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32600905 Radiological and clinical comparisons of the patients with rheumatoid arthritis operated w 2021 May BACKGROUND: It is extremely difficult to treat spine disorders with stabilization in patients with rheumatoid arthritis. Because revision rates are significantly higher in rigid stabilization. To date, there is no data about patients with rheumatoid arthritis treated with dynamic stabilization. Our aim was to compare the radiological and clinical results of patients with rheumatoid arthritis who underwent lumbar rigid stabilization or dynamic stabilization with Polyetheretherketone rod (PEEK). METHODS: Patients with degenerative lumbar spine disease with rheumatoid arthritis who underwent dynamic stabilization between 2013 and 2015 and rigid stabilization between 2010 and 2012 were evaluated radiologically for adjacent segment disease, proximal junctional kyphosis, system problem (nonunion, screw loosening, instrumentation failure, pull out). It was also compared according to both the revision rates and the Visual Analog Scale and Oswestry Disability Index scores at the 12th month and 24th month. RESULTS: The difference of decrease in Visual Analog Scale and Oswestry Disability Index scores from preoperative to 12th month between patients who underwent dynamic stabilization and rigid stabilization was statistically insignificant. However, there was a significant difference of increase in Visual Analog Scale and Oswestry Disability Index scores between the 12th month and 24th month of patients who underwent rigid stabilization, compared with patients with dynamic stabilization. In patients with dynamic stabilization, the problems of instrumentation were seen less frequently. Revision rates were high in patients with rigid stabilization when compared the patients with dynamic stabilization. CONCLUSION: Radiological and clinical outcomes in patients with rheumatoid arthritis operated with dynamic stabilization are more significant when compared to rigid stabilization. These patients have lower pain and disability scores in their follow up periods. Revision rates are lower in patients with dynamic stabilization.
34670873 Analysis of gut microbiota and metabolites in patients with rheumatoid arthritis and ident 2021 Oct 20 Rheumatoid arthritis (RA) is an autoimmune disease described by joint destruction, synovitis and pannus formation. The gut microbiota acts as an environmental factor that plays an important role in RA, but little research regarding the etiopathogenic mechanisms of the microbiome in RA has been carried out. We used an integrated approach of 16S rRNA gene sequencing and ultrahigh-performance liquid chromatography-mass spectrometry-based metabolomics to analyze the structure and diversity of the intestinal flora and metabolites of the gut microbiota in RA patients compared with healthy subjects. In this study, α-diversity analysis of the gut microbiota showed that there was no significant difference between the healthy control (HC) and RA groups. However, β-diversity analysis showed that there was a significant difference between the two groups. Further analysis of alteration of the gut microbiota revealed that at the phylum level, the relative abundance of p_Bacteroidetes was significantly decreased in the RA group, while that of Verrucomicrobia and Proteobacteria was significantly increased in the RA group. At the genus level, Bacteroides, Faecalibacterium and some probiotics were decreased in the RA group, while 97 genera, including Lactobacillus, Streptococcus and Akkermansia, were increased in the RA group. Seventy-four differentially abundant metabolites were identified between the HC and RA groups, and we identified two potential biomarkers (9,12-octadecadiynoic acid and 10Z-nonadecenoic acid) in RA.
34473908 Extra-articular involvement of rheumatoid arthritis in three seropositive patients in the 2021 Dec INTRODUCTION: Extra-articular involvement (EAI) in rheumatoid arthritis (RA) is rare, severe and usually presents after years of joint involvement. Onset of RA as lung involvement has been published. We describe a series of three patients with strongly positive anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) positive in the absence of joint symptoms, but with significant EAI. METHODS: This is a descriptive case series of three patients evaluated in an academic medical center rheumatology clinic. RESULTS: A 50-year-old female presented with severe recurrent scleritis in the background of strongly positive ACPA, but no joint involvement. Her ocular disease responded well to rituximab. Four years later, she developed peripheral inflammatory arthritis consistent with RA. A 74-year-old male presented after developing recurrent steroid-dependent serositis (pleuro-pericarditis) and interstitial lung disease (ILD). Serology was notable for strongly positive ACPA, but no joint involvement. Serositis responded well to adalimumab. Two years after initial symptoms, he developed peripheral joint involvement after holding adalimumab. A 56-year-old female presented with an isolated, biopsy-proven subcutaneous rheumatoid nodule. Subsequently, she developed pancytopenia and fatigue. She tested strongly positive for ACPA and RF. Bone marrow biopsy was negative for malignancy and she had no evidence of infection. She responded to steroids and hydroxychloroquine and had not developed joint involvement after 2 years of follow-up. CONCLUSION: EAI as an onset of RA is a complex and not easily recognized entity if typical joints involvement is not yet present. Early diagnosis may help guide specific therapy and prevent sequelae and co-morbidities.
34192633 Prevalence of sarcopenia and clinical implications in patients with newly diagnosed rheuma 2021 Oct OBJECTIVE: The aim of this study was to determine the frequency of sarcopenia at the time of diagnosis in patients with rheumatoid arthritis (RA), assessing disease activity and factors that may be associated with sarcopenia and observe effects of treatment on sarcopenia. METHOD: A prospective study was conducted with patients who have newly diagnosed RA. Patients were evaluated twice, at the time of diagnosis and 3 mo after the initiation of treatment. Demographic data, anthropometric measurements, disease activity scores, and sarcopenia status were recorded. Sarcopenia was evaluated with grip strength and bioelectric impedance. The results were compared with healthy volunteers. RESULTS: The age at onset of RA was 50.6 ± 14.6 y. Handgrip strength (P < 0.001), skeletal muscle mass (P = 0.009), and skeletal muscle mass index (P = 0.032) were reduced in patients with RA but not in the control group. The frequency of sarcopenia in RA at onset of diagnosis was 31.5%. There was a significant decrease in the rate of sarcopenia after 3 mo of treatment (31.5 versus 8.7%; P = 0.046). CONCLUSION: Sarcopenia was found in approximately one-third of the patients with newly diagnosed RA in our study. With treatment, sarcopenia improved significantly. Patients with RA should be evaluated in terms of sarcopenia in addition to evaluating joint and extraarticular findings at the time of diagnosis. Early detection and treatment planning may improve quality of life.
34369379 NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like syno 2021 Jun 1 Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by abnormal synovial hyperplasia and the release of inflammatory cytokines. NLRP12 is a member of the family nod-like receptor (NLR) families that are activators of inflammation. However, the role of NLRP12 in fibroblast-like synoviocytes (FLSs) is still unclear. In the present study, we have investigated the role of NLRP12 in fibroblast-like synoviocytes (FLSs). The results demonstrated that NLRP12 overexpression inhibited proliferation and promoted cell apoptosis in RA-FLSs. Moreover, NLRP12 overexpression repressed inflammation by downregulation of IL-1β, TNF-α, IL-6, IFN-γ and MCP-1 production and upregulation of IL-10 levels with knockdown of NLRP12 expression showing opposite effects. In addition, NLRP12 overexpression suppressed phosphorylation of JNK, ERK, p38 and NF-κB in RA-FLSs, whereas NLRP12 knockdown promoted phosphorylation of these proteins. In conclusion, these findings demonstrate that NLRP12 inhibits proliferation and inflammation of RA-FLSs via the regulation of the NF-κB and MAPK signaling pathways, suggesting that NLRP12 might be a potential target for RA treatment.
33032873 Ultrasonography-detected synovitis of hand is associated with the presence of synovitis in 2021 Sep BACKGROUND: In rheumatoid arthritis, forefoot disease activity can lead to joint damage, pain, and disability during weight-bearing activities; therefore, the evaluation and control of forefoot disease activity is important. We aimed to investigate an association between the prevalence of abnormalities in the forefoot based on ultrasonography (US) and the clinical and US findings related to arthritis and identify factors related to the presence of synovitis in the forefoot of RA patients. METHODS: In total, 810 metatarsophalangeal joints of 81 rheumatoid arthritis patients were examined using US. Patients were assigned to either a forefoot synovitis group (n = 22), with foot synovitis detected using US, or a non-forefoot synovitis group (n = 59). We assessed associations between clinical parameters and US finding of the hand and US finding of the metatarsophalangeal joints. RESULTS: The following were significantly higher in forefoot synovitis group than in non-forefoot synovitis group: swollen joint count [P < 0.001]; Disease Activity Score 28 based on C-reactive protein [P < 0.05]; clinical disease activity index [P < 0.001]; and total Power Doppler score of the hand [P < 0.001]. Receiver-operating characteristic analysis for total Power Doppler scores of the hand to suggest the presence of synovitis in the metatarsophalangeal joints showed that a total Power Doppler score of the hand of ≥5 was associated with synovitis in the metatarsophalangeal joints, with a sensitivity of 68% and a specificity of 85% (odds ratio = 11.9). CONCLUSION: Total Power Doppler scores of the hand had a good valuable score for suggesting the presence of synovitis in metatarsophalangeal joints of rheumatoid arthritis patients.
33538619 Consideration of differences in drug usage between young-onset and elderly-onset rheumatoi 2021 Nov OBJECTIVES: Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. METHODS: Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). RESULTS: There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. CONCLUSION: Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.
32986234 Performance of the RABBIT infection risk score in an Argentinian rheumatoid arthritis coho 2021 Feb Patients with rheumatic autoimmune diseases have a higher risk of infections compared with age-and sex-matched controls. In Latin America, there are no validated tools to assess the risk of serious infection. The objectives were to estimate the incidence of serious infections in a cohort of rheumatoid arthritis (RA) patients followed for 12 months and to validate the RABBIT risk score for serious infections. Patients with RA were included and followed for 12 months. Baseline sociodemographic data, comorbidities, RA characteristics, and vaccination status were recorded. The baseline RABBIT risk score was calculated. Serious infections were documented, describing site and time since enrollment. Six hundred five patients were included (13 centers). The incidence of serious infection was 5% (95% CI 3-7). The most frequent sites were respiratory and urinary (90%). Performance of RABBIT risk score: patients with no infection during follow-up had a median score of 1.2 (IQR 0.8-2.1) and patients with infection 5.1 (IQR 2.15-12.6) p 0.00001. ROC curve analysis: AUC 0.86 (95% CI 0.8-0.94), best cut-off 2.85 (sensibility 75%, specificity 85%). The incidence of serious infections was 5% during the follow-up. The RABBIT score performed excellently in our patients. Key Points • The RABBIT risk score for serious infections showed an excellent performance in a population different (Latin America) from the original one included in the German registry. • This may assist rheumatologists in selecting drugs for patients according to the individual risk of infection, in a fast and simple way.
34499588 Fascin1 mediated release of pro-inflammatory cytokines and invasion/migration in rheumatoi 2021 Nov Rheumatoid arthritis (RA) is a chronic, multi-factorial disease characterized by Synovial hyperplasia, chronic inflammation, and autoimmune reaction. Fascin1 overexpression has been implicated in cancer, immune, and inflammatory diseases. However, the relationship between Fascin1 and rheumatoid arthritis (RA) has not yet been determined. We investigated whether Fascin1 could modulate pro-inflammatory cytokine secretion and the proliferation, apoptosis, and invasion/migration of fibroblast-like synoviocytes (RA-FLSs). Fascin 1 was suppressed with a short interfering (si)RNA approach. Functional analysis contained MTT assay, flow cytometry,Transwellâ„¢ assays, wound healing, Quantitative polymerase chain reaction and western blotting were used to detect cell proliferation,apoptosis ratio, invasion/ migration, the mRNA and protein expression of the realted markers, respectively. Overexpression of fascin1 was observed in RA-FLSs group compared with control group. Fascin1 expression positively correlated with changes in the expression of RA disease activity markers (RF, CRP, and DAB28, respectively). We also observed a significant positive correlation between Fascin1 and STAT3 mRNA levels in RA- FLSs.Fascin1 silencing attenuated the expression of pro-inflammatory cytokines; reduced FLS proliferation in vitro; and increased apoptosis ratio and bax, cleaved PARP, and caspase-3 expression. si- Fascin1 transfection delayed RA-FLS invasion/migration and reversed the epithelial- mesenchymal transition. These data suggest that Fascin1 exerts positive effects on the proliferation, cell cycle, and invasion/migration of RA-FLSs by activating signal transducer and activator of transcription 3 signaling.After all, Fascin1 contributed to RA development.
33803502 Nanomaterials for the Diagnosis and Treatment of Inflammatory Arthritis. 2021 Mar 18 Nanomaterials have received increasing attention due to their unique chemical and physical properties for the treatment of rheumatoid arthritis (RA), the most common complex multifactorial joint-associated autoimmune inflammatory disorder. RA is characterized by an inflammation of the synovium with increased production of proinflammatory cytokines (IL-1, IL-6, IL-8, and IL-10) and by the destruction of the articular cartilage and bone, and it is associated with the development of cardiovascular disorders such as heart attack and stroke. While a number of imaging tools allow for the monitoring and diagnosis of inflammatory arthritis, and despite ongoing work to enhance their sensitivity and precision, the proper assessment of RA remains difficult particularly in the early stages of the disease. Our goal here is to describe the benefits of applying various nanomaterials as next-generation RA imaging and detection tools using contrast agents and nanosensors and as improved drug delivery systems for the effective treatment of the disease.
33993117 Systematic Review and Metaanalysis of the Reproducibility of Patient Self-reported Joint C 2021 Dec OBJECTIVE: To assess the reproducibility of patient-reported tender (TJCs) and swollen joint counts (SJCs) of patients with rheumatoid arthritis (RA) compared to trained clinicians. METHODS: We conducted a systematic literature review and metaanalysis of studies comparing patient-reported TJCs and/or SJCs to clinician counts in patients with RA. We calculated pooled summary estimates for correlation. Agreement was compared using a Bland-Altman approach. RESULTS: Fourteen studies were included in the metaanalysis. There were strong correlations between clinician and patient TJCs (0.78, 95% CI 0.76-0.80), and clinician and patient SJCs (0.59, 95% CI 0.54-0.63). TJCs had good reliability, ranging from 0.51 to 0.85. SJCs had moderate reliability, ranging from 0.28 to 0.77. Agreement for TJCs reduced for higher TJC values, suggesting a positive bias for self-reported TJCs, which was not observed for SJCs. CONCLUSION: Our metaanalysis has identified a strong correlation between patient- and clinician-reported TJCs, and a moderate correlation for SJCs. Patient-reported joint counts may be suitable for use in annual review for patients in remission and in monitoring treatment response for patients with RA. However, they are likely not appropriate for decisions on commencement of biologics. Further research is needed to identify patient groups in which patient-reported joint counts are unsuitable.
33682730 Decreased Risk of Parkinson's Disease After Rheumatoid Arthritis Diagnosis: A Nested Case- 2021 BACKGROUND: Rheumatoid arthritis (RA) and the genetic risk landscape of autoimmune disorders and Parkinson's disease (PD) overlap. Additionally, anti-inflammatory medications used to treat RA might influence PD risk. OBJECTIVE: To use a population-based approach to determine if there is an association between pre-occurring rheumatoid arthritis (RA) and later-life risk of PD. METHODS: The study population was 3.6 million residents of Sweden, who were alive during part or all of the follow-up period; 1997-2016. We obtained diagnoses from the national patient registry and identified 30,032 PD patients, 8,256 of whom each was matched to ten controls based on birth year, sex, birth location, and time of follow-up. We determined the risk reduction for PD in individuals previously diagnosed with RA. We also determined if the time (in relation to the index year) of the RA diagnosis influenced PD risk and repeated the analysis in a sex-stratified setting. RESULTS: Individuals with a previous diagnosis of RA had a decreased risk of later developing PD by 30-50% compared to individuals without an RA diagnosis. This relationship was strongest in our conservative analysis, where the first PD diagnosis occurred close to the earliest PD symptoms (odds ratio 0.47 (CI 95% 0.28-0.75, p = 0.0006); with the greatest risk reduction in females (odds ratio 0.40 (CI 95% 0,19-0.76, p = 0.002). DISCUSSION: Our findings provide evidence that individuals diagnosed with RA have a significantly lower risk of developing PD than the general population. Our data should be considered when developing or repurposing therapies aimed at modifying the course of PD.
34520733 The pharmacological assessment of resveratrol on preclinical models of rheumatoid arthriti 2021 Nov 5 Resveratrol/RES (3,5,4'-trihydroxy-trans-stilbene) is a natural compound found in many food items and red wine, which exhibits pleiotropic biological effects. Several preclinical studies evaluating the efficacy of RES in animal models of rheumatoid arthritis (RA) have been conducted, but the diversity of the experimental conditions and of their outcomes preclude definitive conclusions about RES's efficacy. We, therefore, performed a meta-analysis to assess its efficacy in mitigating experimental RA. We searched three databases until January 2021 and used the random-effects model for drawing inferences. Eighteen studies involving 544 animals were used in this study. Pooled analysis showed that experimental RA causes paw swelling (Hedge's g = 9.823, p = 0.000), increases polyarthritis score and arthritis index, and RES administration reduces paw volume (Hedge's g = -2.550, p = 0.000), polyarthritis score, and arthritis index besides amelioration in the histopathological score and cartilage loss. RA is accompanied by increased oxidative stress due to high malondialdehyde (MDA) level (p < 0.001) and low superoxide dismutase (SOD) activity (p = 0.002), and RES reduced MDA level (p < 0.001) and increased SOD activity (p < 0.001). Experimental RA exhibited an increase in pro-inflammatory cytokines viz. tumor necrosis factor (TNF)-α (p < 0.001), interleukin (IL)-6 (p = 0.002), and IL-1 (p < 0.001); however, insufficient quantitative data precluded us from assessing changes in the anti-inflammatory cytokine, IL-10. In experimental RA, RES decreased TNF-α (p < 0.001), IL-6 (p < 0.001) and IL-1 (p = 0.001) and increased IL-10. This meta-analysis suggests that RES can be a clinically effective therapy for RA, pending clinical trials.
33689842 Influence of prognosis factors on the prescription of targeted treatments in rheumatoid ar 2021 Jul OBJECTIVES: To explore current evidence on the management of poor prognostic factors in rheumatoid arthritis (RA) and to investigate whether this evidence is taken into account by clinicians when deciding on treatment in daily clinical practice. METHODS: We performed a systematic literature review (SLR) to analyse the effects of currently available biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) on the classically accepted poor prognostic factors of RA. All randomized controlled trials reporting subgroup analyses about effects on prognostic factors were identified and synthesized. In a second phase, a two-round Delphi survey was carried out to contrast the SLR results with the grade of agreement of a large group of rheumatologists about the effectiveness of each drug class on each prognostic factor. RESULTS: According to the Delphi results, the only prognostic factor that significantly influenced the selection of treatment was the presence of interstitial lung disease (ILD), being the preferred treatment in this scenario abatacept or rituximab. The rest of the poor prognostic factors (including high disease activity at baseline, disability as measured by the Health Assessment Questionnaire index, seropositivity, elevated acute-phase reactants, and evidence of erosions based on plain radiography or ultrasonography) did not seem to significantly influence rheumatologists when choosing a treatment. The results of the SLR results did not show solid evidence regarding the use of any specific therapy in the management of patients with specific poor factors, except in the case of RA-ILD, although the data in the literature in this regard are not free of bias. CONCLUSIONS: The only prognostic factor that seems to significantly influence the selection of treatment is the presence of RA-ILD.
33463632 SPECT imaging and highly efficient therapy of rheumatoid arthritis based on hyperbranched 2021 Mar 10 Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. Although significant progress has been made in clinical treatment, joint inflammation may continue or worsen, and may even progress to the end-stage that requires joint replacement. Traditional therapy using methotrexate (MTX) would cause serious off-target systemic toxicities. Therefore, it is crucial to effectively and specifically deliver MTX to targeted inflamed joints to decrease its adverse systemic toxicities and improve its therapeutic index. Herein, we develop multifunctional nanocarriers for diagnostic radioisotope (99mTc) labeling and therapeutic targeted drug (MTX) delivery by using PEGylated hyperbranched semiconducting polymer nanoparticles (HSP-PEG-NPs) as carriers. Upon intravenous administration, the nanoparticles can extravasate through the turbulent blood-joint barrier and access the inflamed joints. In vivo SPECT/CT imaging shows high accumulation in the inflamed joints of mice with RA after intravenous injection of HSP-PEG-NPs with 99mTc labeling (99mTc-HSP-PEG). In vivo therapeutic evaluations suggest that MTX@HSP-PEG-NPs significantly alleviate RA with a high therapeutic index and relatively low adverse systemic toxicities in comparison with free MTX at the same dose. Our study shows that HSP-PEG-NPs could serve as multifunctional vehicles to deliver radioisotopes for in vivo imaging, and MTX for RA treatment, highlighting the innovative development of the nanoparticle-based RA treatment strategy for clinical applications.
34737113 Development of an intelligent, stimuli-responsive transdermal system for efficient deliver 2021 Dec 15 The present study aimed to fabricate and evaluate the therapeutic efficacy of pH-responsive Ibuprofen (IB) nanoparticles (NPs) loaded transdermal hydrogel against rheumatoid arthritis (RA). The IB loaded Eudragit® L 100 (EL 100) nanoparticles were formulated through a modified nanoprecipitation technique and optimized using central composite design software. The optimized NPs were loaded into Carbopol® 934-based hydrogel by solvent evaporation method and were analyzed for physicochemical characteristics. The mean particle size of the prepared NPs was 48 nm with an entrapment efficiency of 90%. The transdermal hydrogel showed a pH-responsive sustained drug release and high penetration through the skin. Moreover, the prepared nanocarrier system exhibited therapeutic efficacy at inflamed joints' sites both in acute and chronic RA mice model. The therapeutic efficacy of the prepared formulation was confirmed through the results of various behavioral, biochemical, and cytokines-based assays. Similarly, the assessment of histopathological and radiological images, as well as the skin irritation studies further strengthens the potential use of the prepared formulation through the transdermal route. The current findings suggested that IB loaded pH-responsive NPs based transdermal hydrogel can be used as an efficient agent to manage RA.
34433333 MicroRNA-137-mediated inhibition of lysine-specific demethylase-1 prevents against rheumat 2021 Jan BACKGROUND: It has been increasingly reported that microRNAs (miRNAs) are related to rheumatoid arthritis (RA) pathogenesis. This present research was conducted to analyze the functions of miR-137 and the underlying molecular mechanism in RA progression. METHODS: Differentially expressed miRNAs in RA patients were analyzed using microarray-based analyses. Next, experiments involving miR-137 overexpression were performed to analyze the role of miR-137 in human fibroblast-like synoviocytes-RA (HFLS-RA) using cell counting kit-8 (CCK-8) assay, EdU staining, Transwell assay and flow cytometry, respectively. The function of miR-137 in inflammation was determined using ELISA. The binding relationship between miR-137 and LSD1 was confirmed by dual-luciferase reporter gene assay and ChIP test. Besides, a rat model with RA was established for in vivo experiments. RESULTS: miR-137 was downregulated in RA tissues and cells, which was negatively correlated with inflammatory factors. Upregulated miR-137 suppressed growth, migration and invasion of HFLS-RA, but promoted apoptosis. Lysine-specific demethylase-1 (LSD1) was a target of miR-137 and could be negatively regulated by miR-137. Moreover, LSD1 could activate REST through demethylation, while the REST/mTOR pathway induced levels of pro-inflammatory factors in RA. We observed the similar results in our in vivo study. CONCLUSION: This study suggested that miR-137 reduced LSD1 expression to inhibit the activation of REST/mTOR pathway, thus preventing against inflammation and ameliorating RA development. Our research may offer new insights into treatment of RA.
34948087 Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe 2021 Dec 10 Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.
33185166 Predictors of Cardiovascular Affection in Patients with Active Rheumatoid Arthritis: Secon 2021 OBJECTIVE: This is a secondary analysis of a randomized controlled trial that aimed to assess subclinical atherosclerosis in patients with rheumatoid arthritis (RA) by measuring carotid artery intima-media thickness (CIMT) and correlating it with disease activity and inflammatory markers (including levels of matrix metalloproteinase-3(MMP-3) and matrix metalloproteinase-9 (MMP-9)) and to detect the effectiveness of agents that inhibit matrix metalloproteinases (MMPs) as doxycycline in RA therapy. METHODS: One hundred and sixty RA patients were assigned in a randomized clinical trial (clinicaltrial. gov NCT03194204). Disease activity score 28(DAS28), laboratory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MMP-3, and MMP-9 were evaluated and mean CIMT was measured. Subjects were allocated randomly into one of two treatment arms, either methotrexate (MTX) alone or MTX with doxycycline 200mg per day orally. Follow up ESR, CRP, DAS28, MMP-3, and MMP-9 levels were re-evaluated after 3 months. RESULTS: There were positive significant correlations between CIMT and disease duration (r = 0.461, p = 0.001), age (r=0.459, p= 0.001), DAS28 score (r= 0.547, p = 0.001), ESR (r =0.413, p = 0.001), CRP (r = 0.281, p = 0.001), MMP-3 (r = 0.476, p = 0.001), and MMP-9 (r = 0.593, p =0.001). Patients treated with MTX and doxycycline showed lower levels of DAS28, ESR, CRP, MMP-3, and MMP-9 and this was statistically significant. CONCLUSION: CIMT seems to be the ultimate method to screen for subclinical atherosclerosis in RA patients. MMP-3 and 9 play a key role in both RA synovitis and cardiovascular changes, making them important therapeutic targets, especially with safe and cost-effective agents like doxycycline. This clinical trial was carried out in Assiut University Hospital (AUH), Assiut, Egypt (Clinical Trial Registration No. clinicaltrial.gov NCT03194204).
32605468 Interleukin-17 Gene Polymorphism (Rs2275913 G/A, Rs763780 C/T) in Rheumatoid arthritis：M 2021 Aug INTRODUCTION: The association between interleukin(IL)-17A and IL-17 F gene polymorphism with rheumatoid arthritis (RA) were inconsistent among previous studies. This meta-analysis aimed to determine the association between IL-17A and IL-17 F gene polymorphism with RA. METHODS: We searched Medline up to February 2020. Meta-analyses were performed for the comparisons of allele and multiple genetic models, including dominant, recessive, heterozygous, and homozygous models using fixed or random effects models. Odds ratios (OR) with 95% confidence intervals (95%CI) were utilized to assess the potential relationship. RESULTS: A total of 2315 confirmed cases and 2342 controls were included from eligible 10 case-controls studies. Meta analysis suggested that rs2275913 G allele increased the risk of RA in Caucasians (G vs A: OR = 1.14, 95% CI = 1.00-1.29, P = .044), but not in Mongolians (P > .05). Pooled analysis suggested that a significant associations between rs763780 C allele with RA susceptibility (C vs T: OR = 1.83, 95% CI = 1.13-2.97, P = .014). Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to RA risk in two races (P < .001). TSA plot revealed that the present study sufficient to draw a conclusion. CONCLUSIONS: This meta-analysis demonstrates IL-17A and IL-17 F genes play a significant role in RA, but its role in Mongolian populations needs further exploration.