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

ID PMID Title PublicationDate abstract
35089255 Uncontrolled blood pressure among hypertensive adults with rheumatoid arthritis in Saudi A 2022 Jan 28 Despite the availability and advancement of diagnostic and treatments with demonstrated benefits in minimizing cardiovascular morbidity and mortality, hypertension control rates remain suboptimal. Therefore, this research aimed to determine the prevalence of uncontrolled BP in rheumatoid arthritis (RA) patients and understand all potential risk factors for uncontrolled BP.We conducted a cross-sectional study on RA patients in 2 rheumatology clinics in 2 public hospitals in Riyadh. Patients' information such as demographics, comorbidities, drug use, and other clinical data were captured through a review of medical records and supplemented by patient interviews. Multivariate logistic regression was utilized for the analysis to identify the significant factors of uncontrolled BP (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg).In total, 834 subjects with RA and concomitant BP were involved in this cross-sectional study. The prevalence of uncontrolled BP was found to be 31.65% among all the study population. Multivariate analysis showed that males, subjects above 60 years of age, and smokers had a distinctly higher occurrence of uncontrolled BP. Among the patients with comorbid conditions, those with obesity, hyperlipidemia, diabetes, anemia, cancer, and reflex or gastroesophageal reflux disease also showed a significantly higher risk of uncontrolled BP (P < .05).The rate of uncontrolled BP was found to be alarmingly high in the study population. Age, gender, smoking, diabetes, obesity, hyperlipidemia, cancer, gastroesophageal reflux disease, and osteoporosis are independently linked with lack of BP control.
35538632 Culturally sensitive care of Misak Indigenous patients with rheumatoid arthritis in Colomb 2022 May INTRODUCTION: To describe and understand the attitudes, cultural knowledge, and therapeutic practices of the Misak people concerning rheumatoid arthritis (RA), inscribed in an emergent culturally sensitive healthcare model along with the indigenous community and health professionals, following a respectful and empathic relational contact approach to the inter-ethnic encounter. METHODS: A qualitative study that used ethnographic methods using observation techniques and in-depth interviews was carried out in the Misak community, Colombia, by a multidisciplinary team (rheumatology, physiotherapy, and anthropology). A thematic analysis based around the concept of explanatory models (EMs) was carried out. RESULTS: Researchers interviewed 20 patients with RA, 12 traditional healers, and 5 health professionals. The following themes were identified: (1) the traditional healers are allowed to practice only if the community recognizes their vocation; (2) two types of EM were observed: Misak community EM related to conception of RA and its treatment, shared by patients and the traditional healers; and biomedical EM. The interaction of the two types is still a healthcare challenge that requires articulating to achieve better clinical outcomes for patients. CONCLUSION: The EMs of RA care identified in the Misak community are focused on both the patients and the traditional healers. However, this predominant EM and the biomedical EM of RA care need to be brought closer together to contribute to the construction of a unifying model of a culturally sensitive care.
34014053 Physicians' Biological Drug Preference in Patients With Rheumatoid Arthritis and Spondyloa 2022 Mar 1 OBJECTIVE: Because of concerns about malignancy risks, using biological disease-modifying antirheumatic drugs (bDMARDs) in patients with a history of malignancy remains a challenging issue in rheumatology practice. This study aimed to investigate bDMARD preferences of physicians when treating of rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients with a history of malignancy. METHODS: The data for this cross-sectional study were gathered from the TReasure database using a date range of December 2017 and January 2020. Biological disease-modifying antirheumatic drug preferences were analyzed for 40 RA patients and 25 SpA patients with a history of malignancy. RESULTS: The most frequently prescribed bDMARD was rituximab, which was given to 28 RA patients (70%). For 25 patients (62.5%), the time between the diagnosis of malignancy and starting on a bDMARD regimen was less than 60 months, with a median interval of 43.5 months. Among SpA patients, the preferred bDMARDs were secukinumab and etanercept, which were each administered to 7 patients (28%). For 13 SpA patients (52%), the time between the diagnosis of malignancy and starting on bDMARDs was less than 60 months, with a median interval of 97 months. CONCLUSIONS: The observed bDMARD preferences may be related to the therapeutic effects of rituximab on lymphoproliferative malignancies, the protective effects of secukinumab on tumor progression, and the short half-life of etanercept. Biological disease-modifying antirheumatic drugs should be used in RA and SpA patients with malignancy in case of high inflammatory activity.
33428479 Association of methotrexate use and lymphoproliferative disorder in patients with rheumato 2022 Jan 5 OBJECTIVES: To investigate the risk factors and clinical characteristics of lymphoproliferative disorder (LPD) in Japanese patients with rheumatoid arthritis (RA). METHODS: We enrolled patients with RA aged ≥20 years who visited the participating hospitals between April 2011 and July 2011. We investigated the risk factors for LPD using a Cox proportional hazard model and described pathological features and vital prognosis of LPD in patients with RA. RESULTS: We enrolled 9815 patients with the following characteristics at baseline: female 79.4%, median age 63 years; median disease duration 7 years; median DAS28-CRP (3) 3.1; prevalence of MTX use 60.0%. Sixty-eight patients (0.69%) developed LPD in 3-year observation period. Multivariable analysis showed that age by decade (hazard ratio [95% confidence interval], 1.47 [1.18-1.85]) and MTX use at baseline (2.35 [1.25-4.42] for ≤8 mg/week, 4.39 [2.07-9.32] for >8 mg/week versus non-use) were significant risk factors of LPD. Of 55 patients with pathological diagnosis, diffuse large B cell lymphoma was the most frequent (54%). The 5-year mortality of LPD was 24%. The major cause of death was lymphoma (81%). CONCLUSION: This nationwide study revealed risk factors, clinical characteristics, and prognosis of LPD in the largest number of Japanese patients with RA.
34773548 Long Non-Coding RNA NEAT1 Knockdown Alleviates Rheumatoid Arthritis by Reducing IL-18 thro 2022 Feb Rheumatoid arthritis (RA) is chronic inflammatory autoimmune disease. The crucial role of long non-coding RNA (lncRNA) in the progression of RA has been highlighted. Hence, this study was designed to explore the specific downstream mechanism of lncRNA nuclear-enriched abundant transcript 1 (NEAT1) in RA. Initially, the expression of NEAT1, p-p65, p300, and IL-18 in clinical tissues and cells was determined. Then, interactions among p65, NEAT1, p300, CBP, and IL-18 were investigated by immunofluorescence staining, dual luciferase reporter gene assay, RT-qPCR assay ChIP assay, and RIP assay followed by the analysis of their effects on RA in vivo and in vitro after expression alteration. The expressions of NEAT1, p-p65, p300, and IL-18 were all upregulated in the synovial tissues from the mice and patients with RA. NEAT1 silencing reduced the infiltration of CD4(+) T cells and macrophages in synovial tissues, downregulated expression of blood inflammatory factors, relieved RA severity, and lowered incidence of RA in mice. Further, p-p65 could increase the expression of NEAT1 by binding to the NEAT1 promoter region, NEAT1 could co-locate and interact with p300, thus regulating the expression of IL-18 by regulating histone acetylation modification in IL-18 promoter region. NEAT1 aggravated RA via p300/CBP/IL-18 axis, representing a promising therapeutic target in RA.
34874123 Increased Risk of COVID-19 in Patients With Rheumatoid Arthritis: A General Population-Bas 2022 May OBJECTIVE: Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections owing to immunologic dysfunction and use of potent immunomodulatory medications; however, few data are available on their risk of COVID-19. We estimated the rate of COVID-19 among RA participants and compared it with that of the general population. METHODS: Using the Health Improvement Network, we identified RA patients before February 2020 and followed them to September 2020. We calculated the rate of COVID-19 among participants with RA and compared it with that of the general population using a Cox proportional hazards model, adjusting for potential confounders using overlap weighting of exposure score. We repeated the same analysis among participants with osteoarthritis, a nonautoimmune rheumatic disease, as a negative control exposure. RESULTS: We identified 225 cases of suspected and confirmed COVID-19 among 17,268 RA patients, and 14,234 cases among 1,616,600 participants in the general population (1.4 versus 0.9/1,000 person-months), with the adjusted hazard ratio (HR(adj) ) being 1.19 (95% confidence interval [95% CI] 1.04-1.36). Confirmed COVID-19 cases developed in 46 RA participants and in 2,249 in the general population (0.3 versus 0.1/1,000 person-months), with the HR(adj) being 1.42 (95% CI 1.01-1.95). No statistically significant difference was observed for suspected and confirmed (HR 1.00 [95% CI 0.93-1.07]) or confirmed (HR 1.08 [95% CI 0.92-1.27]) COVID-19 rates between participants with osteoarthritis and the general population. CONCLUSION: RA, but not osteoarthritis, was associated with an increased risk of COVID-19. Our findings provide timely evidence to support recommendations that booster vaccines and priority access to anti-SARS-CoV-2 monoclonal antibody treatments should be encouraged for RA patients.
35259677 Rituximab for prevention of strokes in cerebral rheumatoid vasculitis. 2022 Apr Rheumatoid arthritis (RA) is an autoimmune disorder which manifests as inflammation of the synovial joints alongside extra-articular involvement. Uncommonly, patients may develop vasculitis of small and medium-sized blood vessels, formally diagnosed as systemic rheumatoid vasculitis (SRV). In particularly rare cases, patients may develop a subtype of SRV known as cerebral rheumatoid vasculitis (CRV) which manifests in patients as stroke. To date, no formal recommendations or guidelines have been established for treatment and prevention of CRV-induced stroke besides experiential therapy with various immunomodulators. Here, we describe the utility of Rituximab in addition to steroids for prevention of stroke in our patient with evidence of multiple CRV-induced strokes with excellent recovery of post-stroke symptoms and remission of new onset cerebral vasculitis processes.
32486855 Long-term Outcomes of MCP Surface Replacement Arthroplasty in Patients With Rheumatoid Art 2022 Mar Background: Surface replacement arthroplasty (SRA) can be used in the treatment of rheumatoid arthritis (RA) affecting the metacarpophalangeal (MCP) joint. The authors of this study sought to investigate the outcomes of MCP SRA in patients with RA. Methods: Retrospective review of medical records and an institutional joint registry were used to gather data on 80 MCP SRAs performed in 27 patients with RA. Data collected included demographics, SRA revisions, reoperations, complications, pain, and MCP arc of motion. Results: The mean postoperative follow-up was 9.5 years (range, 2.1-20.5 years), with all SRAs achieving at least 2 years of follow-up. Thirteen digits (16%) underwent revision arthroplasty, and 29 (36%) required reoperation. The 5-, 10-, 15-, and 20-year rates of survival from implant revision were 95%, 85%, 80%, and 69%, respectively. The 5-, 10-, 15-, and 20-year rates of survival from overall reoperation were 80%, 65%, 55%, and 46%, respectively. Metacarpophalangeal joint arc of motion, grip strength, and pain levels significantly improved following surgery. Conclusions: Metacarpophalangeal SRA can offer benefit to patients with RA for improvement in function and pain. High overall reoperation rates remain concerning; however, most do not involve arthroplasty revision.
35119779 Implementing a Treat-to-Target Approach for Rheumatoid Arthritis During the COVID-19 Pande 2022 Apr OBJECTIVE: A treat-to-target (TTT) approach improves outcomes in rheumatoid arthritis (RA). In prior work, we found that a learning collaborative (LC) program improved implementation of TTT. We conducted a shorter virtual LC to assess the feasibility and effectiveness of this model for quality improvement and to assess TTT during virtual visits. METHODS: We tested a 6-month virtual LC in ambulatory care. The LC was conducted during the 2020-2021 COVID-19 pandemic when many patient visits were conducted virtually. All LC meetings used videoconferencing and a website to share data. The LC comprised a 6-hour kickoff session and 6 monthly webinars. The LC discussed TTT in RA, its rationale, and rapid cycle improvement as a method for implementing TTT. Practices provided de-identified patient visit data. Monthly webinars reinforced topics and demonstrated data on TTT adherence. This was measured as the percentage of TTT processes completed. We compared TTT adherence between in-person visits versus virtual visits. RESULTS: Eighteen sites participated in the LC, representing 45 rheumatology clinicians. Sites inputted data on 1,826 patient visits, 78% of which were conducted in-person and 22% of which were held in a virtual setting. Adherence with TTT improved from a mean of 51% at baseline to 84% at month 6 (P for trend < 0.001). Each aspect of TTT also improved. Adherence with TTT during virtual visits was lower (65%) than during in-person visits (79%) (P < 0.0001). CONCLUSION: Implementation of TTT for RA can be improved through a relatively low-cost virtual LC. This improvement in TTT implementation was observed despite the COVID-19 pandemic, but we did observe differences in TTT adherence between in-person visits and virtual visits.
35102535 Ultrasound-detected tenosynovitis as a risk factor for flares in rheumatoid arthritis pati 2022 Jun BACKGROUND: Our objective was to investigate the value of ultrasound (US) detected synovitis and tenosynovitis as risk factors for short term flare in rheumatoid arthritis (RA) patients in clinical remission. METHODS: Consecutive RA patients in clinical remission (DAS28 ERS < 2.6) for at least 3 months underwent Power Doppler ultrasound (PDUS) examination of 1st to 6th extensor compartments at the wrist, 2nd to 5th finger flexor, posterior tibial tendon, and peroneal tendons. To assess synovitis, carpal joints, 1st to 5th metacarpophalangeal (MCP) joints, and 2nd to 5th interphalangeal proximal (IPP) joints were bilaterally examined. Synovitis and tenosynovitis were defined according to OMERACT. Patients were followed for 1 year. Disease flare was defined as an increase in disease activity generating the need for a change in therapy by the attending rheumatologist. RESULTS: Ninety patients were included. After 1 year of follow-up, 26 patients (29%) experienced a flare. At baseline 39%, 23% and 8% had US-detected synovitis, tenosynovitis or both, respectively. In the 1-year period after the baseline US examination, US-detected tenosynovitis (RR: 4.9; 95% CI: 2.2-10.8) was associated with an increased risk of exacerbation. This association was not shown with US-detected synovitis (RR: 1.3; 95% CI: 0.76-2.2). In the multivariate analysis, only subclinical tenosynovitis (OR: 9.8; 95% CI: 2.5-39.1; p = 0.001) and baseline DAS28 (OR: 5.7; 95% CI: 1.1-31.6; p = 0.047) were significantly associated with an increased risk of having a flare. CONCLUSION: In our study, subclinical tenosynovitis was associated with disease flare in patients with RA in clinical remission. KEY POINTS: • Synovitis and tenosynovitis are risk factors for short term flare in RA patients in clinical remission. • Subclinical tenosynovitis, but not synovitis, was associated with disease flare in patients with unstable remission. • Ultrasound-detected tenosynovitis could be useful to predict relapses in RA patients in clinical remission.
35509008 Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid 2022 May 4 BACKGROUND: Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are chronic autoimmune diseases, but they are usually difficult to distinguish in the early stage of the diseases. The purpose of this study is to explore the differences of immune mechanism and diagnostic markers through bioinformatics analysis. METHODS: First, microarray datasets from patients with SpA, RA and normal controls were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between groups were identified in R software. Functional and pathway enrichment of DEGs were analyzed by David database. Then, we screened the hub genes using Cytoscape plugin, and constructed the protein-protein interaction (PPI) network and heatmap of hub genes. After that, CIBERSORT was used to evaluate the differences and connections of immune cells in SpA and RA, and screened out diagnostic markers. Correlation analysis was used to analyze the relationship between immune cells and diagnostic markers. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the effectiveness of immunodiagnostic markers. RESULTS: We obtained three datasets, from which we can see that the functional enrichment of DEGs is mainly in cell chemotaxis, lymphocyte activation, primary immunodeficiency and other immune responses. The difference of immune cells between SpA, RA and normal control was concentrated in B, T lymphocytes cells, macrophages and dendritic cells. C19orf12 + S1PR3 is most associated with these immune cells and S1PR3 can be used as a diagnostic marker of this kind of immune diseases. In addition, MZB1 + XIST is closely related to T cells, NK cells and dendritic cells, and is expected to be used as a marker to distinguish the two diseases. CONCLUSION: Although the clinical manifestations of SpA and RA are similar, the pathogenesis is different. The screening of immune cells and diagnostic markers provides a more accurate target for the treatment of this kind of diseases.
33859125 Are Cannabis, Cannabis-Derived Products, and Synthetic Cannabinoids a Therapeutic Tool for 2022 Mar 1 BACKGROUND: Symptom management in rheumatoid arthritis (RA) remains a complex challenge. Widespread use of cannabis-based medicines for a myriad of symptoms has fostered rheumatology patients' interest. However, their safety and efficacy in RA remain unclear. OBJECTIVE: The aim of this study was to perform a structured summary of the body of evidence in order to determine whether cannabis, cannabis-derived products, and synthetic cannabinoids are an effective treatment for rheumatoid arthritis. METHODS: An electronic search in Epistemonikos database was performed to identify systematic reviews and their primary studies that addressed our clinical question. The body of evidence was collected in a pivot table in Epistemonikos. Information and data from the primary studies were extracted from the identified reviews. Finally, extracted data were reanalyzed, and a summary of findings table was generated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Twenty-six systematic reviews were identified which included in total only 1 randomized trial assessing our clinical question. CONCLUSIONS: Cannabis, cannabis-derived products and synthetic cannabinoids may slightly reduce disease activity in patients with RA. Its use may result in little to no difference in pain reduction and may slightly increase nervous system adverse events. The evidence is very uncertain about the effect of cannabis, cannabis-derived products, and synthetic cannabinoids on serious adverse events risk.
35041143 Metabolomics of Synovial Fluid and Infrapatellar Fat Pad in Patients with Osteoarthritis o 2022 Jun Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases with complex and insufficiently understood pathogeneses. Our objective was to characterize the metabolic fingerprints of synovial fluid (SF) and its adjacent infrapatellar fat pad (IFP) obtained during the same surgical operation from OA and RA knees. Non-targeted metabolite profiling was performed for 5 non-inflammatory trauma controls, 10 primary OA (pOA) patients, and 10 seropositive RA patients with high-resolution mass spectrometry-based techniques, and metabolites were matched with known metabolite identities. Groupwise differences in metabolic features were analyzed with the univariate Welch's t-test and the multivariate linear discriminant analysis (LDA) and principal component analysis (PCA). Significant discrimination of metabolite profiles was discovered by LDA for both SF and IFP and by PCA for SF based on diagnosis. In addition to a few drug-derived substances, there were 16 and 13 identified metabolites with significant differences between the diagnoses in SF and IFP, respectively. The pathways downregulated in RA included androgen, bile acid, amino acid, and histamine metabolism, and those upregulated included biotin metabolism in pOA and purine metabolism in RA and pOA. The RA-induced downregulation of androgen and bile acid metabolism was observed for both SF and IFP. The levels of 11 lipid metabolites, mostly glycerophospholipids and fatty acid amides, were also altered by these inflammatory conditions. The identified metabolic pathways could be utilized in the future to deepen our understanding of the pathogeneses of OA and RA and to develop not only biomarkers for their early diagnosis but also therapeutic targets.
34870735 Usefulness of noninvasive diagnostic procedures for assessment of methotrexate hepatotoxic 2022 Apr Methotrexate (MTX) is recommended as a first-line treatment for rheumatoid arthritis (RA). There are no strict guidelines regarding monitoring for liver damage in RA patients. This study aimed to evaluate noninvasive diagnostic procedures in assessing liver fibrosis in RA patients. Ninety-six RA patients were recruited for this study. The procollagen III N-terminal peptide (PIIINP) serum level was measured in all patients. The Enhanced Liver Fibrosis score (ELF-1) was calculated for 82 patients. Transient elastography (TE) was performed in 91 patients, those examined were divided into two groups: a study and control group, comprising patients with and without risk factors for liver fibrosis, respectively. The TE result correlated only with the body mass index-BMI (p < 0.05); there was no correlation with the cumulative MTX dose (p = 0.33). The TE result was significantly higher in those with risk factors for liver fibrosis than in those without risk factors (TE result >  = 7.1 kPa 28/42 vs 13/41, HR = 2.103, Mann-Whitney U test, approximately 0.02). There was a positive correlation between the PIIINP level and body weight (p = 0.028), cumulative MTX dose (p = 0.007), RA activity (p = 0.028) and diabetes mellitus (DM) (p = 0.001). There was a positive correlation between the ELF-1 score and age (p < 0.001), cumulative MTX dose (p = 0.007) and RA activity (p < 0.001). The PIIINP level and ELF-1 score are not organ specific, and readings may vary depending on RA activity. TE is organ specific and can be performed by a skilled ultrasonographer might be useful to assess actual liver condition.
35006451 Incidence and risk factors for vertebral fracture in rheumatoid arthritis: an update meta- 2022 May OBJECTIVES: This study was conducted to investigate the prevalence of vertebral fracture (VF) and its risk in patients with rheumatoid arthritis (RA) as compared to healthy individuals, and to explore the underlying risk factors. METHODS: The electronic databases of PubMed, EMBASE, and the Cochrane Library were applied to search for the relevant literatures, which reported the prevalence of VF in both RA patients and healthy controls (up to Mar 31, 2021). The non-weighted prevalence of VF, pooled estimates of odds ratio (OR), and its 95% confidence intervals (CI) were calculated with the use of random-effects model; between-study heterogeneity was evaluated by Cochrane Q statistic, then was quantified with I(2). Publication bias was evaluated using Egger's linear regression test. RESULTS: A number of 867 literatures were identified after searching for online databases, based on the inclusion and exclusion criteria, 11 eligible studies, which comprising 3805 RA patients and 59,517 healthy participants, were finally incorporated in meta-analysis. The results showed that RA patients had an increased prevalence of VF (20.29 vs 8.63%), and an elevated risk for VF (OR = 3.04, 95% CI 1.97-4.71) as compared to healthy population. Additional subgroup analysis suggested that age, body mass index (BMI), disease activity, and drug therapy might be associated with risk of VF in RA. CONCLUSIONS: Overall, our study demonstrated an increased risk of VF in patients with RA, suggesting that age, race, BMI, disease activity, and drug therapy may be represented as risk factors contributing to the occurrence of VF in RA. Key Points • RA patients had the increased prevalence and risk of vertebral fracture (VF) as compared to healthy population. • Age, race, BMI, disease activity, and drug therapy might be associated with VF in RA. • Our findings would be helpful for the early evaluation of RA patients with high VF risk.
35048562 Association of Polygenic Risk Scores With Radiographic Progression in Patients With Rheuma 2022 May OBJECTIVE: To investigate whether polygenic risk scores obtained using data from a genome-wide association study (GWAS) of rheumatoid arthritis (RA) susceptibility can be predictors of radiographic progression. METHODS: We constructed polygenic risk scores using GWAS summary data on associations of single-nucleotide polymorphisms with RA susceptibility. The polygenic risk scores were stratified into quintiles based on levels of significance (ranging from top quintile of polygenic risk scores to bottom quintile). In addition, change in the Sharp/van der Heijde score (SHS) of radiographic progression over the first 5 years after onset of RA was assessed. The change in SHS over 5 years was stratified according to quartiles, with the top quartile of change in SHS defined as severe radiographic progression (score change of >35 points) and the remaining 3 quartiles defined as nonsevere radiographic progression. Polygenic risk scores were assessed for their ability to predict the SHS status over 5 years in a training set (n = 500 RA patients) for selection of the best model, and in a testing set (n = 740 RA patients) for validation of the data. We evaluated the performance of the polygenic risk score as a predictor of severe radiographic progression in univariable and multivariable analyses with inclusion of other factors. RESULTS: Polygenic risk scores constructed from 43,784 single-nucleotide polymorphisms significantly differed between patients who experienced severe radiographic progression and those with nonsevere radiographic progression in both the training set (P = 0.0064) and the testing set (P = 0.017). Patients with polygenic risk scores in the top quintile had a higher risk of severe progression compared to those with polygenic risk scores in the bottom quintile (odds ratio [OR] 1.90, P = 0.0022), and the risk of severe radiographic progression was even higher when restricted to patients who were younger at disease onset (OR 5.06, P = 0.00038). The group with polygenic risk scores in the top quintile and the anti-citrullinated protein antibody (ACPA)-positive group had significantly higher proportions of patients with severe radiographic progression (P = 0.00052 and P = 0.0022, respectively) compared to the remaining groups. Multivariable analysis showed that polygenic risk score (P = 0.00019) as well as female sex (P = 0.0033), ACPA positivity (P = 0.0023), and body mass index (P = 0.024) were independent risk factors for severe radiographic progression. CONCLUSION: A polygenic risk score that is derived from GWAS data on RA susceptibility is associated with the level of severity of radiographic progression in patients with RA.
34767108 Machine learning to identify immune-related biomarkers of rheumatoid arthritis based on WG 2022 Apr OBJECTIVES: This study was designed to identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and to explore the potential pathological relevance of immune cell infiltration in this disease. METHODS: Three previously published datasets containing gene expression data from 35 RA patients and 29 controls (GSE55235, GSE55457, and GSE12021) were downloaded from the GEO database, after which a weighted correlation network analysis (WGCNA) approach was utilized to clarify differentially abundant genes. Candidate biomarkers of RA were then identified via the use of a LASSO regression model and support vector machine recursive feature elimination (SVM-RFE) analyses. Data were validated based upon the area under the receiver operating characteristic curve (AUC) values, with hub genes being identified as those with an AUC > 85% and a P value < 0.05. Lastly, the CIBERSORT algorithm was used to assess immune cell infiltration of RA tissues, and correlations between immune cell infiltration and disease-related diagnostic biomarkers were assessed. RESULTS: The green-yellow module containing 87 genes was found to be highly correlated with RA positivity. FADD, CXCL2, and CXCL8 were identified as potential RA diagnostic biomarkers (AUC > 0.85), and these results were validated using the GSE77298 dataset. Immune cell infiltration analyses revealed the expression of hub genes to be correlated with mast cells, monocytes, activated NK cells, CD8 T cells, resting dendritic cells, and plasma cells. CONCLUSION: These data indicate that FADD, CXCL2, and CXCL8 are valuable diagnostic biomarkers of RA, offering new insight that can guide future studies of RA incidence and progression.
34837524 The effect of flaxseed with or without anti-inflammatory diet in patients with rheumatoid 2022 Apr PURPOSE: Beneficial effect of long-chain ω-3 fatty acids against symptoms of rheumatoid arthritis (RA) has been indicated in previous studies. We examined the effect of flaxseed and anti-inflammatory diet in patients with RA. METHODS: The 12-week intervention was performed on 120 patients with RA who were randomized to three groups of flaxseed (30 g/day) plus anti-inflammatory diet (AIF group), flaxseed (30 g/day) plus regular diet (RF group), and roasted wheat (30 g/day) plus regular diet (RW group). Disease Activity Score 28-joints (DAS28), health assessment questionnaire (HAQ) disability and pain, quality of life, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor, and anti-cyclic citrullinated peptides (anti-CCP) were measured before and after trial. Analysis was performed using per-protocol and intention-to-treat (ITT) approaches. RESULTS: One hundred and two patients completed the protocol. Flaxseed decreased DAS28 in RF group compared to RW (- 0.87 ± 1.11 vs. - 0.24 ± 0.78; P = 0.014). Pain severity (P ≤ 0.001), morning stiffness (P < 0.05), and disease feeling (P < 0.01) decreased significantly in AIF and RF groups. HAQ disability and quality of life measurements improved in all 3 groups, with a greater extent in AIF and RF groups (P < 0.001) compared to RW. Between-group differences were significant for DAS28, pain scores, and physical and mental health variables. ESR, CRP, anti-CCP, and rheumatoid factor were not different between groups. Results of ITT analysis did not cause much difference. CONCLUSIONS: In conclusion, flaxseed may be used as a helpful adjuvant therapy for patients with RA. Calls are open for examining the effect of anti-inflammatory diet on RA symptoms. TRIAL REGISTRATION NUMBER: Registered at irct.ir as IRCT20190923044858N1, February 6, 2020.
34376384 Trajectory clusters of radiographic progression in patients with rheumatoid arthritis: ass 2022 Feb OBJECTIVES: Identification of trajectories of radiographic damage in rheumatoid arthritis (RA) by clustering patients according to the shape of their curve of Sharp-van der Heijde scores (SHSs) over time. Developing models to predict their progression cluster from baseline characteristics. METHODS: Patient-level data over a 2-year period from five large randomised controlled trials on tumour necrosis factor inhibitors in RA were used. SHSs were clustered in a shape-respecting manner to identify distinct clusters of radiographic progression. Characteristics of patients within different progression clusters were compared at baseline and over time. Logistic regression models were developed to predict trajectory of radiographic progression using information at baseline. RESULTS: In total, 1887 patients with 7738 X-rays were used for cluster analyses. We identified four distinct clusters with characteristic shapes of radiographic progression: one with a stable SHS over the whole 2-year period (C0/lowChange; 86%); one with relentless progression (C1/rise; 5.8%); one with decreasing SHS (C2/improvement; 6.9%); one going up and down (C3/bothWays; 1.4%) of the SHS. Robustness of clusters were confirmed using different clustering methods. Regression models identified disease duration, baseline C-reactive protein (CRP) and SHS and treatment status as predictors for cluster assignment. CONCLUSIONS: We were able to identify and partly characterise four different clusters of radiographic progression over time in patients with RA, most remarkably one with relentless progression and another one with amelioration of joint damage over time, suggesting the existence of distinct patterns of joint damage accrual in RA.
33705243 Clinicopathological characteristics of lymphoproliferative disorders in 232 patients with 2022 Jan 5 OBJECTIVE: To describe the clinicopathological characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter case series, we retrospectively reviewed the medical records of RA patients who were newly diagnosed as having LPDs with or without biopsy confirmation between 2000 and 2017 in eight hospitals in Japan. RESULTS: We included 232 patients with LPDs. The median age was 67 years (interquartile range [IQR], 60-73 years), and 77.1% were female. At the time of LPD diagnosis, 94.8% and 62.6% of the patients were methotrexate users and in remission or had low RA disease activity, respectively; lymphadenopathy and extranodal involvement were present in 77.1% and 51.9%, respectively. Major extranodal sites were the lungs and oral/oropharyngeal mucosa. The most common LPD pathological subtype was diffuse large B-cell lymphoma (40.5%), followed by classic Hodgkin lymphoma (10.8%), Epstein-Barr virus-positive mucocutaneous ulcer (7.7%), and reactive lymphoid hyperplasia (6.2%). The clinical and laboratory characteristics varied across the pathological subtypes. CONCLUSION: LPD occurred mainly in methotrexate users, while RA disease activity did not seem to be associated with LPD development. Although the clinical manifestations vary among pathological subtypes, manifestations of LPD in patients with RA can include lymphadenopathy, extranodal mass, and mucocutaneous ulcer.