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ID PMID Title PublicationDate abstract
32711580 Does periodontitis affect the treatment response of biologics in the treatment of rheumato 2020 Jul 25 BACKGROUND: Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and the treatment response to biologics in RA patients using FDG-PET/CT. METHODS: Sixty RA patients (male, n = 14; female, n = 46; average age, 58.3 years) treated with biologic agents were included in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The maximum standardized uptake value (SUVmax) was used as a representative value for the assessment of the FDG uptake in periodontal tissue and joints including the bilateral shoulders, elbows, wrists, hip, knees, and ankle joints. The Disease Activity Score (DAS) 28-CRP and the following clinical parameters were assessed: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and matrix metalloproteinase 3 (MMP-3). The relationship between the treatment response of RA and the baseline SUVmax of the periodontal tissue was evaluated. RESULTS: The baseline periodontal SUVmax was related to patient age (r = 0.302, p = 0.009) and the ACPA level (r = 0.265, p = 0.025). The DAS28-CRP, CRP, ESR, MMP-3, and joint SUVmax values were significantly decreased after 6 months of biological therapy. However, the mean periodontal SUVmax, ACPA, and RF showed no significant changes after treatment. There was a significantly negative correlation between the baseline periodontal SUVmax and the treatment response of DAS28-CRP (r = - 0.369, p = 0.004). CONCLUSION: There was a negative correlation between the extent of PD at baseline and the treatment response of RA patients who received biological therapy. The evaluation of the periodontal condition is considered to be an essential part for the management of RA.
31958164 Ultrasound Assessment of Disease Activity Prevents Disease-Modifying Antirheumatic Drug (D 2020 Jul OBJECTIVES: as an objective measure, ultrasound (US) could prevent rheumatoid arthritis (RA) overtreatment induced by concomitant fibromyalgia (FM). Our goal was to study how patients with RA and FM who underwent a US examination differed from those without a US examination in terms of overall disease-modifying antirheumatic drug (DMARD) escalation and biologic DMARD-related direct costs. METHODS: Patients with RA and FM were seen between 2011 and 2017. In cases of 28-joint Disease Activity Score (DAS28) overestimation, patients were referred to undergo a US examination. The US group underwent a US examination to confirm disease activity, and the DAS28 group had disease activity assessment based solely on the DAS28. RESULTS: Of 230 patients with RA, 22 women with RA and FM (DAS28 group, n = 9; and US group, n = 13) were seen in 316 visits (115.68 patient-years). The DMARD treatment was escalated in 27.1% of visits in the DAS28 group versus 17.3% in the US group (P = .046). The relative risk of DMARD escalation in the DAS28 group compared to the US group was 1.57 (95% confidence interval, 1.01-2.43). In sum total, US$240,784.52 were spent on biologics throughout the entire study period. Basing biologic DMARD prescriptions on US results could save an average of US$405.66 per patient-year. CONCLUSIONS: In this real-life study of patients with RA and FM, a US examination was associated with less DMARD escalation and could reduce biologic DMARD direct costs. Specifically, synovitis as scored by power Doppler US could be useful as a treatment target for RA in patients with DAS28 overestimation due to FM, but further studies are necessary.
32580789 A multi-biomarker disease activity score can predict sustained remission in rheumatoid art 2020 Jun 24 BACKGROUND: Reliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission. METHODS: RA patients on > 6 months stable therapy in stable low disease activity (DAS28-ESR ≤ 3.2) were assessed every 3 months for 1 year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as 'low disease activity state' (LDAS). Patients not fulfilling any remission criteria over 1 year were classified as 'persistent disease activity' (PDA). MBDA score was measured at baseline/3/6 months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test. RESULTS: Of 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1 year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68-0.75) and IR/SR (AUROCs 0.65-0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65-0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1 year. CONCLUSIONS: This study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.
33584647 Acid-Sensing Ion Channel-1a in Articular Chondrocytes and Synovial Fibroblasts: A Novel Th 2020 Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H(+)-activated cation channel family. Emerging evidence has suggested that ASIC1a plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). Specifically, ASIC1a could promote inflammation, synovial hyperplasia, articular cartilage, and bone destruction; these lead to the progression of RA, a chronic autoimmune disease characterized by chronic synovial inflammation and extra-articular lesions. In this review, we provided a brief overview of the molecular properties of ASIC1a, including the basic biological characteristics, tissue and cell distribution, channel blocker, and factors influencing the expression and function, and focused on the potential therapeutic targets of ASIC1a in RA and possible mechanisms of blocking ASIC1a to improve RA symptoms, such as regulation of apoptosis, autophagy, pyroptosis, and necroptosis of articular cartilage, and synovial inflammation and invasion of fibroblast-like cells in synovial tissue.
31697380 Association of telomere length with risk of rheumatoid arthritis: a meta-analysis and Mend 2020 May 1 OBJECTIVE: To evaluate the telomere length (TL) in patients with RA relative to that in controls and to test whether TL is causally associated with risk of RA. METHODS: Systematic review and meta-analysis of relevant literature was conducted to evaluate the association between TL and RA. Standardized mean differences with 95% CIs of TL in RA patients relative to controls were pooled using fixed or random-effects models. TL-related single-nucleotide polymorphisms were selected from a genome-wide association study of 37 684 individuals, and summary statistics of RA were obtained from a genome-wide association study meta-analysis including 14 361 RA patients and 43 923 controls. Mendelian randomization was performed using the inverse-variance weighted, weighted-median and likelihood-based methods. Sensitivity analyses were performed to test the robustness of the association. RESULTS: In the meta-analysis of 911 RA patients and 2498 controls, we found that patients with RA had a significantly shorter TL compared with controls (standardized mean differences = -0.50; 95% CI -0.88, -0.11; P = 0.012). In the Mendelian randomization analysis, we found that genetically predicted longer TL was associated with a reduced risk of RA [odds ratio = 0.68; 95% CI 0.54, 0.86; P = 0.002 using the inverse-variance weighted method]. Sensitivity analyses using alternative Mendelian randomization approaches yielded similar findings, suggesting the robustness of the causal association. CONCLUSION: Our study provides evidence for a negative causal association of TL with risk of RA. Further studies are warranted to elucidate the underlying mechanism for the role of telomeres in the development of RA.
32938830 Increased SUMO-activating enzyme SAE1/UBA2 promotes glycolysis and pathogenic behavior of 2020 Sep 17 Fibroblast-like synoviocytes (FLSs) are critical to joint inflammation and destruction in rheumatoid arthritis (RA). Increased glycolysis in RA FLSs contributes to persistent joint damage. SUMOylation, a posttranslational modification of proteins, plays an important role in initiation and development of many diseases. However, the role of small ubiquitin-like modifier-activating (SUMO-activating) enzyme 1 (SAE1)/ubiquitin like modifier activating enzyme 2 (UBA2) in regulating the pathogenic FLS behaviors is unknown. Here, we found an increased expression of SAE1 and UBA2 in FLSs and synovial tissues from patients with RA. SAE1 or UBA2 knockdown by siRNA and treatment with GA, an inhibitor of SAE1/UBA2-mediated SUMOylation, resulted in reduced glycolysis, aggressive phenotype, and inflammation. SAE1/UBA2-mediated SUMOylation of pyruvate kinase M2 (PKM2) promoted its phosphorylation and nuclear translocation and decreased PK activity. Moreover, inhibition of PKM2 phosphorylation increased PK activity and suppressed glycolysis, aggressive phenotype, and inflammation. We further demonstrated that STAT5A mediated SUMOylated PKM2-induced glycolysis and biological behaviors. Interestingly, GA treatment attenuated the severity of arthritis in mice with collagen-induced arthritis and human TNF-α transgenic mice. These findings suggest that an increase in synovial SAE1/UBA2 may contribute to synovial glycolysis and joint inflammation in RA and that targeting SAE1/UBA2 may have therapeutic potential in patients with RA.
32896242 The ovarian reserve as measured by the anti-Müllerian hormone is not diminished in patien 2021 Mar OBJECTIVES: Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Müllerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyse the relationship between fertility in RA female patients and AMH. The aim of present study is to determine the AMH serum concentrations in a long-standing RA patient group and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs. METHODS: Serum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynaecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student's t-test or Mann-Whitney U-test for continuous variables and Fisher's exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. p-values <0.005 were considered significant. RESULTS: The median age was similar in AR and control groups (37.4±6.23 vs. 37.3±6.27 p=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was <3 in 71.7% of patients and ≥3 in 28.3%. Disease activity measured by DAS28 was 2.89± 1.54. The age-adjusted mean serum concentration of AMH was 1.27 ng/ml [IQR 0.42; 2.24] in RA patients and 1.31 ng/ml [IQR 0.46; 3.09] in controls (p=0.608). Neither disease activity (p=0.862), nor current or previous bDMARDs treatments (p=0.871) were associated with AMH levels. However, a negative linear correlation was observed between AMH and IL-10 levels (p=0.033). CONCLUSIONS: Our study shows that ovarian reserve determined by AMH serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, AMH levels were not affected by disease activity, however, a significant correlation was observed between AMH and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have been recommended in RA pregnant patients.
31856314 Epigenetics in rheumatoid arthritis; fibroblast-like synoviocytes as an emerging paradigm 2020 Mar Rheumatoid arthritis (RA) is characterized by immune dysfunctions and chronic inflammation that mainly affects diarthrodial joints. Genetics has long been surveyed in searching for the etiopathogenesis of the disease and partially clarified the conundrums within this context. Epigenetic alterations, such as DNA methylation, histone modifications, and noncoding RNAs, which have been considered to be involved in RA pathogenesis, likely explain the nongenetic risk factors. Epigenetic modifications may influence RA through fibroblast-like synoviocytes (FLSs). It has been shown that FLSs play an essential role in the onset and exacerbation of RA, and therefore, they may illustrate some aspects of RA pathogenesis. These cells exhibit a unique DNA methylation profile in the early stage of the disease that changes with disease progression. Histone acetylation profile in RA FLSs is disrupted through the imbalance of histone acetyltransferases and histone deacetylase activity. Furthermore, dysregulation of microRNAs (miRNAs) is immense. Most of these miRNAs have shown an aberrant expression in FLSs that are involved in proliferation and cytokine production. Besides, dysregulation of long noncoding RNAs in FLSs has been revealed and attributed to RA pathogenesis. Further investigations are needed to get a better view of epigenetic alterations and their interactions. We also discuss the role of these epigenetic alterations in RA pathogenesis and their therapeutic potential.
31965238 Causal association between periodontitis and risk of rheumatoid arthritis and systemic lup 2020 Nov OBJECTIVE: To investigate whether periodontitis is causally associated with risk of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). METHODS: We performed two-sample Mendelian randomization (MR) analysis using the inverse variance-weighted (IVW), weighted median, and MR-Egger regression methods on publicly available summary statistics datasets using a periodontitis genome-wide association study (GWAS) as an exposure and RA and SLE GWASs on individuals of European descent as outcomes. RESULTS: We selected 7 or 20 single-nucleotide polymorphisms from a periodontitis GWAS as instrumental variables for RA or SLE. The IVW method results support a causal association between periodontitis and RA (beta = 0.168, SE = 0.080, p = 0.035) and SLE (beta = 0.0001, SE = 0.0001, p = 0.046) risk; however, the weighted median approach did not indicate a significant causal association. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the RA (intercept = -0.115, p = 0.078) or SLE results (intercept = 4.68E-05, p = 0.394); no significant causal association was found between periodontitis and RA and SLE. The MR estimates from the IVW, weighted median, and MR-Egger regression analyses were not consistent. CONCLUSION: Only the results of MR analysis by the IVW method indicated that periodontitis is likely causally associated with an increased risk of RA and SLE incidence. Our MR showed weak causal association between periodontitis and RA or SLE. These findings may assist in elucidating the underlying mechanisms of the effects of periodontitis on RA and SLE incidence.
32812250 Medicinal plants used against various inflammatory biomarkers for the management of rheuma 2020 Oct OBJECTIVES: Rheumatoid arthritis is a chronic autoimmune disease manifested clinically by polyarthralgia associated with joint dysfunction triggering the antibodies targeting against the self-neoepitopes determined by autoimmune responses associated with chronic arthritic attacks. The activation of macrophages and other defence cells in response to self-epitopes as biomarkers in RA provides a better understanding of pathogenesis of disease and has led to the development of novel therapeutic approaches acting as potent inhibitors of these cells. KEY FINDINGS: The current review retrieved the various medicinal plants possessing an active phytoconstituents with anti-inflammatory and antioxidant properties, which tends to be effective alternative approach over the synthetic drugs concerned with high toxic effects. The current available literature provided an evident data concluding that the active constituents like fatty acids, flavonoids, terpenes and sesquiterpene lactones attenuate the RA symptoms by targeting the inflammatory biomarkers involved in the pathogenesis of RA. SUMMARY: Despite the various synthetic treatment approaches targeting immune cells, cytokines improved the quality of life but still the drug management is challenging due to toxic and chronic teratogenic effects with anti-arthritic drugs. The current review has elaborated the selected traditionally used herbal medicinal plants with phytoconstituents possessing anti-inflammatory activity by suppressing the inflammatory biomarkers with lesser side effects and providing the future exploration of natural drug therapy for rheumatoid arthritis.
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.
31935319 The use of biological disease-modifying antirheumatic drugs for inflammatory arthritis in 2020 Jan Biological disease-modifying antirheumatic drugs (bDMARDs) are highly effective agents for the treatment of inf lammatory arthritis; however, they also possess a potential risk for serious infection. Recently, with the rapid expansion of the bDMARDs market in Korea, reports of serious adverse events related to the agents have also increased, necessitating guidance for the use of bDMARDs. Current work entitled, "Expert consensus for the use of bDMARDs drugs for inflammatory arthritis in Korea," is the first to describe the appropriate use of bDMARDs in the management of inflammatory arthritis in Korea, with an aim to provide guidance for the local medical community to improve the quality of clinical care. Twelve consensus statements regarding the use of bDMARDs for the management of rheumatoid arthritis and ankylosing spondylitis were generated. In this review, we provide detailed guidance on bDMARDs use based on expert consensus, including who should prescribe, the role of education, indications for use, and monitoring strategies for safety.
33538513 The Online Sharing of Instagram Images for Rheumatoid Arthritis. 2020 Jul 24 Social media use related to chronic disease has become pervasive, yet little research has been done to examine how social media is currently used by healthcare consumers or how to best use various social media platforms to improve health outcomes. The purpose of this study was to gain an understanding of Instagram use for image sharing related to #rheumatoidarthritis. A visual ethnography approach using content analysis was completed. Images for analysis (n = 106) were randomly selected, using the Instagram public search feature, during seven distinct periods. Content analysis, conducted by two coders, was used to identify categories and provide a sentiment analysis of the images. Approximately 75% of the images were determined to be positive by both coders. Social interaction and self-expression were the most frequently identified categories, suggesting that individuals use Instagram primarily for sharing awareness, sharing encouragement, and self-expression regarding rheumatoid arthritis. This finding is consistent with the use of Instagram for social networking and self-promotion. This study reveals new insights about how Instagram serves as a social, personal, and health-related information sharing platform particularly for those who may be socially isolated due to rheumatoid arthritis.
33183344 Fluctuation in anti-cyclic citrullinated protein antibody level predicts relapse from remi 2020 Nov 12 BACKGROUND: The positivity of anti-citrullinated protein/peptide antibodies (ACPAs) is a clinically useful diagnostic and prognostic marker in rheumatoid arthritis (RA). However, the significance of ACPA titer and its fluctuation remain unclear. This study aimed to assess the role of ACPA titer and its fluctuation on disease activity and the prognosis of RA. METHODS: Data obtained from the Kyoto University Rheumatoid Arthritis Management Alliance (KURAMA) cohort was analyzed. Patients whose ACPA was measured at least twice between 2011 and 2019 and whose ACPA was positive at least once were included in this study. The association between the clinical variable and ACPA titer or its change was investigated. RESULTS: ACPA titer was measured in a total of 3286 patients, 1806 of whom were ACPA-positive at least once. Among them, the ACPA titer level was measured more than once in 1355 patients. Very weak correlation was observed between the ACPA titer level and disease activity. Additionally, there was no trend in the fluctuation of ACPA titer level in each patient; ACPA titer level fluctuated in some patients, but not in others. Patients with high variable levels of ACPA titer were more likely to relapse from remission. In the analysis of two consecutive ACPA measurements, the titer changes predicted the relapse from remission within a year of the second measurement. CONCLUSIONS: The ACPA titer level fluctuated in some patients. Very weak correlation was observed between the ACPA titer level and disease activity. Fluctuation in ACPA titer level predicted relapse from remission in patients with RA.
32828065 Comprehensive analysis of multiple cytokines and blood parameters for the diagnosis of bac 2020 Dec Patients with rheumatoid arthritis (RA) are more susceptible to infections, which elevate the levels of relative cytokines. However, the ability of the cytokines levels to predicate bacterial infections in RA patients remains unclear. Here, we assessed the ability of the combination of serum cytokine levels and blood parameters to diagnose bacterial infections in RA patients. We measured the levels of a panel of serum cytokine and blood parameters in 168 RA patients and 81 healthy individuals. RA patients were divided into the bacterial infection (INFE) group (n = 76) and RA flare without INFE group (n = 92). Bacterial infection was confirmed by microbial culture, imaging, antibiotic response, and typical clinical symptoms. The discriminative ability of the combination of the cytokine levels and inflammatory parameters was assessed using the receiver-operating characteristic (ROC) curves analysis and a novel bioscore system. The levels of interleukin (IL)-6 (p = 0.006), IL-10 (p = 0.019), interferon (IFN)-γ (p = 0.033), CRP (p < 0.001), and ESR (p < 0.001) were higher in patients of the INFE group than in patients with RA flare, and the absolute numbers of CD19(+) B cells (p < 0.001) and CD4(+) T cells (p = 0.009) were lower. For discriminating bacterial infection, the combination of IL-6, IL-10, IFN-γ, ESR, CRP, CD19(+) B cells, and CD4(+) T cells, provided an area under the curve (AUC) of 0.827 [(95% confidence interval (CI): 0.760-0.881)], which was profoundly larger than that of IL-6, IL-10, IFN-γ, ESR, CRP, CD19(+) B cells, or CD4(+) T cells alone. In addition, we also developed a bioscore system based on the combination of these seven biomarkers. Seventeen (100%) patients with a bioscore of 0 were non-infected, while seven (100%) patients with a score of 7 had bacterial infections. The bioscore based on the combination of ESR, CRP, IL-6, IL-10, IFN-γ, CD19(+) B cells and CD4(+) T cells may be a promising and robust tool to diagnose bacterial infections in RA patients.
33287382 A Novel Pool of Microparticle Cholesterol Is Elevated in Rheumatoid Arthritis but Not in S 2020 Dec 3 Microparticles are sub-micron, membrane-bound particles released from virtually all cells and which are present in the circulation. In several autoimmune disorders their amount and composition in the circulation is altered. Microparticle surface protein expression has been explored as a differentiating tool in autoimmune disorders where the clinical pictures can overlap. Here, we examine the utility of a novel lipid-based marker-microparticle cholesterol, present in all microparticles regardless of cellular origin-to distinguish between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We first isolated a series of microparticle containing lipoprotein deficient fractions from patient and control plasma. There were no significant differences in the size, structure or protein content of microparticles isolated from each group. Compared to controls, both patient groups contained significantly greater amounts of platelet and endothelial cell-derived microparticles. The cholesterol content of microparticle fractions isolated from RA patients was significantly greater than those from either SLE patients or healthy controls. Our data indicate that circulating non-lipoprotein microparticle cholesterol, which may account for 1-2% of measured cholesterol in patient samples, may represent a novel differentiator of disease, which is independent of cellular origin.
32385761 Rheumatoid arthritis and osteoarthritis clinical practice guidelines provide few complemen 2020 Oct Sixty percent of patients with arthritis have used complementary and alternative medicine (CAM) therapies at least once. The two most common types of arthritis include rheumatoid arthritis (RA) and osteoarthritis (OA). The quality and quantity of CAM recommendations for RA and OA is currently unknown. The purpose of this research was to identify the quantity and assess the quality of CAM recommendations in clinical practice guidelines (CPGs) for the treatment and/or management of RA and OA. A systematic review was conducted to identify CPGs; MEDLINE, EMBASE and CINAHL were searched from 2008 to 2018. The Guidelines International Network and the National Center for Complementary and Integrative Health websites were also searched. Three independent reviewers evaluated the quality of reporting for each guideline that provided CAM recommendations, and the specific section providing CAM recommendations, using the AGREE II instrument. From 525 unique search results, seven guidelines (3 OA, 4 RA) mentioned CAM and 5 guidelines made CAM recommendations. Scaled domain percentages from highest to lowest were (overall, CAM) as follows: clarity of presentation (92.2% vs. 94.1%), scope and purpose (90.1% vs. 87.4%), rigour of development (72.6% vs. 64.2%), stakeholder involvement (64.8% vs. 49.6%), editorial independence (61.1% vs. 60.6%), and applicability (51.4% vs. 33.3%). None of the 5 guidelines was recommended by both appraisers for either the overall guideline or CAM section. For the overall guideline, appraisers agreed in their overall recommendation for 3 of 5 guidelines, including 3 Yes with modifications; of the remaining 2 guidelines, 1 was rated by the three appraisers as 1 No and 2 Yes with modifications, while 1 guideline was rated at 2 Yes and 1 Yes with modifications. For the CAM section, appraisers agreed in their overall recommendation for all 5 guidelines including 1 No, and 4 Yes with modifications. Roughly half of arthritis CPGs found included in this review provided CAM recommendations. The quality of CAM recommendations are of lower quality than overall recommendations across the scope and purpose, stakeholder involvement, rigour of development, applicability, and editorial independence domains. Quality varied within and across guidelines.
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.
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.