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ID PMID Title PublicationDate abstract
33713887 Mitochondrial N-formyl methionine peptides associate with disease activity as well as cont 2021 May OBJECTIVES: Literature suggests that neutrophils of patients with rheumatoid arthritis (RA) are primed to respond to N-formyl methionine group (formylated peptides). Animal models indicate that formylated peptides contribute to joint damage via neutrophil recruitment and inflammation in joints. Non-steroidal anti-inflammatory drugs are also known to inhibit formyl peptide-induced neutrophil activation. The predominant source of formylated peptides in sterile inflammatory conditions like RA is mitochondria, organelles with prokaryotic molecular signatures. However, there is no direct evidence of mitochondrial formyl peptides (mtNFPs) in the circulation of patients with RA and their potential role in neutrophil-mediated inflammation in RA, including their clinical significance. METHODS: Levels of mtNFPs (total fMet, MT-ND6) were analyzed using ELISA in plasma and serum obtained from patients in 3 cross-sectional RA cohorts (n = 275), a longitudinal inception cohort (n = 192) followed for a median of 8 years, and age/gender-matched healthy controls (total n = 134). Neutrophil activation assays were done in the absence or presence of formyl peptide receptor 1 (FPR1) inhibitor cyclosporine H. RESULTS: Elevated levels of total fMet were observed in the circulation of patients with RA as compared to healthy controls (p < 0.0001) associating with disease activity and could distinguish patients with the active disease from patients with inactive disease or patients in remission. Baseline levels of total fMet correlated with current and future joint involvement, respectively and predicted the development of rheumatoid nodules (OR = 1.2, p = 0.04). Further, total fMet levels improved the prognostic ability of ACPA in predicting erosive disease (OR of 7.9, p = 0.001). Total fMet levels correlated with markers of inflammation and neutrophil activation. Circulating mtNFPs induced neutrophil activation in vitro through FPR1-dependent mechanisms. CONCLUSIONS: Circulating mtNFPs could be novel biomarkers of disease monitoring and prognosis for RA and in investigating neutrophil-mediated inflammation in RA. We propose, FPR1 as a novel therapeutic target for RA.
33397472 Younger age and female gender are determinants of underestimated cardiovascular risk in rh 2021 Jan 4 BACKGROUND: Rheumatoid arthritis (RA) patients have an increased cardiovascular (CV) risk. Here, we aimed to investigate whether gender and age are contributing to the misclassification of CV risk in RA patients. METHODS: Prospectively collected data on cardiovascular risk factors and incident events from the Nijmegen inception cohort were analyzed, with up to 10 years follow-up. Original as well as the EULAR-modified (M)_SCORE algorithms were used to calculate CV risk. Patients were stratified in deciles according to predicted risk; the Hosmer-Lemeshow test was used to check concordance between observed and predicted risk, in subgroups of gender and age. RESULTS: There were 863 RA patients included with 128 incident CV events. When using SCORE in the whole group, there was evidence of a discrepancy between the predicted and observed CV risk (H-L test p < 0.003), mainly present in the female subgroup (H-L test p < 0.001). Interestingly, 36% of females who developed an event belonged to the low CV risk group, whereas this was just 10% in RA males. When analyzing the subgroups based on age, a discrepancy was present only in the youngest patients (H-L test p < 0.001 in patients < 55 years) consisting of an underestimation of CV risk (5.3% predicted vs. 8.0% observed). Similar results were obtained when the M_SCORE was applied. CONCLUSION: CV risk is especially underestimated in female and younger RA patients. This suggests that modifying the weight for the female gender and/or younger age in currently used CV risk algorithms might improve their predictive value in RA, contributing to better CV risk management.
34135114 Value of imaging detected joint inflammation in explaining fatigue in RA at diagnosis and 2021 Jun OBJECTIVE: Fatigue in rheumatoid arthritis (RA) is hypothesised to be caused by inflammation. Still ~50% of the variance of fatigue in RA cannot be explained by the Disease Activity Score (DAS), nor by background or psychological factors. Since MRI can detect joint inflammation more sensitively than the clinical joint counts as incorporated in the DAS, we hypothesised that inflammation detected by MRI could aid in explaining fatigue in RA at diagnosis and during the follow-up. METHODS: 526 consecutive patients with RA were followed longitudinally. Fatigue was assessed yearly on a Numerical Rating Scale. Hand and foot MRIs were performed at inclusion, after 12 and 24 months in 199 patients and were scored for inflammation (synovitis, tenosynovitis and osteitis combined). We studied whether patients with RA with more MRI-inflammation were more fatigued at diagnosis (linear regression), whether the 2-year course of MRI-inflammation associated with the course of fatigue (linear mixed models) and whether decrease in MRI-inflammation in year 1 associated with subsequent improvement in fatigue in year 2 (cross-lagged models). Similar analyses were done with DAS as inflammation measure. RESULTS: At diagnosis, higher DAS scores were associated with more severe fatigue (p<0.001). However, patients with more MRI-inflammation were not more fatigued (p=0.94). During 2-year follow-up, DAS decrease associated with improvement in fatigue (p<0.001), but MRI-inflammation decrease did not (p=0.96). DAS decrease in year 1 associated with fatigue improvement in year 2 (p=0.012), as did MRI-inflammation decrease (p=0.039), with similar effect strength. CONCLUSION: Sensitive measurements of joint inflammation did not explain fatigue in RA at diagnosis and follow-up. This supports the concept that fatigue in RA is partly uncoupled from inflammation.
34155572 Quantification of bone marrow edema in rheumatoid arthritis by using high-speed T2-correct 2021 Nov OBJECTIVE: To determine whether high-speed T2-corrected multiecho (HISTO) sequences can quantify bone marrow edema (BME) in the capitate bone in rheumatoid arthritis (RA), and whether the HISTO fat fraction (FF) reflects therapeutic effectiveness. METHODS: In this prospective study, 25 RA patients (19 women; average age, 45.08 ± 13.48 years) underwent 3.0-T MRI with HISTO at the baseline and after 4, 8, and 12 weeks of treatment. Rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet (PLT) count, and 28-joint Disease Activity Score using ESR (DAS28-ESR) were recorded on the day of each MRI examination by a rheumatologist blinded to the MRI findings. In addition, 21 healthy subjects (15 women; age, 49.17 ± 6.56 years) underwent only the HISTO sequence at a single time point. RESULTS: HISTO FF values were significantly higher in the control group (74.5% ± 3.1%; range, 68.6-79.3%) than in the patient group (55.8% ± 17.7%; range, 15.6-79.0%) at the baseline (independent-samples t-test: t = 5.257, P = 0.000). The changes in HISTO FF and DAS28-ESR showed moderate negative correlations with each other at 4, 8, and 12 weeks, and all of them were statistically significant (P < 0.05). As the HISTO FF increased, the DAS28-ESR decreased. CONCLUSION: The HISTO sequence can measure the bone marrow FF of the wrist joint bones in RA patients. The HISTO FF value increased as the DAS28-ESR decreased. The HISTO sequence may help quantify BME in RA and help monitor the effectiveness of RA treatment. Key Points •The HISTO sequence could measure the bone marrow FF of the wrist joint bones. •FF value increased as the DAS28-ESR decreased in RA patients. •The HISTO sequence can monitor the therapeutic effect of RA.
33547580 Is there an association between rheumatoid arthritis and bone changes in the temporomandib 2021 May OBJECTIVES: Evaluate the relation of rheumatoid arthritis (RA) and bone changes in the temporomandibular joint diagnosed by cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This systematic review and meta-analysis were recorded in the PROSPERO database, using the CRD42020153246 protocol. The electronic searches were performed in the following databases: Pubmed, Scopus, Web of Science, Lilacs, Cochrane, and Open Grey. Cross-sectional studies that evaluated patients with RA with bone changes in the temporomandibular joint diagnosed by CBCT, without language restriction or publication date, were included. Meta-analysis was performed in Stata Software (StataCorp, TX, USA, version 12.0), using the metan, and a random effects model, and the risk of different bone alterations occurring in adults with and without arthritis was estimated using odds ratios (ORs) as a pooled measure of effect. Forest plots were used to present the isolated and the pooled effects (ORs and 95% CI). RESULTS: Six studies were used for qualitative synthesis and 2 studies for quantitative synthesis. All studies diagnosed higher prevalence changes in the bone structures of the TMJ of RA patients, described as erosion, flattening, sclerosis, and osteophytes. Meta-analysis showed that the chance of bone changes occurring in components of the TMJ is greater in individuals who have RA. CONCLUSION: There is an association between RA and bone changes in TMJ structures diagnosed through CBCT, as RA patients were more likely to have osteoarthritic changes in this joint. CLINICAL RELEVANCE: Understanding the existence of an association between bone alterations in TMJ and RA can assist in the management of patients.
34331261 Nanomedicine-based combination of dexamethasone palmitate and MCL-1 siRNA for synergistic 2021 Dec The main aim of this research was to design a MCL-1 siRNA and dexamethasone (DEX)-loaded folate modified poly(lactide-co-glycolide) (PLGA)-based polymeric micelles with an eventual goal to improve the therapeutic outcome in the rheumatoid arthritis (RA). Polymeric micelles encapsulating the MCL-1 siRNA and DEX was successfully developed and observed to be stable. Physicochemical characteristics such as particle size and particle morphology were ideal for the systemic administration. Folate-conjugated DEX/siRNA-loaded polymeric micelles (DS-FPM) significantly lowered the MCL-1 mRNA expression compared to either DEX/siRNA-loaded polymeric micelles (DS-PM) or free siRNA in Raw264.7 cells and macrophage cells suggesting the importance of targeted nanocarriers. Most importantly, DS-FPM exhibited a greatest decrease in the hind paw volume with lowest clinical score compared to any other treated group indicating a superior anti-inflammatory activity. DS-FPM showed significantly lower levels of the TNF-α and IL-1β compared to AIA model and free groups. The folate receptor (FR)-targeting property of DS-FPM has been demonstrated to be a promising delivery platform for the effective delivery of combination therapeutics (siRNA and DEX) toward the treatment of rheumatoid arthritis.
34132852 Prevalence of Sarcopenia and its Association with Antirheumatic Drugs in Middle-Aged and O 2021 Nov To examine the prevalence of sarcopenia and its association with antirheumatic drugs in adults with rheumatoid arthritis (RA). This review was registered on PROSPERO and followed PRISMA guidelines. Electronic databases were searched for studies reporting on the prevalence of sarcopenia in adults with RA using any muscle index (muscle mass, strength and/or physical performance) and cutpoints as recommended by established criteria (EWGSOP1/2, AWGS, FNIH, SDOC). The secondary objective was to investigate the relationship between RA, antirheumatic drugs, and sarcopenia. Among 2240 middle-aged and older adults with RA (mean age: 47.7 ± 5.5 to 75.0 ± 6.2 years, 83.8% women), the pooled prevalence of low muscle mass/sarcopenia was 30.2% [95% confidence interval (CI) 24.2-36.2%; 16 studies; I(2): 89.2%]. Sub-group analysis showed a non-significant higher prevalence of low muscle mass alone (32.6%, 95% CI 25.0-40.3%; I(2): 87.9%) versus consensus definitions of sarcopenia (25.4%, 95% CI 15.4-35.3%; I(2): 91.2%, p = 0.255). In adults with RA, corticosteroid use was positively associated with sarcopenia [odds ratio (OR) 1.46, 95% CI 0.94-2.29, 7 studies; I(2): 47.5%] while conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was inversely associated (OR 0.70, 95% CI 0.52-0.94; 6 studies: I(2): 0.00%) with this muscle disease. No association was found for biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (OR 0.83, 95% CI 0.54-1.30; 6 studies: I(2): 47.6%). Sarcopenia is a common comorbidity of RA, and as such, clinicians should screen for this muscle disease in adults with RA. Further longitudinal studies are needed to understand the role of antirheumatic drugs (particularly type, dosing, and duration) in the development of sarcopenia.
34625107 Photodynamic therapy for synovial hyperplasia in patients with refractory rheumatoid arthr 2021 Oct 9 BACKGROUND: Persistent synovial hyperplasia with inflammation in rheumatoid arthritis is one of the main pathogeneses of refractory rheumatoid arthritis (RRA). Photodynamic therapy (PDT) causes less trauma than steroid injections or arthroscopic synovectomy while providing stronger targeting and more durable curative effects. The aim of this trial was to evaluate the short-, medium-, and long-term clinical efficacy of PDT when applied as a treatment for RRA synovial hyperplasia and synovitis. METHODS AND ANALYSIS: This protocol is for a single-center, randomized, double-blind, blank-controlled prospective trial. A sample of 126 RRA patients will be randomly divided into 3 groups: the control group, the "PDT once" group, and the "PDT twice" group, with 42 participants per group. The trial will be conducted by the Rheumatology and Immunology Department of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University. The Ultrasound Compound Score of Synovitis (UCSS) has been selected as the primary outcome measure. The secondary outcome measures include knee joint clinical assessments, ratio of relapse, duration of remission, Disease Activity Score in 28 joints (DAS28), inflammation indexes, serum concentrations of specific antibodies, and changes in articular structures as detected by X-ray scans in the 48th week. The improvement ratios of the UCSS at the 8th, 24th, and 48th weeks (compared with baseline) reflect short-, medium-, and long-term time frames, respectively. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Ethics Committee of the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, China (Approval No. granted by the ethics committee: NFZXYEC-2017-005) and then entered in the Chinese Clinical Trials Registry under registration number ChiCTR1800014918 (approval date: February 21, 2018). All procedures are in accordance with Chinese laws and regulations and with the Declaration of Helsinki by the World Medical Association (WMA). Any modifications of this protocol during execution will need additional approval from the Ethics Committee of our hospital. TRIAL REGISTRATION NUMBER: ChiCTR1800014918 .
33691660 Fear-of-falling and associated risk factors in persons with rheumatoid arthritis: a 1 ye 2021 Mar 10 BACKGROUND: Falls, associated injuries and fear-of-falling are common in adults with RA. Fear-of-falling can be a major consequence of, and as debilitating as falling, resulting in a cycle of activity restriction, reduced quality of life, institutionalisation and potentially increase risk of falls. The objective of this study was to examine the relationship between fear-of-falling and risk factors associated with fear-of-falling in adults with rheumatoid arthritis (RA) over a 1 year period. METHODS: Five hundred fifty-nine patients with RA were recruited from four outpatient clinics in this prospective cohort study. Baseline assessments included socio-demographic, medical and lifestyle related risk factors. Fall incidence was prospectively obtained monthly using postal cards over a 1 year period. Fear-of-falling was assessed at baseline and 1 year using the Short Falls Efficacy Scale-International (Short FES-I). Logistic regression was used to determine the association between high fear-of-falling (Short FES-I > 11) at baseline (outcome) and a range of putative predictor variables including previous falls, and also baseline factors associated with a high fear-of-falling at follow-up. RESULTS: Five hundred thirty-five (ninety-six percent) participants (mean age 62.1 yrs.; 18-88 yrs) completed 1 year follow-up and of these, 254 (47%) completed the Short FES-I questionnaire at 1 year. In a multivariate model, a history of multiple falls (OR = 6.08) higher HAQ score (OR = 4.87) and increased time to complete the Chair Stand Test (OR = 1.11) were found to be independent predictors of high fear-of-falling and had an overall classification rate of 87.7%. There were no significant differences found in fear-of-falling at 1 year follow-up in those who reported falls during the study, participant's baseline fear appeared to predict future fear, regardless of further falls. CONCLUSIONS: Fear-of-falling is significantly associated with previous falls and predictive of future falls and fear. RA patients would benefit from fall prevention measures whether or not they have previously fallen.
34737738 Applicability of Small-Molecule Inhibitors in the Study of Peptidyl Arginine Deiminase 2 ( 2021 Citrullination, the conversion of peptidyl-arginine into peptidyl-citrulline, is involved in the breakage of self-tolerance in anti-CCP-positive rheumatoid arthritis. This reaction is catalyzed by peptidyl arginine deiminases (PADs), of which PAD2 and PAD4 are thought to play key pathogenic roles. Small-molecule PAD inhibitors such as the pan-PAD inhibitor BB-Cl-amidine, the PAD2-specific inhibitor AFM-30a, and the PAD4-specific inhibitor GSK199 hold therapeutic potential and are useful tools in studies of citrullination. Using an ELISA based on the citrullination of fibrinogen, we found that AFM-30a inhibited the catalytic activity of PADs derived from live PMNs or lysed PBMCs and PMNs and of PADs in cell-free synovial fluid samples from RA patients, while GSK199 had minor effects. In combination, AFM-30a and GSK199 inhibited total intracellular citrullination and citrullination of histone H3 in PBMCs, as determined by Western blotting. They were essentially nontoxic to CD4(+) T cells, CD8(+) T cells, B cells, NK cells, and monocytes at concentrations ranging from 1 to 20 μM, while BB-Cl-amidine was cytotoxic at concentrations above 1 μM, as assessed by flow cytometric viability staining and by measurement of lactate dehydrogenase released from dying cells. In conclusion, AFM-30a is an efficient inhibitor of PAD2 derived from PBMCs, PMNs, or synovial fluid. AFM-30a and GSK199 can be used in combination for inhibition of PAD activity associated with PBMCs but without the cytotoxic effect of BB-Cl-amidine. This suggests that AFM-30a and GSK199 may have fewer off-target effects than BB-Cl-amidine and therefore hold greater therapeutic potential.
32602263 Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift. 2021 Feb Rheumatoid arthritis (RA) is currently diagnosed and treated when an individual presents with signs and symptoms of inflammatory arthritis (IA) as well as other features, such as autoantibodies and/or imaging findings, that provide sufficient confidence that the individual has RA-like IA (e.g., meeting established classification criteria) that warrants therapeutic intervention. However, it is now known that there is a stage of seropositive RA during which circulating biomarkers and other factors (e.g., joint symptoms) can be used to predict if and when an individual who does not currently have IA may develop future clinically apparent IA and classifiable RA. Indeed, the discovery of the "pre-RA" stage of seropositive disease has led to the development of several clinical trials in which individuals are studied to identify ways to delay or prevent the onset of clinically apparent IA/RA. This review focuses on several issues pertinent to understanding the prevention of RA. These include discussion of the pathogenesis of pre-RA development, prediction of the likelihood and timing of future classifiable RA, and a review of completed and ongoing clinical trials in RA prevention. Furthermore, this review discusses challenges and opportunities to be addressed to effect a paradigm shift in RA, where in the near future, proactive risk assessment focused on prevention of RA will become a public health strategy in much the same manner as cardiovascular disease is managed today.
32243209 Severe joint deformity and patient global assessment of disease are associated with discre 2021 Mar OBJECTIVE: Although recent clinical trials showed that ultrasound (US) remission is not required to achieve good outcomes at the group level, it currently remains unclear whether the prognosis of individual patients in clinical remission, but not US remission, i.e. those with subclinical sonographic synovitis (SSS), is favorable. However, it is no longer acceptable to perform US on all patients in order to identify those with SSS. Therefore, the present study was initiated to elucidate the conditions under which SSS is frequently detected. METHODS: In total, 563 consecutive RA patients were recruited. Bilateral 2-5 MCP, wrist, ankle, and 2-5 MTP joints were scanned by US, and Gray scale and Power Doppler (PD) images were scored semi-quantitatively. Clinical data were obtained by physicians who were blind to US results. Changes in the modified Total Sharp Score (mTSS) of tocilizumab (TCZ) users were calculated. RESULTS: A total of 402 patients were included. SSS was more frequently detected in patients with more severe joint deformity, even if they were in remission. In contrast, a high Patient Global Assessment of Disease (PtGA) did not reflect SSS. Furthermore, the relationship between PtGA and PD scores was weak. Although the frequency of SSS was high in TCZ user, the presence of SSS in TCZ users not always results in the progression of mTSS. CONCLUSIONS: While remission is overestimated in patients with severe joint deformity, underestimations may occur in those who do not fulfill remission criteria because of a high PtGA.
33155543 Tocilizumab preserves renal function in rheumatoid arthritis with AA amyloidosis and end-s 2021 Jan Case 1: A 59-year-old Japanese woman with rheumatoid arthritis (RA) for 36 years was admitted for evaluation of deteriorating renal function. Her serum creatine was 4.2 mg/dL, and proteinuria was 6.5 g daily. Renal and duodenal biopsy revealed AA amyloidosis. After treatment with tocilizumab (a humanized anti-interleukin-6 receptor antibody), proteinuria decreased to 1.1 g daily. The patient's renal function subsequently remained stable for 8 years. Case 2: A 71-year-old Japanese man with RA for 30 years was admitted due to deterioration of renal function. Serum creatine was 2.9 mg/dL, and urinary protein excretion was 0.06 g daily. Renal and duodenal biopsy identified AA amyloidosis. Tocilizumab was initiated, and his renal function remained stable for 6 years. The 2(nd) duodenal biopsy showed a marked decrease of AA amyloid deposits. Conclusion: These two cases suggest that tocilizumab may preserve renal function in the setting of end-stage kidney disease and shift the point of no return for RA patients with AA amyloidosis and renal dysfunction.
32715341 Cross-cultural adaptation and psychometric testing of the Dutch and German versions of the 2021 May The Evaluation of Daily Activity Questionnaire (EDAQ) is a detailed patient-reported outcome measure of activity ability. The objective of this research was to assess the linguistic and cross-cultural validity and psychometric properties of the EDAQ in rheumatoid arthritis for Dutch and German speakers. The EDAQ was translated into Dutch and German using standard methods. A total of 415 participants (Dutch n = 252; German n = 163) completed two questionnaires about four weeks apart. The first included the EDAQ, Health Assessment Questionnaire (HAQ) and 36-item Short-Form v2 (SF-36v2) and the second, the EDAQ only. We examined construct validity using Rasch analysis for the two components (Self-Care and Mobility) of the Dutch and German EDAQ. Language invariance was also tested from the English version. We examined internal consistency, concurrent and discriminant validity and test-retest reliability in the 14 EDAQ domains. The Self-Care and Mobility components satisfied Rasch model requirements for fit, unidimensionality and invariance by language. Internal consistency for all 14 domains was mostly good to excellent (Cronbach's alpha ≥ 0.80). Concurrent validity was mostly strong: HAQ r(s) = 0.65-0.87; SF36v2 r(s) = - 0.61 to - 0.87. Test-retest reliability was excellent [ICC (2,1) = 0.77-0.97]. The EDAQ has good reliability and validity in both languages. The Dutch and German versions of the EDAQ can be used as a measure of daily activity in practice and research in the Netherlands and German- speaking countries.
33668234 Review of Wearable Sensor-Based Health Monitoring Glove Devices for Rheumatoid Arthritis. 2021 Feb 24 Early detection of Rheumatoid Arthritis (RA) and other neurological conditions is vital for effective treatment. Existing methods of detecting RA rely on observation, questionnaires, and physical measurement, each with their own weaknesses. Pharmaceutical medications and procedures aim to reduce the debilitating effect, preventing the progression of the illness and bringing the condition into remission. There is still a great deal of ambiguity around patient diagnosis, as the difficulty of measurement has reduced the importance that joint stiffness plays as an RA identifier. The research areas of medical rehabilitation and clinical assessment indicate high impact applications for wearable sensing devices. As a result, the overall aim of this research is to review current sensor technologies that could be used to measure an individual's RA severity. Other research teams within RA have previously developed objective measuring devices to assess the physical symptoms of hand steadiness through to joint stiffness. Unfamiliar physical effects of these sensory devices restricted their introduction into clinical practice. This paper provides an updated review among the sensor and glove types proposed in the literature to assist with the diagnosis and rehabilitation activities of RA. Consequently, the main goal of this paper is to review contact systems and to outline their potentialities and limitations. Considerable attention has been paid to gloved based devices as they have been extensively researched for medical practice in recent years. Such technologies are reviewed to determine whether they are suitable measuring tools.
33978821 IL-23R gene polymorphisms in rheumatoid arthritis. 2022 Mar Rheumatoid arthritis (RA) is a common autoimmune disease in which many different genetic variants of functional gene polymorphisms may play a culprit role in the underlying pathogenetic mechanism. The recent studies suggest that interleukin-23 receptor (IL-23R) gene polymorphisms may increase susceptibility to the development of various autoimmune diseases. We aimed to examine the possible relationship of nine single nucleotide polymorphisms (SNPs) in the IL-23R gene to susceptibility to rheumatoid arthritis and their associations with disease characteristics in the South Aegean region of Turkey. We enrolled 100 rheumatoid arthritis patients and age- and sex-matched 96 healthy subjects in the study. After deoxyribonucleic acid (DNA) isolation was performed, a 'Restriction Fragment Length Polymorphism' (RFLP) method was used for the investigation of polymorphisms associated with the IL-23R gene. Allele identification and genotyping were obtained from polymerase chain reaction (PCR) products using gel electrophoresis. Allele frequencies and detected genotypes were compared between groups. All statistical analyses were performed using SPSS 25.0 (IBM SPSS Statistics 25 software (Armonk, NY: IBM Corp.)). Continuous variables were defined by the mean ± standard deviation and categorical variables were defined by number and percent. Logistic Regression Analysis was used for determining which variables affect the presence of RA. Differences between categorical variables were analyzed with Chi-square analysis. Statistical significance was determined as p < 0.05. The mean age was 53.48 ± 11.7 years in the RA group, whereas 52.55 ± 12.7 years in the healthy control group. The genotypes of IL-23R with rs11805303(TT), rs10889677(AA), rs1004819(AA), and rs7530511(CT) polymorphisms were seen more often in RA patients than healthy controls. Having the AA genotype of IL-23R rs1004819 and the CT genotype of Il-23R rs7530511 increase the development risk of RA with a statistical significance (OR: 3.416 p = 0.003 and OR: 4.899 p = 0.0001, respectively). RA patients with the CC genotype of Il-23R with rs11805303, the CC genotype with rs10889677, and the TT genotype with rs2201841 of the IL-23R gene had higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels than with other genotypes. RA patients with the CC genotype rs11805303 and the GG genotype rs1004819 of the IL-23R gene had more active disease. Our findings suggest that all of the nine analyzed IL-23R gene polymorphisms are seen more frequently than healthy controls in our study population. Besides, some SNPs were related to higher acute phase reactants and higher disease activity scores.
33130232 New insights into macrophage heterogeneity in rheumatoid arthritis. 2021 Jan Rheumatoid arthritis (RA) is a prototypic autoimmune disease that primarily affects joints. Clinical studies and animal models evidenced that mononuclear phagocytes including monocytes and macrophages are crucial to RA pathogenesis, contributing to inflammation and destruction of cartilage and bone. The last decade of research has tremendously changed our view on the origin of tissue-resident macrophages. In light of the recent publications that reveal important phenotypic and functional heterogeneity among macrophages, it is of paramount importance to identify the synovial macrophage subsets that might amplify the inflammatory response or promote the restoration of tissue homeostasis. In this review, we highlight latest studies applying single-cell RNA sequencing that provide deeper insights in macrophage subsets and their putative functions within both human and mouse synovial joint tissue.
33611648 Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rhe 2021 Jun OBJECTIVES: To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution computed tomography (HRCT) PATIENTS AND METHODS: We performed a cross-sectional, observational study in patients with RA-ILD (cases) controlled with a group of RA patients without ILD (controls) paired by sex, age, and time of disease evolution. Patients were assessed using HRCT, PFT, and US. The main variables were B-line number, evaluation of the lung-US score already described, pleural irregularities, and A pattern US lost. ROC curve analysis was performed to establish the cut-off point of the US B-lines number for detecting the presence of significant RA-ILD in relation to HRCT, and logistic regression analysis was performed to identify the intercostal spaces. RESULTS: Seventy-one patients were included, 35 (49.2%) with ILD-RA and 36 (50.8%) RA controls. Regarding US score, we found that the detection of 5.5 lines in a reduced score of 8 intercostal spaces had a sensitivity = 62.2%, specificity = 91.3%, PPV = 88.4%, and NPV = 69.5%. In multivariate analysis, the intercostal spaces which showed independent association with ILD were 3rd right anterior axillary space (OR [IC 95%] 19.0 [1.3-27.5]), 8th right posterior axillary space (OR [IC 95%] 0.04 [0.0-0.6]), 8th right subscapular space (OR [IC 95%] 16.5 [1.8-45.5]), 9th right paravertebral space (OR [IC 95%] 7.11 [1.0-37.1]), and 2nd left clavicular middle space (OR [IC 95%] 21.9 [1.26-37.8]). CONCLUSIONS: Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. A 8-space reduced score showed a similar total predictive capacity than 72-space score. Key Points • Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. • The 72-space evaluation is highly sensitive, whereas a simplified score enables a more specific and faster diagnosis. • The number of B lines is correlated with DLCO, ACPA, inflammatory activity, and physical function.
33336629 Rheumatoid meningitis as a complication of long-standing rheumatoid arthritis: a case trea 2021 Jul Rheumatoid meningitis is a rare complication of long-standing rheumatoid arthritis. We present the case of a 39-year-old Bolivian woman with a history of seropositive rheumatoid arthritis of 12 years of evolution without extra-articular manifestations that develops a severe headache with vomiting. The diagnosis of rheumatoid meningitis was performed based on clinical history, blood count and biochemistry results, cerebrospinal fluid analysis and cranial magnetic resonance imaging findings. High-dose intravenous glucocorticoids were started, followed by rituximab. After treatment, a significant clinical improvement was observed and repeat magnetic resonance imaging scan confirmed an improvement of the meningeal lesions.
33609698 Ginsenoside compound K- a potential drug for rheumatoid arthritis. 2021 Apr Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease, if prescription of effective delayed, the articular disturbances may lead to disability. Ginsenoside compound K (GCK) is the main degradation product of oral ginsenosides in the human intestine. Numerous researches in vitro and in vivo have recorded the anti-arthritic effect of GCK, we discuss the mechanisms from the following three aspects, including anti-inflammatory, immune-regulatory, and bone-protective, respectively, in this review, and the anti-arthritic mechanism of GCK may be related to the effect on TNF-α-TNFR2, glucocorticoid receptor (GR) and β-arrestin1/2. We also describe the anti-anemia effect of GCK to open the possibility that GCK can be used as an effective disease-modifying anti-rheumatic drug (DMARD).