (AIA) rats. In-vitro, AA-FLS, and bone marrow macrophages (BMMs) were co-cultured to evaluate the formation and activity of osteoclasts using TRAP staining analysis and pit formation assay, respectively. RANKL and OPG levels were detected using western blotting and qRT-PCR analysis. Furthermore, the involvement of JAK-STAT-3 signaling in the therapeutic efficacy of Majoon Chobchini was evaluated both in vivo and in vitro. Majoon Chobchini significantly reversed the physical symptoms in AIA rats with reduced expression of pro-inflammatory cytokines and enzymes. Notably, Majoon Chobchini alleviated cartilage degradation and bone erosion in AIA rats via inhibiting the activation of the JAK-STAT-3 signaling pathway in the AIA rats. Consistent with its effect in vivo, Majoon Chobchini decreased osteoclast inducing potential of AA-FLS and thus attenuated osteoclast formation and bone resorption in vitro. Taken together, our findings suggest that the JAK/STAT-3 signaling inhibition may underlie the mechanism through which Majoon Chobchini provides relief against RA symptoms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02985-4.
34692323 Risk Factors Associated With Non-Respondence to Methotrexate in Rheumatoid Arthritis Patie 2021 Sep INTRODUCTION: Oral methotrexate (MTX) is the first-line therapy for patients with rheumatoid arthritis (RA). However, not all RA patients respond to MTX. In this study, we will determine the risk factors associated with MTX failure. METHODS: This retrospective study was conducted in tertiary care hospital in Pakistan. Data of 612 patients who were diagnosed with RA from June 2019 to January 2021 were retrieved from the medical record room. After inclusion, patients were divided into two groups; respondent and non-respondent. Their characteristics and demographics were compared. RESULTS: Out of the total 612 patients, 112 (18.3%) were labelled as non-respondent to MTX. Non-respondents had a higher predominance of females (86.6% vs. 60.2%; p-value: 0.001), participants with body mass index (BMI) >25 kg/m(2) (54.4% vs. 22.4%; p-value: <0.00001), smokers (34.8% vs. 18.2%; p-value: 0.0001), participants with diabetes (47.3% vs. 23.4%; p-value: <0.0001) and rheumatoid factor positivity (91.0% vs. 64.8%; p-value: <0.0001). CONCLUSION: Female gender, higher BMI, smoking, higher disease activity, and diabetes were associated with MTX failure. These easily available parameters can help predict the disease process and outcome of treatment. It is important to screen patients who are at risk of MTX failure, so a contingent treatment plan can be devised, in case patients do not respond to MTX.
34250763 Sustained Remission in Rheumatoid Arthritis: Time to Withdraw Treatment? 2021 Aug With increasing numbers of patients with rheumatoid arthritis achieving sustained remission, medication withdrawal is an important consideration to reduce polypharmacy and associated adverse events. An article from the journal Arthritis & Rheumatology (1) explores the treatment withdrawal options for patients on etanercept and methotrexate combination therapies and suggests methotrexate withdrawal has the least impact on disease worsening. There are limitations in the study, including the use of only one disease activity score and no assessment of radiographic progression, but, overall, the article provides a good framework for future studies on treatment withdrawal options and the possibility of medication reduction for patients.
34630657 Panax notoginseng saponins alleviate osteoporosis and joint destruction in rabbits with an 2021 Nov Although a number of anti-rheumatic drugs and biologics may be used to alleviate the symptoms of rheumatoid arthritis (RA), these compounds have been associated with bone loss and joint destruction; thus, alternative treatment approaches are required. In the present study, various plant extracts were evaluated for their capacity to inhibit joint destruction, and Panax notoginseng saponins (PNS), obtained from the Traditional Chinese Medicine Panax notoginseng, was identified as such a compound. Therefore, a rabbit antigen-induced arthritis (AIA) model was generated by immunization with ovalbumin in Freund's complete adjuvant, followed by treatment with PNS for 3 months. The morphology of the quadriceps femoris muscle, cartilage chondrocytes and skeletal elements was histologically observed by transmission electron microscopy (TEM), as well as micro-computed tomography. The results revealed that PNS significantly reduced the histopathological alterations associated with arthritic muscular atrophy and inflammation. In addition, TEM demonstrated that PNS protected chondrocytes from RA-associated damage. Furthermore, the bone density and microarchitecture in rabbits treated with PNS were markedly improved compared with those of the model group. Collectively, these data indicated that treatment with PNS may relieve osteoporosis and prevent joint and bone destruction in AIA.
34646130 WTD Attenuating Rheumatoid Arthritis via Suppressing Angiogenesis and Modulating the PI3K/ 2021 Background: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported. Purpose: The aim of this study was to explore the possible mechanism of WTD against RA and a promising alternative candidate for RA therapy. Methods: A model of collagen-induced arthritis (CIA) was constructed in rats to assess the therapeutic effects of WTD. Histopathological staining, immunofluorescence, and western blotting of synovial sections were conducted to detect the antiangiogenic effects of WTD. Then, cell viability assays, flow cytometry, scratch healing assays, and invasion assays were conducted to explore the effects of WTD on MH7A human fibroblast-like synoviocyte (FLS) cell proliferation, apoptosis, migration, and invasion in vitro. The ability of WTD to induce blood vessel formation after MH7A cell and human umbilical vein endothelial cell line (HUVEC) coculture with WTD intervention was detected by a tube formation assay. The mechanisms of WTD were screened by network pharmacology and confirmed by in vivo and in vitro experiments. Results: WTD ameliorated the symptoms and synovial pannus hyperplasia of CIA rats. Treatment with WTD inhibited MH7A cell proliferation, migration, and invasion and promoted MH7A apoptosis. WTD could inhibit MH7A cell expression of proangiogenic factors, including VEGF and ANGI, to induce HUVEC tube formation. Furthermore, the PI3K-AKT-mTOR-HIF-1α pathway was enriched as a potential target of WTD for the treatment of RA through network pharmacology enrichment analysis. Finally, it was confirmed in vitro and in vivo that WTD inhibits angiogenesis in RA by interrupting the PI3K-AKT-mTOR-HIF-1α pathway. Conclusion: WTD can inhibit synovial hyperplasia and angiogenesis, presumably by inhibiting the migration and invasion of MH7A cells and blocking the production of proangiogenic effectors in MH7A cells. The possible underlying mechanism by which WTD ameliorates angiogenesis in RA is the PI3K-AKT-mTOR-HIF-1α pathway.
33982199 Infliximab prevents systemic bone loss and suppresses tendon inflammation in a collagen-in 2021 Jun Reduced Bone Mineral Density (BMD) and tendon abnormalities, such as tenosynovitis and enthesitis, are prevalent comorbidities in patients with rheumatoid arthritis (RA). The aim of the present study was to investigate the effect of chronic treatment with infliximab on BMD and tendon inflammation in an animal model of inflammatory arthritis. Collagen-Induced Arthritis (CIA) was induced in rats, followed by long-term intraperitoneal administration of infliximab. Two additional groups of animals received methotrexate either as a monotherapy or as a co-treatment to infliximab. BMD was evaluated by Micro-Computed Tomography (Micro-CT) and bone histological examination. Tendon inflammation was assessed histologically and by quantitative ELISA analysis of pro-inflammatory cytokines in tendon tissues. Both methotrexate and infliximab treatment alleviated joint inflammation and reduced paw edema. Infliximab-treated animals exhibited an improved trabecular microarchitecture on micro-CT and histological analysis compared to both non-treated and methotrexate-treated animals. Infliximab almost reversed the pathological changes in tendons induced by CIA. Finally, we observed statistically significant declines in tendon TNF-a and IL-23 levels after infliximab treatment. Our study provides evidence that infliximab prevents arthritis-related osteoporosis and suppresses tendon inflammation in an animal model of inflammatory arthritis, in addition to controlling disease activity. These findings offer perspectives for the management of osteoporosis and enthesitis in RA.
33679704 Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rhe 2020 Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)(2)D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.
34600581 Shikonin attenuates rheumatoid arthritis by targeting SOCS1/JAK/STAT signaling pathway of 2021 Oct 2 BACKGROUND: Rheumatoid arthritis is a progressive and systemic autoimmune disease seriously compromises human health. Fibroblast like synoviocytes are the major effectors of proliferation and inflammation in rheumatoid arthritis synovial tissue. Shikonin has anti-inflammatory and immunomodulatory activities. But, its role on synovitis of rheumatoid arthritis is unknown. METHODS: The DBA/1 male mice were randomly divided into the following three groups (n = 6): (1) the normal control group of mice, (2) the CIA (collagen-induced arthritis) group in which mice suffered from arthritis induced by collagen, (3) the SKN (shikonin) group of mice which got arthritis and given intragastrically with shikonin 4 mg/kg per day continuously for 20 days,(4) the MTX (methotrexate) group of mice which got arthritis and orally administration with shikonin 0.5  mg/kg once two days continuously for 20 days. The therapeutic effect of shikonin on collagen induced arthritis mice was tested by arthritis incidence rate, arthritis score and inflammatory joint histopathology. The invasion, adhesion and migration of fibroblast like synoviocytes induced by tumor necrosis factor-α were applied to measure the anti-synovitis role of shikonin. The effect of shikonin on expression of interleukin-6, interleukin-1β and tumor necrosis factor-α was measured by enzyme linked immunosorbent assay. The interaction between shikonin and suppressor of cytokine signaling 1 was verified by molecular docking. The signaling pathways activated by shikonin were measured by western blot. RESULTS: Shikonin decreased the arthritis score and arthritis incidence, and inhibited inflammation of inflamed joints in collagen induced arthritis mice. And shikonin reduced the number of vimentin(+)cells in collagen induced arthritis mice inflamed joints. Meanwhile, shikonin suppressed tumor necrosis factor-α-induced invasion, adhesion and migration of fibroblast like synoviocytes and reduced the expression of interleukin-6, interleukin-1β and tumor necrosis factor-α. And we found that shikonin targeted suppressor of cytokine signaling 1. More interestingly, shikonin blocked the phosphorylation of Janus kinase 1/signal transducer andactivator of transcription 1/signal transducer andactivator of transcription 6 in synovial tissues and in fibroblast like synoviocytes. CONCLUSION: Shikonin represents a promising new anti-rheumatoid arthritis drug candidate that has anti-synovitis effect in collagen induced arthritis mice and inhibits tumor necrosis factor-α-induced fibroblast like synoviocytes by targeting suppressor of cytokine signaling 1/ Janus kinase/signal transducer andactivator of transcription signaling pathway. These findings demonstrate that shikonin has anti-synovitis effect and has great potential to be a new drug for the treatment of rheumatoid arthritis.
33238804 A case of enteropathic arthritis complicated by superimposed bilateral septic arthritis of 2021 Jul Polyarticular septic arthritis is an underappreciated clinical entity. Pre-existing joint diseases, such as osteoarthritis and rheumatoid arthritis have been shown to be risk factors for septic arthritis. However, there is a paucity of data in the literature regarding the risk of septic arthritis in those patients with enteropathic arthritis. Here, we describe the case of a 47-year-old female with a background history of ulcerative colitis who presented with difficulty mobilising and pain in the hips associated with lethargy, fever and a significant inflammatory response. After an investigative process, she was newly diagnosed with enteropathic arthritis, complicated at presentation, by bilateral septic arthritis of the hips, based on progressive radiological destruction and a joint aspirate that grew Staphylococcus aureus. After treatment with antibiotics and steroids, her pain and mobility significantly improved, and she was discharged with a plan for an elective hip replacement and to commence disease-modifying therapy with sulfasalazine. This case reminds us that we must have a high index of suspicion to diagnose septic arthritis in those who present feverish and unwell with joint pain, even in those who present with multiple joint involvement. Furthermore, it describes a rare occurrence of bilateral septic arthritis of the hips occurring in a patient with enteropathic arthritis, which unlike osteoarthritis and rheumatoid arthritis, is not well described in the literature as a risk factor for septic arthritis.
34868778 Ventricular Arrhythmia Associated With Magnesium and Vitamin D Deficiencies in a Patient W 2021 Oct Prolongation of QT associated with electrolyte changes can lead to ventricular arrhythmias. Correction and supply of calcium, magnesium, and potassium are essential to managing this condition. In this report, we present a case of QT prolongation due to magnesium and vitamin D deficiency in a patient with rheumatoid arthritis.
34262385 Interstitial Lung Disease and its Associations in Rheumatoid Arthritis: Data from a Distri 2021 CONTEXT: Interstitial lung disease (ILD) is a frequent pulmonary manifestation of rheumatoid arthritis (RA). No Sri Lankan studies have determined the prevalence of lung disease in RA and its associations. AIMS: To find the prevalence of ILD in RA and its association with rheumatoid factor (RF), erosions, Disease activity score in 28 joints (DAS 28), disease duration, Body mass index(BMI), erythrocyte sedimentation rate (ESR), smoking, and also to determine the prevalence of lung disease with demographic factors like age, sex, and income. SETTINGS AND DESIGN: Questionnaire based retrospective study at a District General Hospital in Sri Lanka. MATERIALS AND METHODS: Diagnosed RA patients included through convenient sampling as it was a simple method that could facilitate data collection in a short duration. Since all patients with a diagnosis of RA were eligible, all consecutive patients with a diagnosis of RA at the rheumatology clinics were included in the study. To reduce the bias a large sample of patients were used as well as patients attending different rheumatology clinics were included and also patients who were referred to the hospital from peripheries were included in the study. The calculated sample size was 384 and according to patient numbers attending clinics, a period of 6 months was decided to select the study sample. STATISTICAL ANALYSIS USED: Chi-Square calculation and logistic regression analysis using Minitab 17 software. RESULTS: From 384 patients, the prevalence of ILD was 14.58%, been 5.4% in early RA (<2 years disease duration). Mean age of ILD group was 52.94 years (95% CI 64.66-41.22). Mean RA duration was 7.69 years (95% CI, 2.38-12.99). Male to female sex ratio of RA was 1:7, and that of ILD was 2:9. DAS 28 was 4.58 (95% CI, 3.48-5.68). Statistically significant associations were noted with ILD and DAS 28 (P = .0006), ESR (P = .005), RF (P = .03), erosions (P < .00001), and smoking (P < .05). Mean BMI was 22.67 kg and 75.78% had low income (<50 000 rupees/month = 327 US $). CONCLUSIONS: ILD significantly associates RA severity indices like DAS 28, ESR, erosions, RF, and also with smoking. No significant association was found with BMI or gender difference. Therefore, disease severity indices could be used to predict progression to ILD in RA.
33986757 TCRβ Sequencing Reveals Spatial and Temporal Evolution of Clonal CD4 T Cell Responses in 2021 Effective tolerogenic intervention in Rheumatoid Arthritis (RA) will rely upon understanding the evolution of articular antigen specific CD4 T cell responses. TCR clonality of endogenous CD4 T cell infiltrates in early inflammatory arthritis was assessed to monitor evolution of the TCR repertoire in the inflamed joint and associated lymph node (LN). Mouse models of antigen-induced breach of self-tolerance and chronic polyarthritis were used to recapitulate early and late phases of RA. The infiltrating endogenous, antigen experienced CD4 T cells in inflamed joints and LNs were analysed using flow cytometry and TCRβ sequencing. TCR repertoires from inflamed late phase LNs displayed increased clonality and diversity compared to early phase LNs, while inflamed joints remained similar with time. Repertoires from late phase LNs accumulated clones with a diverse range of TRBV genes, while inflamed joints at both phases contained clones expressing similar TRBV genes. Repertoires from LNs and joints at the late phase displayed reduced CDR3β sequence overlap compared to the early disease phase, however the most abundant clones in LNs accumulate in the joint at the later phase. The results indicate CD4 T cell repertoire clonality and diversity broadens with progression of inflammatory arthritis and is first reflected in LNs before mirroring in the joint. These observations imply that antigen specific tolerogenic therapies could be more effective if targeted at earlier phases of disease when CD4 T cell clonality is least diverse.