Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
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31533820 | Fluorescence optical imaging for treatment monitoring in patients with early and active rh | 2019 Sep 18 | BACKGROUND: Fluorescence optical imaging (FOI) enables visualization of inflammation in the hands in rheumatic joint diseases with currently a lack of long-term follow-up studies. OBJECTIVE: To investigate FOI for treatment monitoring in a homogenous cohort of patients with early (disease duration < 2 years) and active (DAS28 > 3.2) RA over a period of 12 months. METHODS: Thirty-five RA patients (24 (68.6%) females, mean age 53.3 years (SD 13.6)) were investigated clinically by DAS28, tender joint count (TJC) and swollen joint count (SJC) and by FOI in phases 1-3 and PrimaVistaMode (PVM) before therapy change and after 12 months. The FOI activity score (FOIAS) was calculated based on individual joint scores from 0 to 3 in 30 joints per patient, adding up to a sum score (0-90). RESULTS: We found a statistically significant reduction of FOIAS in phase 1 from baseline (median 5.0, IQR 24.96) to follow-up (median 1.0, IQR 4.0) in all patients (p = 0.0045), both in responders and non-responders according to EULAR response criteria by DAS28. Statistically significant reductions over 12 months were found for median DAS28(ESR) 5.61 to 3.31, TJC 7.0 to 1.0, and SJC 5.0 to 1.0 (each p <  0.001). No statistically significant correlations were detected between the FOIAS change in phase 1 and DAS28(ESR), TJC, or SJC. Correlations between the other phases and clinical outcomes were weak to moderate. CONCLUSION: Reduced early enhancement in FOI phase 1 can be observed in clinically responding and non-responding early RA patients under treatment. Regarding potential marker performance, FOI probably shows a reduction of inflammation more objectively. | |
31120393 | Immunometabolism: an overview and therapeutic prospects in autoimmune diseases. | 2019 Jun | Metabolism is a critical immune regulator under physiologic and pathologic conditions. Culminating evidence has disentangled the contribution of distinct metabolic pathways, namely glucolysis, pentose phosphate, fatty acid oxidation, glutaminolysis, Krebs cycle and oxidative phosphorylation, in modulating innate and adaptive immune cells based on their activation/differentiation state. Metabolic aberrations and changes in the intracellular levels of specific metabolites are linked to the inflammatory phenotype of immune cells implicated in autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and diabetes. Notably, targeting metabolism such as the mTOR by rapamycin, hexokinase by 2-deoxy-D-glucose, AMP-activated protein kinase by metformin, may be used to ameliorate autoimmune inflammation. Accordingly, research in immunometabolism is expected to offer novel opportunities for monitoring and treating immune-mediated diseases. | |
30815278 | Associations between antenatal prednisone exposure and long-term cortisol and cortisone co | 2019 | OBJECTIVES: To identify whether children with antenatal prednisone exposure have chronically elevated cortisol and cortisone concentrations, an altered body composition or higher blood pressure. In addition, to identify whether maternal rheumatoid arthritis disease (RA) activity is associated with these alterations. METHODS: In this prospective study, 56 children (mean age=10.0 years) with and 61 children (mean age=9.6 years) without antenatal prednisone exposure, born to women with RA, were included. Hair cortisol and cortisone were analysed using liquid chromatography-tandem mass spectrometry. Linear regression models were built to analyse differences between the two groups, corrected for relevant covariates. Hair cortisol concentrations were also compared between the study population and an age-matched healthy reference group(n=150 children, mean age=9.8 years). RESULTS: Hair cortisol and cortisone concentrations were similar in children with and without antenatal prednisone exposure (median cortisol 1.14 pg/mg (IQR 0.67-1.75) and 1.15 pg/mg (IQR 0.65-2.21) and median cortisone 6.76 pg/mg (IQR 5.42-8.86) and 7.40 pg/mg (IQR 5.39-10.73), respectively). Antenatal prednisone exposure and maternal RA disease activity were also not associated with body composition or blood pressure. Hair cortisol concentrations were not different in children born to mothers with RA compared with children from the reference group. CONCLUSION: This, in its kind, large and unique long-term prospective study demonstrates that low-dose antenatal prednisone exposure and maternal RA disease activity are not associated with negative consequences in prepubertal childhood. The findings of this study are reassuring and support the assumption that low-dose maternal prednisone use during pregnancy is safe for the offspring, at least until the age of approximately 10 years. | |
31547746 | Value of contrast-enhanced ultrasound for detection of synovial vascularity in experimenta | 2019 Nov | OBJECTIVE: This study aimed to examine the associations between contrast-enhanced ultrasound (CEUS) imaging and synovial hypervascularity and synovitis score in a rabbit model of antigen-induced arthritis (AIA), compared with power Doppler ultrasound (PDUS). METHODS: We investigated 50 knee joints in 25 AIA rabbits (AIA group), and 10 knee joints in five sham-injected rabbits (control group). PDUS and CEUS images were evaluated at the 8(th) week. Ultrasound-guided synovial biopsies were targeted in the area with hypervascularity, and synovial microvessel density (MVD) was evaluated by immunohistochemical staining of CD31. RESULTS: The PDUS score was significantly higher in the AIA group (2.61 ± 0.78) compared with the control group (0.50 ± 0.53). CEUS in the AIA group revealed a fast-in/slow-out pattern of contrast enhancement. MVD revealed by CD31+ vessel count and the synovitis score were significantly higher in the AIA group compared with the control group. In the AIA group, CEUS findings showed a better correlation with MVD revealed by CD31+ and synovitis score than PDUS findings. CONCLUSION: CEUS is superior to PDUS for estimating synovial hypervascularity and hyperplasia in experimental rheumatoid arthritis. | |
30860321 | [Inflammatory arthritides pathotypes]. | 2019 Mar 6 | The pathophysiology of the inflammatory arthritides (IA) is complex and the result of interactions between genetic and environmental factors, leading to -in the case of seropositive rheumatoid arthritis-a breach of immune tolerance and subsequent development of joint and systemic manifestations. Regardless of the exact site of the initial immune dysregulation, the synovial membrane is the main target of IA. The heterogeneity of the clinical phenotypes is even more evident on the histological level (pathotypes), which in turn renders research on disease mechanisms more complicated. This article focusses on the various pathotypes of IA. | |
33328025 | Craving for menthol sweets: a case report. | 2020 Oct | We describe a case of craving for menthol sweets in a 53-year-old woman with excessive consumption of menthol sweets (100Â units/day). She was admitted with a history of rheumatoid arthritis, obesity, anxiety associated with onychophagia and pinching of the skin. Organic disorders were ruled out with paraclinical tests and in-hospital treatment was administered. At discharge, the patient's condition was stable, but because of exacerbated pain due to the rheumatological disease, she presented depressive symptoms, requiring her medication to be adjusted. CONCLUSIONS: The "food craving" and anxiety present pathophysiological similarities. Mints have different mechanisms or ways in which they can counteract or control these symptoms, including an increase in serotonin, binding to GABA-A receptors and stimulation of the nicotinic receptor in nerve cells. | |
31492495 | miR-138 activates NF-κB signaling and PGRN to promote rheumatoid arthritis via regulating | 2019 Oct 29 | BACKGROUND: Rheumatoid arthritis (RA) is a common immune-related disease worldwide, which is characterized by impaired fibroblast-like synoviocytes (FLS) proliferation and increased release of inflammatory cytokines. Unfortunately, the detailed mechanism by which miR-138-modulated rheumatoid arthritis has not been fully understood. METHODS: RT-qPCR was used to examined mRNA level of various genes and western blot was utilized to probe protein level of acetylated H3, p-p62 and IκBα. For cytokines detection, we used ELISA method to measure the extracellular level of these cytokines. Bioinformatic tool and dual-luciferase reporter assay were employed to predict and confirm the downstream target of miR-138. RESULTS: miR-138 was upregulated in serum and synovial tissues of RA patients. Moreover, Increased miR-138 was observed in LPS-treated FLS cells. HDAC4 was shown as the direct target of miR-138 and could be negatively regulated by miR-138. miR-138 and HDAC4 were involved in RA-related inflammatory cytokines release of FLS cells. Next, we revealed NF-κB and PGRN were significantly modulated by HDAC4 and miR-138 in an acetylation-dependent manner. More importantly, IκBα depletion and PGRN overexpression had the ability to rescue miR-138 inhibitor-attenuated inflammatory cytokines release of FLS cells. CONCLUSION: Here, we reveal miR-138 regulates RA-related inflammatory cytokines in rheumatoid arthritis through HDAC4/PGRN or HDAC4/NF-κB. Our findings uncover a new molecular mechanism implicated in rheumatoid arthritis, which may accelerate development of therapeutical strategy by targeting this mechanism. | |
31689449 | Intravital multiphoton microscopy as a novel tool in the field of immunopharmacology. | 2020 Feb | Intravital microscopy with multiphoton excitation is a recently developed optical imaging technique for deep tissue imaging without fixation or sectioning, which permits examination of fundamental concepts regarding the dynamic nature of cells under physiological and pathological conditions in living animals. This novel technique also offers exciting opportunities for pharmacological research by providing new platforms for the study of cellular dynamics in response to drugs in vivo. Moreover, fluorescent chemical probes for functional or molecular analysis in single cells in vivo play important roles in pharmacology. For example, we have recently revealed the pharmacodynamic actions of different biological agents for the treatment of rheumatoid arthritis (RA) in vivo by directly visualizing drug-induced cellular behaviors and functions of osteoclasts on bone surfaces. This review focuses on the principles and advantages of intravital imaging for the dissection of pharmacological mechanisms, and discusses how such imaging can contribute to the drug development process, introducing recent trials that evaluated the in vivo pharmacological effects of various agents. | |
30969989 | The comparative responsiveness of Hospital Universitario Princesa Index and other composit | 2019 | OBJECTIVE: To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. METHODS: Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Δ) of HUPI with Δ in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (ΔGDA-Phy). RESULTS: ΔHUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using ΔGDA-Phy as gold standard. CONCLUSION: HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR's. | |
31240388 | Cost per response for abatacept versus adalimumab in patients with seropositive, erosive e | 2019 Sep | BACKGROUND: Effective treatment of rheumatoid arthritis (RA) with biologic DMARDs poses a significant economic burden. The AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE RA subjects with background methotrexate) trial was a head-to-head, randomized study comparing abatacept with adalimumab. A post hoc analysis showed improved efficacy for abatacept in patients with versus without seropositive, erosive early RA. OBJECTIVE: The aim of the current study was to evaluate the cost per response (ACR20/50/70/90 and HAQ-DI) and patient in remission (DAS28-CRP, CDAI, and SDAI) for abatacept relative to adalimumab, in patients with seropositive, erosive early RA in the US, Germany, Spain, and Canada. METHODS: A previously published model was used to compare abatacept and adalimumab in a cohort of 1000 patients over 2 years. Clinical inputs were updated based on two subpopulations from the AMPLE trial. Cohort 1 included patients with early RA (disease duration ≤ 6 months), RF and/or ACPA seropositivity, and > 1 radiographic erosion. Cohort 2 included patients with RA in whom at least one of these criteria was absent. RESULTS: For cohort 1, all incremental costs per additional health gain (patient response or patient in remission) favoured abatacept in all countries, except for DAS28-CRP remission in Canada. Cost savings versus adalimumab were greater when more stringent response criteria were applied and also in cohort 1 patient (versus cohort 2 patients). CONCLUSION: The cost per responder and patient in remission favoured abatacept in patients with seropositive, erosive early RA across all the countries. In this patient population, the use of abatacept instead of adalimumab can lead to lower costs in the US, Germany, Spain, and Canada. | |
31061059 | Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate tr | 2019 May 5 | OBJECTIVES: To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure. DESIGN: Multicentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN). SETTING: Secondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland. PARTICIPANTS: Patients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3-6 months, at 12 months and annually thereafter. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis. RESULTS: Of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit. CONCLUSIONS: MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD. | |
31146113 | Proteomic analysis of biomarkers predicting the response to triple therapy in patients wit | 2019 Aug | OBJECTIVE: Patients with rheumatoid arthritis (RA) usually receive triple therapy with methotrexate (MTX), leflunomide (LEF) and infliximab (IFX), but nearly one-third of them do not respond to triple therapy. This study aimed to identify biomarkers for predicting the efficacy of triple therapy to optimize personalized treatment of RA. METHODS: All 20 enrolled patients met 2010 ACR/EULAR criteria for RA and were classified into good, moderate and non-responders (GR, MR, NR) for triple therapy. The Responders (R) were defined as the sum of GR and MR. Protein profiles of 4 responders and 4 non-responders were investigated via isobaric tags for relative and absolute quantification (iTRAQ), and differentially expressed proteins (DEPs) with high-confidence peptides were validated in 15 responders and 5 non-responders by parallel response monitoring (PRM). RESULTS: iTRAQ identified 51 DEPs between responders and non-responders (p < 0.05, fold change >±1.2). The top five up-regulated DEPs were B7Z7M2, A0A087WZR4, Q53FL1, P08254 and G3V2V8, while the top five down-regulated proteins were Q6MZX9, B3KP77, P0DJI9, P0DJI8 and P02787. Targeted mass spectrometry by PRM identified 10 candidate biomarkers, and 3 DEPs including fibrinogen beta chain, epididymal secretory protein Li 282 and testicular tissue protein Li 70 were confirmed as predictive biomarkers. CONCLUSION: This study demonstrated the feasibility of exploring biomarkers by applying iTRAQ and PRM mass spectrometry techniques, and a panel of biomarkers were identified to predict clinical response of IFX + MTX + LEF treatment in active RA patients. | |
31730497 | Predictors of good response to conventional synthetic DMARDs in early seronegative rheumat | 2019 Nov 15 | BACKGROUND AND OBJECTIVE: Early seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis. PATIENTS AND METHODS: Patients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes. RESULTS: One hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07-5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year. CONCLUSION: Our results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03666091. Registered September 11, 2018. | |
31415615 | Patterns of health care utilization of gout patients in Hawai'i-high rates of emergency de | 2019 | Recent and comprehensive research of gout in the Pacific region and Hawai'i is significantly lacking. This study was conducted to improve the understanding of the healthcare utilization of gout patients within a single health care system in Hawai'i. The objective was to examine gout inpatient, outpatient and emergency department care within a single health care system in Hawai'i. This study was a retrospective chart review of patients, ≥ 18 years admitted to three Hawai'i Pacific Health facilities for a primary diagnosis of gout or rheumatoid arthritis (RA) from 2011 to 2017. Population data for the State of Hawai'i was used to calculate visit rates per 1,000 Hawai'i adults. Trend analysis was performed to compare changes over time. We studied gout health care utilization concurrently with RA to provide an internal comparison group for the healthcare utilization patterns of interest. Gout patients were primarily managed in the outpatient setting with high rates of emergency department visits. In contrast, RA patients were primarily managed in the outpatient setting, with low rates of emergency department visits. Both gout and RA patients had low rates of inpatient admissions. The cost of gout emergency department visits was approximately 3.4 times higher than gout outpatient visits. The rates for gout emergency department visits, outpatient visits, inpatients visits, and RA outpatient visits in 2017 were trending downward and significantly changed from 2011 (p <0.05). The rates for RA emergency department visits and inpatient visits were not significantly changed from 2011-2017. Gout care in Hawai'i remains suboptimal with higher rates of emergency department visits, as compared to RA. Because emergency department visits are associated with higher cost, efforts should be made to reduce these emergency department visits to improve the quality of care. | |
31240863 | Potential benefits of biologics on stroke and mortality in patients with rheumatoid arthri | 2019 Aug | AIM: To examine the changes in the risks of death and cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients treated with conventional synthetic or biologic disease-modifying antirheumatic drugs (csDMARD or bDMARD) during 1997-2013. METHODS: Two cohorts of RA patients and their matched controls were identified from the National Health Insurance Research database. There were 1569 patients in the csDMARD cohort who received cyclosporine ≥50 mg/d with concomitant usage of ≥2 csDMARDs during 1997-2003. There were 1530 patients in the bDMARD cohort if patients had ≥1 claim for bDMARD during 2003-2011. Adjusted hazard ratios (aHRs) for the risk of death, myocardial infarction, and stroke, were assessed using the Kaplan-Meier survival curves and the Cox proportional hazards models. RESULTS: Compared with matched cohorts, the incidence of death was higher with csDMARD with a more than 6-fold increase (csDMARD vs controls: 33% vs 5%); while it only increased with a much smaller magnitude with bDMARD (bDMARD vs controls: 15% vs 11%). In addition, an increase in the reduction of incidence rate of stroke with bDMARD (bDMARD vs controls: 2% vs 5%) than that with csDMARD (csDMARD vs controls: 3% vs 4%) was found. Results from multivariate analysis showed that RA patients receiving bDMARD had a significantly lower increase in the risk of deaths (aHR 1.05; 95% CI 0.84-1.33) compared with those receiving csDMARD (aHR 8.75; 95% CI 7.43-10.31). In addition, bDMARD was associated with a higher reduction in the risk of stroke compared with csDMARD (bDMARD: aHR 0.37; 95% CI 0.22-0.62; csDMARD: aHR 0.73; 95% CI 0.51-1.05). CONCLUSION: Biologics used in RA patients have been shown to have a beneficial impact on improving clinical outcomes, including decreased risks of death and stroke. The economic burden from costs of biologics may be alleviated by improving outcomes. | |
30168277 | Carotid ultrasound findings in rheumatoid arthritis and control subjects: A case-control s | 2019 Jan | Rheumatoid arthritis (RA) is a chronic, inflammatory disease closely linked with atherosclerosis. Recommended cardiovascular disease (CVD) integral evaluation includes screening for asymptomatic atherosclerosis plaques with carotid ultrasound (US). The aim of this study is to evaluate the carotid US characteristics, including carotid intima media thickness (cIMT) and carotid plaque (CP), and compare RA-patients and controls in a Mexican-mestizo population. METHOD: Prospective cross-sectional, observational study comparing RA-patients and matched controls without RA. Medical history and physical exam was performed in all subjects by a rheumatologist and two clinical blinded radiologists did the carotid US. Increased cIMT was defined as ≥0.9 mm. CP was defined as a focal narrowing ≥0.5 mm of the surrounding lumen or a cIMT ≥1.2 mm. Multivariable analysis was done comparing RA-patients and control subjects characteristics with carotid US. RESULT: In the final analysis 209 patients were included, 103 patients with RA and 106 controls. Bilateral CP was found more than twice in RA than controls (15.5% vs 6.6%). Unilateral CP was more common in either side evaluated, being heterogeneous plaques the most common in RA-patients. The prevalence of increased cIMT was found higher in RA-patients either in both sides (right 37.9% vs 15.1%, P = 0.00; left 43.7% vs 19.8%, P = 0.00) were statistically significant. CONCLUSION: It was confirmed that RA-patients have greater subclinical atherosclerosis represented in the carotid US measuring cIMT and CP as surrogates. RA-patients with subclinical atherosclerotic disease have more heterogeneous plaques characteristics. | |
31494739 | The relation between upper extremity joint involvement and grip force in early rheumatoid | 2019 Dec | To investigate the relation between joint involvement in the upper extremities and grip force in patients with early rheumatoid arthritis (RA). An inception cohort of 225 patients with early RA was followed according to a structured protocol. The same rheumatologist assessed all patients for swollen joints and joint tenderness. Grip force was measured (Grippit; AB Detektor, Gothenburg, Sweden) at the same visit. Average grip force values for the dominant hand were expressed as % of expected, based on age- and sex-specific reference values from the literature. Associations between grip force and current synovitis or tenderness of individual joints, and other disease parameters measured at the same visit, were examined. Patients with current synovitis of the wrist joint or ≥ 1 metacarpophalangeal (MCP) joint of the dominant hand had a significantly lower grip force at inclusion, at 1 year and at 5 years. Proximal interphalangeal joint tenderness and MCP joint tenderness were consistently associated with reduced grip force. In multivariate analysis, extensive MCP joint synovitis was associated with lower grip force at inclusion (β - 2.8% per joint; 95% CI - 5.3 to - 0.4), and also at the 1-year follow-up. Patient reported pain scores and erythrocyte sedimentation rates had independent negative associations with grip force at all time points. In patients with early RA, extensive synovitis of the MCP joints was associated with reduced grip force, independently of other upper extremity joint involvement. Pain and inflammation have effects on hand function beyond those mediated by local synovitis. | |
31862264 | Diagnostic performance of 14-3-3η and anti-carbamylated protein antibodies in Rheumatoid | 2020 Mar | OBJECTIVES: As we already know, Rheumatoid arthritis (RA) cannot be excluded when the rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibody (anti-CCP) is negative. Here, we determined the application value of 14-3-3η protein, anti-carbamylated proteins antibodies (anti-CarP), as well as their potential role to diagnose RA together with RF or anti-CCP. METHOD: Serum levels of anti-CCP, RF, 14-3-3η and anti-CarP antibodies were detected in 291 RA patients, 223 patients with autoimmune diseases except RA, and 156 healthy subjects recruited from Han population of Northern China. We examined the differences in the levels of these indicators among groups and compared the correlations between any two of the indicators. At the same time, a total of 12 testing strategies were established for comparison to maximize the diagnostic value. RESULT: The levels of RF, anti-CCP, anti-CarP and 14-3-3η were significantly higher in RA patients (12.5;[9.36-15.7], 30.7;[25.7-35.6], 1.90;[1.70-2.01], 15.8;[10.8-20.8], respectively) compared with either interference-control group (1.24;[1.07-1.41], 0.64;[0.42-0.86], 0.51;[0.46-0.57], 0.33;[0.23-0.44], respectively) (p < 0.0001) or healthy-control group (1.03;[0.99-1.08], 0.49;[0.38-0.59], 0.28;[0.21-0.35], 0.55;[0.27-0.85], respectively) (p < 0.0001). Among all 12 detection strategies, the YI and κ value of a novel strategy that either double-positive of any 2 markers or single-positive of anti-CCP can be diagnosed as RA had the highest diagnostic value. CONCLUSION: The results of our study demonstrated that in Han population of Northern China, anti-CarP antibodies and 14-3-3η protein can be treated as valuable indicators of RA, especially when combined with RF and anti-CCP, the detection value is maximized. | |
31433746 | Clinical diagnostic significance of 14-3-3η protein, high-mobility group box-1, anti-cycl | 2020 Jan | Introduction: Circulating markers of rheumatoid arthritis (RA) include the 14-3-3η protein, high-mobility group box-1 (HMGB1), anti-cyclic citrullinated peptide (anti-CCP) antibodies, anti-mutated citrullinated vimentin (anti-MCV) antibodies and rheumatoid factor (RF). We set out to determine which two markers in combination provided best discriminatory power for this disease.Methods: We recruited 108 RA patients, 102 non-RA patients (SLE, AS, Sjogren's syndrome, MCTD) and 90 healthy controls. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and the Youden index of each analyte were calculated and binary logistic regression analysis and receiver operating characteristic (ROC) curve were performed to evaluate their diagnostic value for RA alone and in paired combination.Results: As expected, all markers were elevated in RA patients (P < 0.05). Binary logistic regression analysis showed that 14-3-3η had the highest odds ratio (95% CI) at 2.4 (1.9-2.8). Anti-CCP and anti-MCV had the highest areas under the curves [AUC (95% CI)] at 0.85 (0.78-0.90) and 0.85 (0.78-0.91) respectively (both P < 0.001). In serial detection (one marker followed by another), no combination had a Youden index >0.6. In parallel analysis (both considered together) several combinations had a Youden index >0.7, of which the highest (0.78) was anti-CCP with anti-MCV, with a sensitivity of 93.3% and specificity of 84.7%.Conclusions: Despite individual increases in serum 14-3-3η, HMGB1, anti-CCP, anti-MCV and RF, the combination of anti-CCP and anti-MCV might be of great help for diagnostic in RA, and so should be considered as routine tests for this disease. | |
30659109 | The Autoimmune Susceptibility Gene C5orf30 Regulates Macrophage-Mediated Resolution of Inf | 2019 Feb 15 | Genetic variants in C5orf30 have been associated with development of the autoimmune conditions primary biliary cirrhosis and rheumatoid arthritis. In rheumatoid arthritis, C5orf30 expression is cell-specific, with highest expression found in macrophages and synovial fibroblasts. C5orf30 is highly expressed in inflamed joints and is a negative regulator of tissue damage in a mouse model of inflammatory arthritis. Transcriptomic analysis from ultrasound-guided synovial biopsy of inflamed joints in a well characterized clinical cohort of newly diagnosed, disease-modifying antirheumatic drugs-naive rheumatoid arthritis patients was used to determine the clinical association of C5orf30 expression with disease activity. A combined molecular and computational biology approach was used to elucidate C5orf30 function in macrophages both in vitro and in vivo. Synovial expression of C5orf30 is inversely correlated with both clinical measures of rheumatoid arthritis disease activity and with synovial TNF mRNA expression. C5orf30 plays a role in regulating macrophage phenotype and is differentially turned over in inflammatory and anti-inflammatory macrophages. Inhibition of C5orf30 reduces wound healing/repair-associated functions of macrophages, reduces signaling required for resolution of inflammation, and decreases secretion of anti-inflammatory mediators. In an animal model of wound healing (zebrafish), C5orf30 inhibition increases the recruitment of macrophages to the wound site. Finally, we demonstrate that C5orf30 skews macrophage immunometabolism, demonstrating a mechanism for C5orf30-mediated immune regulation. |