Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33942201 The characteristics and its contributing factors of refractory rheumatoid arthritis, view 2021 Oct OBJECTIVE: To explore the characteristics of refractory RA and its contributory factors based on the understanding of the rheumatologists of China. METHODS: A national cross-sectional survey was performed in 32 provinces across China, and 1381 rheumatologists were recruited. Information about the sociodemographic background, refractory RA characteristics, and contributory factors was collected using a pre-made questionnaire including fourteen single-choice and four multiple-choice questions, respectively. Each of the single-choice and multiple-choice question had several items. RESULTS: In response to the single-choice questions regarding the definition of refractory RA, 52.28% responded that "the 28 joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) > 5.1 with presence of signs suggestive of inflammatory disease" is characteristic of refractory RA, whereas 50.18% opined that "If target was not achieved with 2 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combined with 1 biological or 1 targeted synthetic DMARD (b/tsDMARD), over a total of 3~6 months" should be considered refractory RA. In addition, 39.32% rheumatologists were in favor of inability to taper glucocorticoids (GCs) ≤ 10mg prednisone or equivalent daily. Additional features considered characteristics of refractory RA were extra-articular manifestations (84.94%), interfering comorbidities (76.32%), and radiographic progression (71.83%). Among the contributory factors, 92.03% considered infection, and interstitial lung disease was chosen by 90.95%, vasculitis by 82.26%, osteoporosis by 70.67%, and fibromyalgia syndrome by 70.38%. CONCLUSIONS: Our survey has demonstrated a variety of concepts of refractory RA among the rheumatologists of China. Disease activity assessment, treatment options, interfering comorbidities, and radiological progression all were associated with the characteristics of refractory RA. Key Points • This study demonstrated the definition, characteristics, and contributing factors of refractory RA from the rheumatologists' views in China. • The clarification of the insights and concepts on refractory RA will help to make comprehensive guidelines to treat this disease, further improving prognosis and reducing the societal burdens of RA.
33356304 Proteomic Data Analysis for Differential Profiling of the Autoimmune Diseases SLE, RA, SS, 2021 Feb 5 Early and correct diagnosis of inflammatory rheumatic diseases (IRD) poses a clinical challenge due to the multifaceted nature of symptoms, which also may change over time. The aim of this study was to perform protein expression profiling of four systemic IRDs, systemic lupus erythematosus (SLE), ANCA-associated systemic vasculitis (SV), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), and healthy controls to identify candidate biomarker signatures for differential classification. A total of 316 serum samples collected from patients with SLE, RA, SS, or SV and from healthy controls were analyzed using 394-plex recombinant antibody microarrays. Differential protein expression profiling was examined using Wilcoxon signed rank test, and condensed biomarker panels were identified using advanced bioinformatics and state-of-the art classification algorithms to pinpoint signatures reflecting each disease (raw data set available at https://figshare.com/s/3bd3848a28ef6e7ae9a9.). In this study, we were able to classify the included individual IRDs with high accuracy, as demonstrated by the ROC area under the curve (ROC AUC) values ranging between 0.96 and 0.80. In addition, the groups of IRDs could be separated from healthy controls at an ROC AUC value of 0.94. Disease-specific candidate biomarker signatures and general autoimmune signature were identified, including several deregulated analytes. This study supports the rationale of using multiplexed affinity-based technologies to reflect the biological complexity of autoimmune diseases. A multiplexed approach for decoding multifactorial complex diseases, such as autoimmune diseases, will play a significant role for future diagnostic purposes, essential to prevent severe organ- and tissue-related damage.
34930943 The activation fragment of PAR2 is elevated in serum from patients with rheumatoid arthrit 2021 Dec 20 Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was developed targeting the 36-amino acid peptide that is cleaved and released after PAR2 activation (PRO-PAR2). Technical assay parameters including antibody specificity, intra- and inter-assay variation (CV%), linearity, accuracy, analyte stability and interference were evaluated. PRO-PAR2 release was confirmed after in vitro cleavage of PAR2 recombinant protein and treatment of human synovial explants with matriptase. Serum levels of 22 healthy individuals, 23 OA patients and 15 RA patients as well as a subset of RA patients treated with tocilizumab were evaluated. The PRO-PAR2 antibody was specific for the neo-epitope and intra-inter assay CV% were 6.4% and 5.8% respectively. In vitro cleavage and matriptase treated explants showed increased PRO-PAR2 levels compared to controls. In serum, PRO-PAR2 levels were increased in RA patients and decreased in RA patients treated with tocilizumab. In conclusion, PRO-PAR2 may be a potential biomarker for monitoring RA disease and pharmacodynamics of treatment.
32203571 Testing a self-determination theory-based process model of physical activity behavior chan 2021 Mar 16 Physical inactivity is prevalent in rheumatoid arthritis (RA) patients, increasing the risk of poor physical health and compromised well-being. Interventions are therefore required to support physical activity (PA) behavior change in this population. This study examined whether a self-determination theory (SDT) based exercise intervention for people with RA, increased autonomous motivation for PA and in turn, moderate-to-vigorous PA (MVPA) and subjective vitality RA patients (n = 115) were randomized to a 3-month SDT-based psychological intervention + RA-tailored exercise program (experimental group, n = 59) or a RA-tailored exercise program only (control group, n = 56). During the program, the SDT-based intervention group received one-on-one consultations with a PA advisor trained in delivering strategies to promote autonomous motivation for PA. Well-established questionnaires assessed autonomous and controlled motivation for PA, MVPA (min/week), and subjective vitality at baseline (T1) and 3 months (T2). Path analysis examined the hypothesized theoretical process model. The model demonstrated an excellent fit to the data (n = 70, χ2 (26) = 28.69, p = .33, comparative fit index = 0.99, root square mean error of approximation = 0.04). The intervention corresponded to higher autonomous motivation and lower controlled motivation for PA at T2, after controlling for T1 autonomous and controlled motivation. In turn, changes in autonomous motivation from T1 to T2 significantly positively predicted changes in MVPA and subjective vitality. Results suggest an SDT based psychological intervention comprising autonomy-supportive strategies for PA predicted greater reported autonomous reasons for PA in RA patients participating in a tailored 3-month exercise program. Increased autonomous motivation linked to increased engagement in MVPA and feelings of vitality in these patients.
34732237 Observation of the curative effect of Guizhi-Shaoyao-Zhimu decoction combined with methotr 2021 Nov 3 BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with the primary clinical symptoms of joint swelling and pain. Early detection of erosion and synovial inflammation at an active stage resulting from RA can prevent damage to the joints and activity restriction. However, there are still many patients who do not respond to these treatments; the development of newer, safer drugs is urgently needed. Compared to Western medicine, Guizhi-Shaoyao-Zhimu decoction has equal or higher efficacy and safety for RA patients. With the widespread use of musculoskeletal ultrasound (MSUS), this technology holds great value for the degree of joint damage in RA patients, guiding the clinical selection of treatments, and assessing of prognosis. Therefore, we designed a double-blinded randomized controlled clinical trial to measure the safety and efficacy of Guizhi-Shaoyao-Zhimu decoction in treating early-stage RA using MSUS. METHODS: This study is a randomized, double-blinded, parallel group, placebo-controlled trial. A total of 152 adult participants with early RA will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be Guizhi-Shaoyao-Zhimu decoction plus the conventional medicine methotrexate and the control intervention will be placebo plus the conventional drug methotrexate for 3 months. In addition, both groups will receive folic acid during treatment to prevent side effects from methotrexate. The primary outcomes are the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hepatic and renal function, visual analog scale, disease activity score in 28 joints, measurement scale for TCM symptoms, and 7-joint ultrasound score. DISCUSSION: We designed this double-blinded randomized controlled clinical trial to evaluate the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in RA patients using MSUS. The results of this trial may provide insights into how to improve the clinical symptoms of RA patients and delay further joint destruction. We hope that this trial may provide preliminary evidence of the efficacy of Guizhi-Shaoyao-Zhimu decoction in treating RA patients and that these results aid researchers, practitioners, and patients alike. AIM: The main aim of the study is to clarify the efficacy and safety of Guizhi-Shaoyao-Zhimu decoction in patients with early RA. TRIAL REGISTRATION: Chinese Clinical Trials Register ChiCTR2000036141 . Registered on 21 August 2020 (retroactively registered).
34842032 CT-P13 SC for the treatment of rheumatoid arthritis. 2022 Jan INTRODUCTION: Management of Rheumatoid Arthritis (RA) has improved following the implementation of early intensive treat to target recommendations and the availability of different biologicals. Most experience is with TNF blockers, but challenges remain in the efficacy/safety balance, immunogenicity, and long-term drug survival as well as availability and affordability despite the introduction of biosimilars. AREA COVERED: We provide an overview of the development of CT-P13 SC based on infliximab biosimilar CT-P13 IV. The one-year pivotal phase I/III trial in RA showed CT-P13 120 mg SC fixed dose to have favorable pharmacokinetics compared to CT-P13 IV classical weight adapted dosing, similar to lower anti-drug antibodies, similar safety and non-inferiority for efficacy at 6 months. EXPERT OPINION: CT-P13 SC is an additional option in RA treatment and by extension for other inflammatory diseases as Inflammatory Bowel Disease. This new way of administration has the potential to improve long-term drug survival of infliximab, improve patient outcomes, and patient comfort.
33385864 The prevalence and risk factors of sarcopenia in rheumatoid arthritis patients: A systemat 2021 Feb BACKGROUND: Sarcopenia is an ever-increasingly recognized entity in aging or chronically-ill individuals. A recent surge of researches came out on sarcopenia in rheumatoid arthritis (RA). However, the results varied widely. We tried to assess the prevalence of and associated factors with sarcopenia in patients with RA. METHODS: We searched the investigations dealing with the prevalence of and associated factors with sarcopenia in RA from PubMed, EMBASE, CENTRAL, EBSCOhost, Airiti Library, CEPS, CNKI and J-STAGE from the inception to January 11, 2020. Effects regarding prevalence and associated factors were extracted and evaluated by random-effects model. Sensitivity analysis was also performed. RESULTS: Seventeen studies containing 3,140 RA subjects were identified. After exclusion of outliers, the pooled prevalence of sarcopenia was 31%. Neither ongoing-study districts nor diagnostic modalities affected prevalence significantly. Any associated factors being mentioned in at least two publications were analyzed, yielding functional limitation (Steinbrocker stage III/IV), high CRP and RF seropositivity as the significant risk factors. Based on disease durations, we carried out meta-regression and found DAS28 and HAQ are predictive models. There was no alteration in the interpretation of results from sensitivity analysis after removal of any studies skewed in sampling distribution. CONCLUSIONS: The prevalence of sarcopenia in patients with RA is high, compared to that in general counterparts. Disease duration rather than age, residing area or diagnostic modalities influences sarcopenia development; DAS28 and HAQ predict occurrence. High index of suspicion to facilitate early detection of sarcopenia in RA patients is important.
33221617 Comparison between 3-point Dixon- and CHESS-based OMERACT-recommended MRI protocols in han 2021 Jan PURPOSE: To compare fat suppression effectiveness, image quality and disease activity scores between MRI protocols based on the Dixon method and the Chemical Shift Selective (CHESS) technique in hands of patients with suspicion of early rheumatoid arthritis (RA). METHOD: Both hands of 28 patients (19 women; mean age 45.2 years old) with suspicion of early RA were prospectively imaged with Dixon- and CHESS-based OMERACT recommended protocols at 1.5 T including fat-suppressed T2-weighted and contrast-enhanced T1-weighted imaging. Two radiologists (R1/R2) separately assessed effectiveness of fat suppression and determined RAMRIS scores woth the Dixon- and CHESS-based protocols. R1 repeated the RAMRIS scoring and measured contrast-to-noise ratios (CNRs) on Dixon and CHESS images. Statistics included 2-way ANOVA test for the comparison of CNRs and Bland-Altman methodology for inter-technique and intra-observer agreement (p < 0.05). RESULTS: Fat suppression failure occurred in up to 1 patient with the Dixon- and 25 patients with the CHESS-based protocols. CNRs were significantly higher on T1-weighted and lower on T2-weighted Dixon images than on the corresponding CHESS images (p ≤ 0.042). Median bias of the difference between Dixon- and CHESS-based RAMRIS scores was not significantly different from 0 (-0.8 to +1.0 and -1.1 to +1.4 for R1/R2). Median bias of the difference between RAMRIS scores at first and second readings was significantly different from 0 with the CHESS-based protocols (-0.8 to +1.7) but not with the Dixon-based protocols (+0.0 to +1.0). CONCLUSIONS: Dixon sequences yield more effective fat suppression and more reproducible RAMRIS scoring than CHESS sequences in hands with suspicion of early RA.
33559338 Outcomes of a Mobile App to Monitor Patient-Reported Outcomes in Rheumatoid Arthritis: A R 2021 Aug OBJECTIVE: To examine the effects of a smartphone application (app) to monitor longitudinal electronic patient-reported outcomes (ePROs) on patient satisfaction and disease activity in patients with rheumatoid arthritis (RA). METHODS: We conducted a 6-month randomized controlled trial of care coordination along with an app (intervention) versus care coordination alone (control) in 191 RA patients. Participants in the intervention group were prompted to provide information daily using ePROs. In both the intervention and control groups, a care coordinator contacted participants at 6 and 18 weeks to assess for flares. The main outcome measures were the global satisfaction score from the Treatment Satisfaction Questionnaire for Medication (TSQM), the score from the Perceived Efficacy in Patient-Physician Interactions (PEPPI) Questionnaire, and the Clinical Disease Activity Index (CDAI) score. RESULTS: Groups were similar at baseline. The median TSQM score at 6 months was 83.3 in both groups, and the median PEPPI score at 6 months was 50 in both groups. The median CDAI score at 6 months was 8 in the intervention group versus 10 in the control group. No statistically significant group differences in the medians of TSQM, PEPPI, or CDAI scores at 6 months were detected. Of the 67 intervention participants who completed the exit survey, 90% rated their likelihood of recommending the app as ≥7 of 10. Of the 11 physicians who completed the exit survey, 73% agreed/strongly agreed that they wanted to continue offering the app to patients. CONCLUSION: A mobile app designed to collect ePRO data on RA symptoms did not significantly improve patient satisfaction or disease activity compared to care coordination alone. However, both patients and physicians reported positive experiences with the app.
33295139 Lifetime Risks, Life Expectancy, and Health Care Expenditures for Rheumatoid Arthritis: A 2021 May OBJECTIVE: This study was undertaken to estimate the cumulative incidence rate of rheumatoid arthritis (RA) in the Taiwanese population ages 16-84 years, and life expectancy, loss of life expectancy, and lifetime health care expenditures for incident RA in Taiwan after 2003, when biologics began to be prescribed. METHODS: We obtained all claims data for the period 1999 to 2016 from the National Health Insurance program of Taiwan, and validated the data against the Catastrophic Illness Registry to establish the study cohort. We estimated the survival function for RA and extrapolated to lifetime using a rolling-over algorithm. For every RA case, we simulated sex-, age-, and calendar year-matched referents from vital statistics and estimated their life expectancy. The difference between the life expectancy of the referent and the life expectancy of the RA patient was the loss of life expectancy for the RA patient. Average monthly health care expenditures were multiplied by the corresponding survival rates and summed up throughout the lifetime to calculate the lifetime health care expenditures. RESULTS: A total of 29,352 new RA cases were identified during 2003-2016. There was a decreasing trend in cumulative incidence rate in those ages 16-84 for both sexes. Mean life expectancy after diagnosis of RA was 26.3 years, and mean lifetime cost was $72,953. RA patients had a mean loss of life expectancy of 4.97 years. Women with RA survived 1-2 years longer than men with RA of the same age, which resulted in higher lifetime expenditures for the former. Since the life expectancy for women in Taiwan was 6-7 years higher than that for men, the loss of life expectancy for women with RA was higher than that for men with RA. Annual health care expenditures were similar for both sexes. CONCLUSION: Our findings indicate that since biologics became available, RA patients have lived longer and had higher lifetime expenditures, which should be monitored and evaluated for cost-effectiveness.
34424413 Incidence of and risk factors for spondylolisthesis, scoliosis, and vertebral fracture in 2022 Jan INTRODUCTION: Although lumbar lesions such as spondylolisthesis, scoliosis, and vertebral fracture are not specific to rheumatoid arthritis (RA), the prevalence is high in RA patients. However, no longitudinal study has evaluated lumbar lesions in RA. This study aimed to investigate the incidence of and risk factors for lumbar lesions in RA by a prospective longitudinal cohort study. MATERIALS AND METHODS: The study cohort comprised 110 patients with RA from the 'analysis of factors for RA spinal disorders (AFFORD)' study who completed the secondary survey at a single orthopaedic outpatient RA clinic. Radiological examination included standing radiographs and magnetic resonance imaging (MRI) of the lumbar spine. New development of spondylolisthesis, scoliosis, and vertebral fracture were assessed between baseline and secondary survey. RESULTS: The incidences of spondylolisthesis, scoliosis, and vertebral fracture were 42%, 16%, and 12%, respectively, during a mean follow-up of 7 years. The independent risk factor for de novo scoliosis was poor control of RA (adjusted odds ratio [aOR] 4.81, p = 0.011), while the independent risk factors for new vertebral fracture was use of glucocorticoid at secondary survey (aOR 14.87, p = 0.012). Patients with de novo scoliosis exhibited more severe low back pain and lower quality of life than those without. CONCLUSION: The incidence of scoliosis was related in patients with poor control of RA, while new vertebral fracture was more common in patients with use of glucocorticoid. Control of disease activity might be important in preventing radiological lumbar disorders in RA.
34161227 Dietary habits in patients with fibromyalgia: a cross-sectional study. 2021 May OBJECTIVES: To the scarce information on dietary habits in fibromyalgia (FM), it is added that there are no comparative studies with other rheumatic diseases. The objective of this study was to characterise the dietary habits of patients with FM by comparing, for the first time, with healthy controls (HC) and rheumatoid arthritis (RA). METHODS: This cross-sectional, observational study was based on data obtained from the Dietfibrom project for FM and from the IMID Consortium for RA and HC. All participants completed a food frequency questionnaire evaluating their weekly dietary intake of main food groups. The three cohorts were compared using a multiple logistic regression model adjusted for age, sex, and body mass index. RESULTS: After quality control, n=287 FM, n=1,983 HC and n=1,942 RA patients were analysed. We found that FM had a profound impact in the diet compared to HC, reducing the consumption of dairy (OR=0.32, p<0.0001), bread and/or whole grain cereals (OR=0.59, p=0.0006), fresh fruit (OR=0.66, P=0.008), and fish (OR=0.64, p=0.002). These same four food groups were also significantly reduced in FM patients in comparison to RA patients (p<0.0005 in all cases). Additionally, a lower consumption of pasta, rice and/or potatoes was also observed in FM compared to RA (OR=0.72, p=0.028). CONCLUSIONS: The present cross-sectional study shows that FM is associated to a significant change in the normal dietary patterns. These results underscore the importance of diet in this prevalent disease and are a warning of the potential long-range effects of a deficient nutritional status.
32995835 Anti-carbamylated protein antibodies in premenopausal rheumatoid arthritis women: relation 2021 Mar 2 OBJECTIVES: Anti-carbamylated protein antibodies (anti-CarP Abs) are present in patients with RA, however, their association with bone loss is not confirmed. The purpose of this study was to determine the relation between the serum level of anti-CarP Abs in premenopausal RA women and disease activity and bone loss. METHODS: This case-control study was conducted on 48 premenopausal women with RA and 48 matched healthy premenopausal women. All RA women were subjected to clinical examination, disease activity assessment using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), functional assessment using the HAQ, physical activity assessment using the International Physical Activity Questionnaire (IPAQ), fatigue assessment using the Modified Fatigue Impact Scale (MFIS), serological tests as well as anti-CarP Abs using ELISA. Moreover, the BMD was measured by DXA and plain X-ray of both hands was done to assess juxta-articular osteopenia and erosions. RESULTS: The anti-CarP Abs level was significantly higher in RA patients than in healthy controls. The serum level of anti-CarP Abs had a significant positive correlation with the RA DAS28, CDAI, HAQ, MFIS and original Sharp score, while a significant negative correlation was present with the IPAQ. Anti-CarP Abs were negatively correlated with either spine BMD or Z-score and positively correlated with the original Sharp score. CONCLUSION: Anti-CarP Abs were higher in premenopausal RA women compared with older and BMI matched healthy women. Anti-CarP Abs are associated with higher RA disease activity, increased disability and fatigability and decreased physical activity. Moreover, anti-CarP Abs are associated with systemic trabecular bone loss as well as local bone loss.
33625045 Glucocorticoid and opioid use in rheumatoid arthritis management. 2021 May 1 PURPOSE OF REVIEW: Glucocorticoids and opioids are longstanding, common treatments for rheumatoid arthritis (RA) symptoms. High-quality clinical trials have established that glucocorticoids improve outcomes in RA, but debate continues as to whether their benefits outweigh their risks. We reviewed recent studies on patterns of glucocorticoid and opioid prescribing in RA, and associated harms. RECENT FINDINGS: At present, a large proportion of RA patients remain on glucocorticoids and/or opioids long-term. Likelihood and risk of both glucocorticoid and opioid exposure vary across the population, and are influenced by provider factors. Opioids are also associated with delays in disease-modifying treatment initiation. Recent evidence increasingly demonstrates toxicity associated with even low-dose glucocorticoids (≤7.5 mg/day). Up to two-thirds of RA patients may be able to discontinue chronic low-dose glucocorticoids without flare or adrenal insufficiency. These new data have led to changes in clinical practice guidelines for glucocorticoid use in RA. SUMMARY: Although low-dose and short-term glucocorticoid use is extremely common and effective in RA management, increasing evidence of toxicity has led experts to begin recommending that such exposure be minimized. Despite a lack of data to suggest opioids improve RA disease activity, they are used commonly, continued long-term, and associated with delayed effective therapy.
32556934 PON-1 haplotype (-108C>T, L55M, and Q192R) modulates the serum levels and activity PONase 2021 Feb INTRODUCTION/OBJECTIVE: Paraoxonase 1 (PON1) promotes antioxidant and antiatherogenic activity related to the hydrolysis of oxidized lipids of low-density lipoproteins. In rheumatoid arthritis (RA) patients, it has been reported that low PON1 activity is related to an impaired lipid profile, increasing cardiovascular risk (CVR). The goal of this study was to analyze the effect of common PON1 polymorphisms and haplotypes on enzymatic activity, PON1 serum levels (PON1s), and lipid parameters related to atherogenic profile in RA patients. METHODS: A cross-sectional study was carried out on 250 Mexican patients with RA. The lipid profile was determined by colorimetric tests. The PON1 activity (CMPAase) was measured by spectrophotometry. The levels of PON1s were determined by ELISA, and the polymorphisms in the PON-1 gene (-108C>T, L55M, and Q192R) were genotyped by the PCR-RFLP method. The haplotypes were estimated and statistical analysis was performed. RESULTS: The median of the CMPAase activity and PON1 levels was 13.91 U/mL and 24.75 ng/mL, respectively. The CMPAase activity was significantly lower in carriers of -108TT and 192QQ genotypes (β = - 4.09, P = 0.001 and β = - 3.73, P = 0.002, respectively); moreover, the PON1 levels were lower in 192Q allele carriers (P < 0.01). The TLQ haplotype was associated with CMPAase activity < 13.91 U/mL (OR = 2.29, P < 0.001), as well as with levels of PON1s < 24.75 ng/mL (OR = 1.65, P = 0.017). In this study, the CMPAase activity (< 13.91 U/mL) showed a positive association with lower levels of high-density lipoprotein cholesterol (HDL-c; < 40/50 mg/dL), and with a triglycerides/HDL-c ratio > 3%, and a total cholesterol/HDL-c ratio > 4.5/5%, all representatives of an atherogenic risk lipid profile. CONCLUSIONS: PON1 polymorphisms modulate the CMPAase activity and PON1 levels in Mexican patients with RA. The CMPAase activity < 13.91 U/mL is associated with an atherogenic lipid profile, independently of inflammation markers and treatment with anti-rheumatic drugs. Key Points •The haplotype TLQ is a marker for low PONase activity in rheumatoid arthritis. •The haplotype TLQ is a marker for low PON1 serum levels in rheumatoid arthritis. •The enzymatic PON1 activity represents the best marker for an atherogenic lipid profile in rheumatoid arthritis, in comparison with PON1 levels. •The haplotype TLQ is a marker of low PON1 activity, levels of PON1s, and atherogenic lipid profile, independent of treatment therapy in rheumatoid arthritis.
34397713 The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone 2021 Jul 30 Baricitinib is a Janus kinase (JAK) inhibitor that selectively blocks against JAK1 and JAK2 signaling. This study aimed to determine the effect of baricitinib on disease activity based on musculoskeletal ultrasound in patients with rheumatoid arthritis (RA).A total of 20 patients with RA receiving baricitinib for 24 weeks were assessed. Ultrasound scores of gray scale and power Doppler synovitis, joint effusion, and bone erosion in each patient were assessed between baseline and 24 weeks for 27 affected joints. Disease activity in RA was evaluated using the disease activity score for 28-joint count with erythrocyte sediment rate (DAS28-ESR), simplified disease activity index (SDAI), and clinical disease activity index (CDAI).Treatment with baricitinib for 12 weeks and 24 weeks significantly decreased disease activity composites such as DAS28-ESR, SDAI, and CDAI (P < .001 for all). Treatment with baricitinib for 24 weeks improved ultrasound-detected gray-scale and power Doppler synovitis and joint effusion compared to baseline (P = .002, P = .030, and P = .002, respectively). Bone erosion scores were not different between baseline and 24 weeks (P = .317). There were no differences in ultrasound abnormalities for improvement based on DAS28-ESR. Changes in power Doppler score were significantly associated with changes in DAS28-ESR (β = 0.590, P = .044), but not SDAI and CDAI.This study demonstrates that baricitinib treatment has a favorable effect on ultrasound-detected abnormalities including synovitis and bone erosion in patients with RA.
33834280 "Platelet-rich plasma holds promise in management of rheumatoid arthritis"-systematic revi 2021 Nov The treatment of rheumatoid arthritis (RA) has been closely evolving with an understanding of disease pathogenesis with disease modifying anti-rheumatoid drugs (DMARDS) and Biologic DMARDS being the main stay. platelet rich plasma (PRP) has been the center of research in many specialties in the past decade. Its ability to stop and reverse inflammation have attracted researchers to try PRP in RA. A systematic review of studies on PRP in RA is lacking. The study protocol was prospectively registered in PROSPERO. Detailed search of Cochrane, Scopus, Medline, Embase, and Web of science databases were made to identify the relevant articles till Sep 2020 following Cochrane and PRISMA guidelines. Number of subjects, Animal model used, cell lines used for the study, method of induction of arthritis, PRP dose, concentration used, frequency of administration and clinical, histologic, and molecular changes from baseline following PRP use were extracted and analysed. Eight studies were included for the review. Four of these were in-vitro studies. Two were exclusive animal studies. One study analysed the effects of PRP in RA in both animal models (mice) and Hela cell lines. One study was a report of a series of patients of resistant RA treated with PRP. In the in vitro studies while platelets increase the migration and invasion of RA-FLS, they suppressed the inflammation on the whole. Available animal studies and the Human study have shown encouraging results. There has been no evidence of exacerbation of inflammation in these studies. The quantity and quality of literature on the effects of PRP in treating joint pathologies in RA is limited. Preclinical studies show decrease in disease activity with good safety profile. Invitro studies show suppression of inflammation. Thus, the available literature is encouraging towards the use of PRP in RA. Larger trials and molecular studies to understand the exact role of platelets in disease pathogenesis and treatment mechanisms are needed to decide the future course of PRP in RA.
34524814 A Fast-Responsive OFF-ON Near-Infrared-II Fluorescent Probe for In Vivo Detection of Hypoc 2021 Sep 28 Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease, and its etiology is closely related to the overproduction of hypochlorous acid (HClO). However, early detection of RA using an activatable near-infrared-II (NIR-II, 1000-1700 nm) fluorescent probe remains challenging. Herein, we first report an "OFF-ON" NIR-II fluorescent probe named PTA (phenothiazine triphenylamine) for imaging HClO in deep-seated early RA. Electron-rich phenothiazine in the core of PTA was utilized as both an HClO-recognition moiety and a precursor of electron acceptors, displaying a typical donor-acceptor-donor structure with excellent NIR-II emission at 936/1237 nm once reacted with HClO. The probe PTA exhibited good water solubility, high photostability, and rapid response capability toward HClO within 30 s. Moreover, it was able to sensitively and specifically detect exogenous and endogenous HClO in living cells in both visible and NIR-II windows. Notably, PTA enabled the sensitive and rapid visualization of HClO generation in an inflammatory RA mouse model, showing a 4.3-fold higher NIR-II fluorescence intensity than that in normal hindlimb joints. These results demonstrate that PTA holds great promise as a robust platform for diagnosis of HOCl-mediated inflammatory disorders.
34428765 Celastrol Exerts Cardioprotective Effect in Rheumatoid Arthritis by Inhibiting TLR2/HMGB1 2021 OBJECTIVE: Rheumatoid arthritis (RA) is a kind of chronic inflammatory disease characterized by the release of inflammatory cytokines and cardiomyocyte apoptosis, which lead to increased riskfor heart diseases. This study aims to explore the possible effect and mechanism of Celastrol on RA induced cardiac impairments in rats. METHODS: Collagen induced RA wistar rat models (CIA) were established for the measurement on secondary foot swelling degree, polyarthritis index score, spleen and thymus index. Pathological morphology was observed using H&E staining. Heart fibrosis was measured after Sirius red staining, while cell apoptosis was determined by TUNEL staining. For in vitro experiments, rat cardiomyocytes were isolated to determine the inflammatory cytokine secretion and cell apoptosis using ELISA and flow cytometry, respectively. Protein expressions of related index and autophagy were detected by Western blot and immunofluorescence. RESULTS: CIA rat model was successfully established and characterized by severe secondary foot swelling degree, and increased polyarthritis index score and spleen and thymus index. Synovial hyperplasia, disordered cardiomyocytes, cell infiltration and fibrosis were also observed in CIA rat model. Compared with CIA model, Celastrol treatment could suppress the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β, as well as inhibiting the expressions of Bax, cleaved caspase3, collagen I, collagen III and α-SMA. In addition to that, Celastrol treatment can attenuate cell apoptosis and fibrosis of cardiomyocytes and elevate Bcl-2 expression. RA induced cell autophagy can be suppressed by Celastrol through inhibiting the activation of TLR2/HMGB1 signal pathway. CONCLUSION: Celastrol can regulate TLR2/HMGB1 signal pathway to suppress autophagy and therefore exert cardioprotective effect in RA.
33258552 In Utero and Early Life Exposure to the Great Chinese Famine and Risk of Rheumatoid Arthri 2021 Apr OBJECTIVE: To investigate whether early life exposure to the Great Chinese Famine of 1959-1961 is associated with the risk of RA development in adulthood. METHODS: This study included 101,510 participants who were enrolled in the Kailuan Study in 2006. RA cases were confirmed by medical record review. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for RA according to famine exposure status (exposed in utero or between ages 0 and 3 years, between ages 3 and 6 years, or at age 6 years or older), in comparison to participants born after 1961 who were not exposed to famine. RESULTS: During 12 years of follow-up (2006-2018), we identified 187 RA cases. Individuals exposed to famine in utero or between ages 0 and 3 years had a higher prevalence of RA relative to other groups (0.2-0.35% versus 0.08-0.20%). After adjustment for potential confounders, the OR for RA was 2.95 (95% CI 1.55-5.59) for individuals exposed in utero, 4.53 (95% CI 2.72-7.54) for those exposed between ages 0 and 3 years, 2.55 (95% CI 1.43-4.57) for those exposed between ages 3 and 6 years, and 2.72 (95% CI 1.70-4.36) for those exposed at age 6 years or older versus individuals born after 1961. Similar associations with the risk of RA were observed for men and women when subjects were stratified by sex (P for interaction = 0.89). CONCLUSION: Individuals exposed to famine in utero or in early childhood (between ages 0 and 3 years) were more likely to develop RA in adulthood, highlighting the importance of early life as a vulnerable developmental period.