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ID PMID Title PublicationDate abstract
34781187 Matrine inhibits synovial angiogenesis in collagen-induced arthritis rats by regulating HI 2022 Jan Matrine (Mat) is an alkaloid of tetracycline quinazine, and previous studies have demonstrated its specific effect on relieving rheumatoid arthritis (RA). However, the effect of Mat on joint synovial angiogenesis in the pathogenesis of RA has not been elucidated. In this study, body weight, joint swelling, arthritis index (AI) score, histopathological changes, immunohistochemical, and western blot- were used in collagen-induced arthritis (CIA) rats to detect pro-inflammatory factors and, - expression levels of key cytokines and proteins along the hypoxia-inducible factor (HIF)-endothelial growth factor (VEGF)-angiopoietin (Ang) axis and VEGF-phosphoinositide 3-kinase (PI3K) / protein kinase B (Akt) pathway. In vitro experiments were conducted to observe the effect of Mat on the proliferation, migration and lumen formation of RA-fibroblast-like synovial cells (FLS) and human umbilical vein endothelial cells (HUVECs). Results showed that Mat reduced the degree of paw swelling and AI score in CIA rats, joint synovial tissue proliferation, inflammatory cell infiltration, and neovascularization; moreover, it down-regulated the expression levels of inflammatory factors interleukin-1β, interferon-γ, and pro-angiogenic factors VEGF, placental growth factor, HIF-α, Ang-1, Ang-2, Tie-2, and phosphorylation-Akt in the ankle joint of CIA rats. In addition, the in vitro experiments showed that Mat inhibited the proliferation and migration of RA-FLS and inhibited the proliferation and lumen formation of HUVECs. Therefore, Mat exerts an anti-angiogenesis effect by regulating the HIF-VEGF-Ang axis and inhibiting the PI3K/Akt signaling pathway. This inhibits the pathogenesis and improve the symptoms of RA, and may be offered as a candidate drug for the treatment of RA.
35574971 Understanding prescribed dose in hand strengthening exercise for rheumatoid arthritis: A s 2022 May 16 OBJECTIVE: 1) To identify therapist or participant characteristics associated with prescribed dose of hand strengthening exercise in adults with rheumatoid arthritis and 2) To determine the impact of dose prescribed on outcome (hand function and grip strength). METHODS: Overall dose was calculated using area under the curve (AUC). Analysis 1 assessed the association between therapist professional background, therapist grade, baseline participant physical and psychological characteristics and prescribed dose. Analyses 2 and 3 estimated the relationship between prescribed dose and overall hand function and grip strength. Generalised estimating equation linear regression analysis was used. RESULTS: Analysis 1: Being treated by an occupational therapist (β = -297.0, 95% CI -398.6, -195.4), metacarpophalangeal joint deformity (β = -24.1, 95% CI -42.3, -5.9), a higher number of swollen wrist/hand joints (β = -11.4, 95% CI -21.6, -1.2) and the participant feeling downhearted and low all of the time (β = -293.6, 95% CI -436.1, -151.1) were associated with being prescribed a lower dose. Being treated by a grade 6 therapist (β = 159.1, 95% CI 65.7, 252.5), higher baseline grip strength (β = 0.15, 95% CI 0.02, 0.28) and greater participant confidence to exercise without fear of making symptoms worse (β = 18.9, 95% CI 1.5, 36.3) were associated with being prescribed a higher dose. Analyses 2 and 3: Higher dose was associated with greater overall hand function (β = 0.005, 95% CI 0.001, 0.010) and full-hand grip strength (β = 0.014, 95% CI 0.000, 0.025) at 4-month. CONCLUSION: Higher dose was associated with better clinical outcomes. Prescription of hand strengthening exercise is associated with both therapist and participant characteristics.
35327515 Periodontal Disease Augments Cardiovascular Disease Risk Biomarkers in Rheumatoid Arthriti 2022 Mar 19 OBJECTIVES: Periodontal disease (PD) and rheumatoid arthritis (RA) are known chronic conditions with sustained inflammation leading to osteolysis. Cardiovascular diseases (CVD) are frequent comorbidities that may arise from sustained inflammation associated with both PD and RA. In order to determine CVD risk, alterations at the molecular level need to be identified. The objective of this study, therefore, was to assess the relationship of CVD associated biomarkers in RA patients and how it is influenced by PD. METHODS: The study consisted of patient (26 RA with PD, 21 RA without PD, 51 patients with PD only) and systemically and periodontally healthy control (n = 20) groups. Periodontal parameters bleeding on probing, probing pocket depth, and marginal bone loss were determined to characterize the patient groups. Proteomic analysis of 92 CVD-related protein biomarkers was performed using a multiplex proximity extension assay. Biomarkers were clustered using the search tool for retrieval of interacting genes (STRING) to determine protein-protein interaction (PPI) networks. RESULTS: RA patients with PD had higher detection levels for 47% of the measured markers (ANGPT1, BOC, CCL17, CCL3, CD4, CD84, CTRC, FGF-21, FGF-23, GLO1, HAOX1, HB-EGF, hOSCAR, HSP 27, IL16, IL-17D, IL18, IL-27, IL6, LEP, LPL, MERTK, MMP12, MMP7, NEMO, PAPPA, PAR-1, PARP-1, PD-L2, PGF, PIgR, PRELP, RAGE, SCF, SLAMF7, SRC, THBS2, THPO, TNFRSF13B, TRAIL-R2, VEGFD, VSIG2, and XCL1) as compared to RA without PD. Furthermore, a strong biological network was identified amongst these proteins (clustering coefficient = 0.52, PPI enrichment p-value < 0.0001). Coefficients for protein clusters involved in CVD (0.59), metabolic (0.53), and skeletal (0.51) diseases were strongest in the PD group. CONCLUSION: Periodontal disease augments CVD-related biomarkers in RA through shared pathological clusters, concurrently enhancing metabolic and skeletal disease protein interactions, independent of autoimmune status.
35546376 Th17.1 lymphocytes: emerging players in the orchestra of immune-mediated inflammatory dise 2022 May 11 It is now well established that Th17 lymphocytes associate with myriad immune-mediated inflammatory diseases. Over the past one and a half decades, a subset of Th17 lymphocytes viz. Th17.1 lymphocytes has been identified in pre-clinical and clinical models of inflammatory rheumatic diseases. These lymphocytes secrete IL-17A (signature cytokine of Th17 lymphocytes) as well as IFN-γ (the signature cytokine of Th1 lymphocytes). They express the chemokine markers for Th1 (CXCR3) as well as Th17 (CCR6) lymphocytes. Th17.1 lymphocytes also express the drug efflux protein p-glycoprotein, which associates with resistance to corticosteroids and other immunosuppressive drugs. This narrative review overviews the evidence regarding Th17.1 lymphocytes in different inflammatory rheumatic diseases. It is now recognized that Th17.1 lymphocytes are increased in the synovial fluid of affected joints in rheumatoid arthritis (RA) and associate with poor treatment response to abatacept. Th17.1 lymphocytes from synovial fluid of RA are less responsive to immunosuppression than those from the peripheral blood. In sarcoidosis, Th17.1 lymphocytes are concentrated in mediastinal lymph nodes and alveolar lining. Such Th17.1 lymphocytes in sarcoidosis are the predominant source of IFN-γ in the sarcoid lung. Th17.1 lymphocytes are elevated in lupus and Takayasu arteritis and associate with disease activity. Future studies should evaluate isolated Th17.1 lymphocytes from peripheral blood or sites of pathology such as synovial fluid and assess their modulation with immunosuppressive therapy in vitro. The analysis of gene expression signature of isolated Th17.1 lymphocytes might enable the identification of newer therapeutic strategies specifically targeting these cell populations in inflammatory rheumatic diseases. Key Points • Th17.1 lymphocytes are a subset of Th17 lymphocytes secreting both IFN-γ and IL-17 • Th17.1 lymphocytes drive neutrophilic inflammation, granuloma formation, and corticosteroid resistance • Th17.1 lymphocytes are elevated in rheumatoid arthritis and sarcoidosis at sites of inflammation • Increased circulating Th17.1 lymphocytes have been identified in lupus and Takayasu arteritis and associate with active disease.
32491812 Adalimumab. 2022 Jan Adalimumab is a fully human, high-affinity, recombinant anti-tumor necrosis factor (TNF) alpha monoclonal antibody used to treat rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, Crohn disease, ulcerative colitis, etc. This activity covers the indications, mechanism of action, dosing, contraindications, and adverse events of this drug, as needed by the interprofessional healthcare team members to utilize it effectively for patient treatment.
34896652 An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases cl 2022 Mar Anti-Ro52 (or anti-TRIM21) antibodies are part of the family of anti-Ro/SSA antibodies, historically markers of Sjögren syndrome and systemic lupus erythematosus. Anti-Ro52 antibodies represent one the most frequently encountered autoantibodies in patients with connective tissue disease (primary Sjögren syndrome, systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myopathies). Because of their lack of specificity and detection in patients with non-autoimmune disorders, the usefulness of anti-Ro52 testing in connective tissue diseases is still matter of debate among clinicians and immunologists. Autoantibodies are mainly diagnostic markers for autoimmune diseases but some of them can also be directly involved in the generation of tissue damage. Over the past decade several authors reported associations of anti-Ro52 antibodies with some clinical features - especially interstitial lung disease - and survival in patients with connective tissue diseases. There is also a growing evidence of the role of anti-Ro52 antibodies in the pathogenesis of connective tissue diseases. In this review, we comprehensively discuss the clinical associations of anti-Ro52 antibodies in the different connective tissue diseases and the recent advances on their potential role in the inflammatory response.
35633390 Effectiveness of aquatic exercise in the treatment of inflammatory arthritis: systematic r 2022 May 28 Spondyloarthritis and rheumatoid arthritis are classified as inflammatory arthritis and represent a significant source of pain and disability. Non-pharmacological intervention with physical exercise is among the therapeutic approaches most used by health professionals. This study aimed to investigate the effectiveness of aquatic exercise in the treatment of inflammatory arthritis. The review was registered on the PROSPERO (CRD42020189602). The databases (PubMed, PEDro, Web of Science, and SciELO) were searched for studies involving adults with inflammatory arthritis and subjected to rehabilitation with aquatic exercise compared to any other control group, from the year 2010 to March 2022. Pain, disease activity, and physical function were regarded as primary outcomes. Two reviewers completed the eligibility screening and data extraction, and disagreements were resolved by a third reviewer. The methodological quality was assessed using the PEDro scale. A total of 5254 studies were identified, and nine articles were included, totalling 604 participants. Regarding pain, two studies showed that aquatic exercise was superior to home exercise. One study showed that disease activity was significantly improved in the aquatic group compared to the land-based exercise and the control groups (no exercise). Two studies reported that therapy containing aquatic exercise was able to improve physical function. Overall, the studies included in this review indicate that aquatic exercise is effective in treating pain, disease activity, and physical function in individuals with inflammatory arthritis. However, further studies carrying stronger evidence should be conducted to determine whether the treatment with aquatic exercise is superior to other types of therapies.
35321461 Musculoskeletal disorders among the population in Northwest Ethiopia. 2022 OBJECTIVE: This study aimed to assess the magnitude and patterns of chronic musculoskeletal disorders among the population in East Gojjam zone, Northwest Ethiopia. METHODS: A community-based cross-sectional study with 846 recruited study participants was done using a multistage sampling technique in conjunction with a simple and systematic random sampling technique. Face-to-face interviews, physical examinations, a semi-structured questionnaire adapted from the Community Oriented Program for Control of Rheumatic Diseases, and other literature were used to collect data. EpiData 3.1 was used to enter the data, which were then exported to STATA 14.0 for analysis. RESULT: The study had a response rate of 98.8%, with about 836 people out of a total of 846 expected to take part. The magnitude of musculoskeletal disorders was found to be 40.1%. Back pain was the most common musculoskeletal condition (16%) of the population, followed by osteoarthritis (10%) and other forms of arthritis (rheumatoid arthritis (8%), gout arthritis (6%)). The most common comorbidity (multimorbidity) patterns were hypertension (9.8%), diabetes (5.6%), obesity (3.9%), and others (2.2%). CONCLUSION: Almost one in four participants have at least one musculoskeletal disorder in Northwest Ethiopia. Rheumatoid arthritis, osteoarthritis, low back pain, and gout arthritis were the most common musculoskeletal disorders. The most common comorbidity patterns were hypertension, diabetes, obesity, and others. An in-depth investigation of the musculoskeletal burden at the national level will be critical for implementing evidence-based strategies, as well as early detection and screening, linking to health institutions, and direct interventions.
35014966 Optimizing Readability and Format of Plain Language Summaries for Medical Research Article 2022 Jan 11 BACKGROUND: Plain language summaries (PLSs) are intended to provide readers with a clear, nontechnical, and easily understandable overview of medical and scientific literature; however, audience preferences for specific PLS formats have yet to be fully explored. OBJECTIVE: This study aims to evaluate the preferred readability level and format for PLSs of medical research articles of different disease states via a web-based survey of audiences of different age groups. METHODS: Articles describing phase III clinical trials published in top-level, peer-reviewed journals between May 2016 and May 2018 were identified for 3 chronic disease states representing a range of adult patient age groups: (1) psoriasis, a skin disease representative of younger patients; (2) multiple sclerosis (MS), a neurological disease representative of middle-aged patients; and (3) rheumatoid arthritis (RA), a painful joint disease representative of older patients. Four PLSs were developed for each research article, of which 3 were text-only summaries (written with high, medium, and low complexity) and 1 was an infographic. To evaluate each of the 4 PLS formats, a 20-question open survey (specific to one of the 3 diseases) was sent to a representative sample selected via UK-based patient association websites, Twitter, and Facebook patient groups. A weighted-average calculation was applied to respondents' ranked preferences for each PLS format. RESULTS: For all 3 articles, the weighted-average preference scores showed that infographic (psoriasis 2.91, MS 2.71, and RA 2.78) and medium-complexity text-based PLS (reading age 14-17 years, US Grade 9-11; psoriasis 2.90; MS 2.47; RA 2.77) were the two most preferred PLS formats. CONCLUSIONS: Audience preferences should be accounted for when preparing PLSs to accompany peer-reviewed original research articles. Oversimplified text can be viewed negatively, and graphical summaries or medium-complexity text-based summaries appear to be the most popular. PLAIN LANGUAGE SUMMARY: Patients and caregivers should have the chance to read about medical research in a format they can understand. However, we do not know much about the formats that people with different illnesses or ages prefer. Researchers wanted to find out more about this. They selected 3 medical articles about illnesses that affect different age groups: psoriasis (younger patients), multiple sclerosis (middle-aged patients), and rheumatoid arthritis (older patients). They created 4 summaries of each article. One was a graphical summary, and the other 3 were words-only summaries of high, medium, and low complexity. Then, the researchers posted surveys on UK patient group websites and Facebook patient groups to ask people what they thought of the summaries. The surveys were taken by 167 people. These people were patients with psoriasis, multiple sclerosis, or rheumatoid arthritis, or their caregivers. Most were women, and about half had a university degree. For each illness, most people preferred the graphical summary. Among the word-only summaries, most people preferred the medium-complexity wording written for a reading age of 14 to 17 years. People felt that the graphical and medium-complexity summaries were clear and concise, while the others used jargon or were too simple. Authors of medical articles should remember these results when writing summaries for patients. More research is needed about the preferences of other people, such as those with other illnesses. (See Multimedia Appendix 1 for the graphical summary of the plain language summary.).
35310712 Methotrexate-associated proliferative disorder in the lower esophagus extending to the gas 2022 Apr A 64-year-old woman was receiving oral methotrexate (MTX) for rheumatoid arthritis (RA) for 15 years. She underwent esophagogastroduodenoscopy because of discomfort in the chest. Endoscopic findings revealed an ulcer in the lower esophagus extending to the gastroesophageal junction (EGJ). The ulcer occupied half of the esophageal lumen and had a sharp and clear margin. Magnifying narrow-band imaging endoscopy revealed the deposition of white plaque, and there were few microvessels in the edge and bottom of the ulcer. Histologic examination of the biopsy specimens from the oral edge of the lesion revealed proliferation of atypical lymphoid cells (immunophenotype results: CD20 [+], CD3 [partially +], CD5 [-], and BCL-2 [-]]. The patient was diagnosed with methotrexate-associated lymphoproliferative disorder (MTX-LPD) and was advised to stop MTX intake. After 2 months of stopping MTX, the ulcer was found to be almost regressed and showed signs of healing. MTX-LPD in the lower esophagus extending to the EGJ is extremely rare. This case can help in expanding the understanding of esophageal MTX-LPD.
35302407 Rheumatoid Arthritis in Spine Surgery: A Systematic Review and Meta-Analysis. 2022 Mar 18 STUDY DESIGN: Systematic Review and Meta-analysis. OBJECTIVE: The purpose of this study is to synthesize recommendations for perioperative medical management of RA patients and quantify outcomes after spine surgery when compared to patients without RA. METHODS: A search of available literature on patients with RA and spine surgery was performed. Studies were included if they provided a direct comparison of outcomes between patients undergoing spine surgery with or without RA diagnosis. Meta-analysis was performed on operative time, estimated blood loss, hospital length of stay, overall complications, implant-related complications, reoperation, infection, pseudarthrosis, and adjacent segment disease. RESULTS: Included in the analysis were 9 studies with 703 patients with RA undergoing spine surgery and 2569 patients without RA. In RA patients compared to non-RA patients undergoing spine surgery, the relative risk of infection was 2.29 times higher (P = .036), overall complications 1.61 times higher (P < .0001), implant-related complications 3.93 times higher (P = .009), and risk of reoperation 2.45 times higher (P < .0001). Hospital length of stay was 4.6 days longer in RA patients (P < .0001). CONCLUSIONS: Treatment of spinal pathology in patients with RA carries an increased risk of infection and implant-related complications. Spine-specific guidelines for perioperative management of antirheumatic medication deserve further exploration. All RA patients should be perioperatively co-managed by a rheumatologist. This review helps identify risk profiles in RA specific to spine surgery and may guide future studies seeking to medically optimize RA patients perioperatively.
35219890 Trained immunity and inflammation in rheumatic diseases. 2022 Feb 24 BACKGROUND: Rheumatic diseases include a variety of autoimmune and autoinflammatory conditions that are characterised by musculoskeletal involvement and systemic disease. Both innate and adaptive immunity can contribute to the complex inflammatory processes that take part in the pathogenesis of these debilitating disorders. FINDINGS: Over the past decade, studies have led to a paradigm-shift around the concept of immune memory, generating the knowledge that cells of the innate immune system can develop a de facto memory mediated by epigenetic reprograming and metabolic changes (trained immunity). Here we provide an overview of current data that describe features of trained immunity in rheumatic diseases. We link evidence on inflammatory mediators and cytokine production, immunometabolism and epigenetic regulation of immunological programs, and outline the fact that trained immunity could play mechanistic roles in rheumatic diseases such as gout, rheumatoid arthritis, systemic lupus erythematosus or systemic sclerosis. CONCLUSION: This review describes recent findings in several important rheumatic disorders and emphasizes changes in the functional program of innate immune cells that are reminiscent of a trained immune phenotype. Further assessment of trained immunity in rheumatic disease can provide targetable mechanisms that could potentially alter the disease symptomatology and evolution.
35537698 The emerging role of ultrasound in detecting interstitial lung disease in patients with rh 2022 May 7 OBJECTIVE: To investigate the potential role of US in the detection of ILD in a cohort of patients with RA. METHODS: Patients with diagnosis of RA were consecutively enrolled. All patients underwent pulmonary examination, laboratory data, DLCO measure, chest HRCT and radiographs, and US examination. A healthy group was included as control group.US was performed according the 14-intercostal space scanning protocol using the following semiquantitative scale [0 = normal (≤5 B-lines); 1 = slight (≥6 and ≤15 B-lines); 2 = moderate, (≤16 and ≥30 B-lines); 3 = severe (≥30 B-lines)]. RESULTS: A total of 74 RA patients and 74 healthy controls were included. Thirty of 74 patients (40.5%) showed US signs of ILD with respect to the healthy controls (3 subjects, 4.1%) (p < 0.001); whereas HRCT showed ILD in 27 (36.4%) of 74 patients. Among the 30 patients that showed US findings of ILD, 17 (56.6%) were asymptomatic from respiratory view-point. The sensitivity and specificity of US were 92% and 89% respectively.A positive correlation between US and HRCT findings were found (p < 0.001) whereas no correlation was found with chest radiographs and DLCO findings Positive association between US findings and DAS28-ESR, anti-CCP and RF (p<0.01 for each respectively) was found.Feasibility, represented by the mean time spent to perform the pulmonary US assessment was 7.8 minutes (± SD 1.2, range 6 to 10 minutes). CONCLUSIONS: Our results support the potential of US in detect accurately ILD in patients with RA and provide a rationale to consider it as a friendly screening tool to be implemented in early phases of the disease.
35487454 Th1 and Th17 cells are resistant towards T cell activation-induced downregulation of CD6. 2022 May BACKGROUND: The cell surface molecule CD6 is a modulator of T cell receptor (TCR) signaling. Recently, it has been reported that CD6 is downregulated on CD4+ T cells following T cell activation. This mechanism could limit the efficacy of anti-CD6 therapeutical antibodies. METHODS: We analyzed CD6 expression on activated and non-activated Th1 cells and Th17 cells by flow cytometry. RESULTS: Our experiments confirmed a significant downregulation of CD6 on IFNγ- and IL17-negative CD4+ T cells from healthy individuals and from patients with rheumatoid arthritis following T cell activation with anti-CD3 and anti-CD28 antibodies. In contrast, CD6 expression remained stable on activated Th17 cells and Th1 cells. CONCLUSIONS: Th1 and Th17 cells are resistant towards T cell activation-induced downregulation of CD6. These findings are relevant for the future development of CD6 targeting therapies and show that CD6 expression is differentially regulated in CD4+ T cell subsets.
35024385 Usefulness of cortical thickness ratio of the third metacarpal bone for prediction of majo 2022 Jun OBJECTIVE: Patients with rheumatoid arthritis (RA) are at high risk for osteoporotic fractures. We developed an index called the third metacarpal cortical thickness ratio (CTR), which reflects bone mineral density (BMD) in RA patients. A longitudinal study was conducted to verify the usefulness of CTR during the follow-up period. METHODS: Patients with RA who underwent dual energy X-ray absorptiometry (DXA) and hand X-ray simultaneously were monitored for disease activity and activities of daily living at 3-month intervals, and BMD and CTR were measured at 1-year intervals. Mean CTR during follow-up was tested for correlation with mean BMD at both the lumbar spine (LS) and femoral neck (FN) during follow-up. Correlations were examined, including other variants potentially correlated with BMD. The risk ratio of accidental major osteoporotic fractures (MOF) in the variance including CTR and BMD was evaluated. RESULTS: A total of 300 patients, 40 men and 260 women, were enrolled. Mean follow-up length was 49.6 months. CTR was significantly associated with BMD in FN using a multivariate model of linear regression analysis (p < 0.0001), whereas CTR was significantly associated with BMD in LS using only a univariate model (p < 0.01). The only variant with a significantly higher risk ratio for incident MOF was the presence of prevalent MOF. CTR and BMD did not show a significantly higher risk ratio using Cox regression analysis. CONCLUSION: CTR correlated significantly with BMD even during follow-up, especially in FN. However, CTR and BMD were not risk factors for major MOF.
34626791 Lipid scavenging macrophages and inflammation. 2022 Jan Macrophages are professional phagocytes, indispensable for maintenance of tissue homeostasis and integrity. Depending on their resident tissue, macrophages are exposed to highly diverse metabolic environments. Adapted to their niche, they can contribute to local metabolic turnover through metabolite uptake, conversion, storage and release. Disturbances in tissue homeostasis caused by infection, inflammation or damage dramatically alter the local milieu, impacting macrophage activation status and metabolism. In the case of persisting stimuli, defective macrophage responses ensue, which can promote tissue damage and disease. Especially relevant herein are disbalances in lipid rich environments, where macrophages are crucially involved in lipid uptake and turnover, preventing lipotoxicity. Lipid uptake is to a large extent facilitated by macrophage expressed scavenger receptors that are dynamically regulated and important in many metabolic diseases. Here, we review the receptors mediating lipid uptake and summarize recent findings on their role in health and disease. We further highlight the underlying pathways driving macrophage lipid acquisition and their impact on myeloid metabolic remodelling.
35134119 Effectiveness of baricitinib and tofacitinib compared to bDMARDs in RA: results from a coh 2022 Feb 3 OBJECTIVES: To describe the use of baricitinib and tofacitinib by Swedish rheumatoid arthritis (RA) patients and to compare their effectiveness with that of biological disease-modifying anti-rheumatic drugs (bDMARDs). METHODS: RA patients who initiated baricitinib [N = 1420], tofacitinib [N = 316], abatacept [N = 1050], interleukin-6 inhibitors (IL6i) [N = 849], rituximab [N = 1101] or tumour necrosis factor inhibitors (TNFi) [N = 6036] between January 2017 and November 2019 were followed for minimum one year, using data from several linked Swedish national registers. Proportions reaching good-EULAR-DAS28 response, HAQ-DI improvement above 0.2 units and CDAI remission were compared at one year, imputing discontinued treatments as "non-response". Additionally, we compared drug retention and changes in DAS28, HAQ-DI and CDAI from baseline to three months after treatment initiation. RESULTS: On average, baricitinib and particularly tofacitinib were initiated as later lines of therapy and more frequently as monotherapy compared with rituximab and TNFi. Adjusted one-year response proportions were consistently lower on TNFi compared with baricitinib, with differences of -4.3 percentage points (95% CI: -8.7-0.1) for good-EULAR response, -9.9 (-14.4 to -5.4) for HAQ-DI improvement, and -6.0 (-9.8 to -2.2) for CDAI remission. Comparisons with non-TNFi bDMARDs also favoured baricitinib, but not consistently. Treatment responses for tofacitinib were only marginally lower than those for baricitinib and generally similar to those of bDMARDs, with precision limited by low power. Comparisons of drug retention and changes in disease activity from baseline to three months supported the one-year findings. CONCLUSIONS: Baricitinib and tofacitinib showed at least equivalent effectiveness compared with bDMARDs after exploring several different effectiveness measures.
35558741 Causal Association Between Tea Consumption and Bone Health: A Mendelian Randomization Stud 2022 BACKGROUND: Much observational research reported that tea consumption decreases the risk of osteoarthritis (OA), rheumatoid arthritis (RA), and osteoporosis (OP) which are the three major bone disorders. However, the observed correlation is inconclusive. To determine the causal relationship between genetically predicted tea intake and OA, RA, and OP, we performed a two-sample Mendelian randomization (MR) study based on large samples. METHODS: The European population's genome-wide association meta-analysis (GWAS) dataset identified SNPs associated with tea consumption was obtained from Neale Lab's analysis of UK Biobank data that comprised 349,376 participants of European ancestry. We extracted genetic data for knee OA (17,885 controls and 4,462 cases), hip OA (50,898 controls and 12,625 cases), and RA (43,923 controls and 14,361 cases) from the UK Biobank and OP cases (93083 controls and 1,175 cases) from FinnGen Data Freeze 2. A MR study was conducted to examine the effect of selected single nucleotide polymorphisms (SNPs) and OA, RA, and OP risk. Several sensitivity analyses were performed with weighted median and inverse-variance weighted methods for estimating the causal effects. RESULTS: In this MR study, the genetically predicted per one cup increase of tea consumption was not associated with knee OA (OR 1.11,95% CI: 0.79-1.55) using IVW with random effect. Genetic predisposition to tea consumption was not associated with hip OA (OR: 1.20, 95% CI: 0.84-1.71), RA (OR: 1.24 95% CI: 0.81-1.91), and OP (OR: 1.11, 95% CI: 0.89, 1.39). Following the sensitivity analysis, there was no potential pleiotropy. CONCLUSION: According to our study, According to our study, there was no statistical power to confirm a causal relationship between tea consumption and the risk of knee OA, hip OA, RA, and OP.
35429914 RNA-binding protein hnRNP UL1 binds κB sites to attenuate NF-κB-mediated inflammation. 2022 May Heterogeneous nuclear ribonucleoproteins (hnRNPs), a family of RNA-binding proteins, play important roles in various biological processes. However, the roles of hnRNPs members in immunity and inflammation remain to be fully understood. By a functional screening for hnRNPs members in LPS-stimulated macrophage inflammatory response, we identified hnRNP UL1 as a negative regulator of NF-κB-mediated inflammation. hnRNP UL1 constrains NF-κB-triggered transcriptional expression of pro-inflammatory cytokines in response to innate stimuli. Perturbation of hnRNP UL1 enhanced pro-inflammatory cytokine production in macrophages. In vivo deficiency of hnRNP UL1 increased the pro-inflammatory cytokine production once challenged with LPS. Accordingly, the expression of hnRNP UL1 decreased in peripheral blood mononuclear cells of rheumatoid arthritis patients. Mechanistically, hnRNP UL1 competes with NF-κB to bind κB sites to constrain the magnitude and duration of inflammatory response. Meanwhile, the broadly and dynamically binding of hnRNP UL1 on the target genes' promoter during inflammatory response is unraveled. Our study adds new insight into the functions of hnRNPs in NF-κB-mediated inflammation, proposing a potential therapeutic strategy for controlling inflammatory autoimmune diseases.
35269726 Substance P, A Promising Therapeutic Target in Musculoskeletal Disorders. 2022 Feb 26 A large number of studies have focused on the role of substance P (SP) and the neurokinin-1 receptor (NK1R) in the pathogenesis of a variety of medical conditions. This review provides an overview of the role of the SP-NK1R pathway in the pathogenesis of musculoskeletal disorders and the evidence for its role as a therapeutic target for these disorders, which are major public health problems in most countries. To summarize, the brief involvement of SP may affect tendon healing in an acute injury setting. SP combined with an adequate conjugate can be a regenerative therapeutic option in osteoarthritis. The NK1R antagonist is a promising agent for tendinopathy, rheumatoid arthritis, and osteoarthritis. Research on the SP-NK1R pathway will be helpful for developing novel drugs for osteoporosis.