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ID PMID Title PublicationDate abstract
31526517 Trends of Cardiac Complications in Patients With Rheumatoid Arthritis: Analysis of the Uni 2021 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory condition. Chronic inflammation is associated with atherosclerosis, hypertension, diabetes, chronic obstructive pulmonary disease (COPD), chronic kidney disease. But sparse data are available regarding the trends of cardiovascular diseases and complications in RA. We conducted a National Inpatient Sample database analysis to demonstrate the trends of cardiac complications in patients with RA. METHODS: We used National Inpatient Sample data from 2005 to 2014 to identify admissions with the diagnosis of RA and identified who had associated cardiovascular complications also. The International Classification of Diseases-9th Revision-Clinical Modification codes were used for the diagnoses of RA; congestive heart failure (CHF), acute myocardial infarction (AMI), and atrial fibrillation (AF). RESULTS: A statistically significant increasing trend of AMI, CHF, and AF was found. Independent predictors of mortality in RA patients with AMI were age (OR 1.03, CI 1.02-1.04; P < 0.001), COPD (OR 1.67, CI 1.40-2.00; P < 0.001), cerebrovascular disease (OR 2.207, CI 1.71-2.86; P < 0.001), renal disease (OR 1.42, CI 1.16-1.75; P = 0.001), and alcohol abuse (OR 2.73, CI 1.73-4.32; P < 0.001). Independent predictors of mortality in RA patients with CHF were age (odds ratio [OR] 1.02, confidence interval [CI] 1.017-1.024; P < 0.001]), COPD (OR 1.09, CI 1.01-1.18; P = 0.023), cerebrovascular disease (OR 1.67, CI 1.44-1.95; P < 0.001), renal disease (OR 1.16, CI 1.07-1.27; P = 0.001). Independent predictors of mortality in RA patients with AF were age (OR 1.02, CI 1.02-1.03; P < 0.001), race (OR 1.16, CI 1.02-1.31; P = 0.022), COPD (OR 1.56, CI 1.42-1.71; P < 0.001), peripheral arterial disease (OR 1.34, CI 1.16-1.53; P < 0.001), cerebrovascular disease (OR 2.27, CI 1.0-2.58; P < 0.001), renal disease (OR 1.60, CI 1.44-1.80; P < 0.001). The mortality trend has increased significantly in the CHF (P = 0.025) and AF (P = 0.042) groups during this study period. CONCLUSIONS: We have found a significant increase in trend of cardiovascular complications in RA patients. The proportion of patients, with cardiovascular comorbidities, have also been increased significantly.
33433729 Disease-modifying drug retention rate according to patient age in patients with early rheu 2021 May Physicians are sometimes hesitant to use disease-modifying antirheumatic drugs (DMARDs) in elderly patients with rheumatoid arthritis (RA), as they are deemed too fragile, although there are no sufficient scientific evidence. We aimed to compare DMARD treatment retention in early RA patients from the ESPOIR cohort, according to age upon inclusion. Overall, treatment retention was evaluated as the percentage of patients whose DMARDs were not stopped, with stratification by age group: < 50, 50-64, and > 65 years. Survival curves were measured using the Kaplan-Meier method. Of the entire ESPOIR cohort (n = 813), 7% were > 65 years old. Methotrexate (MTX) was used by 521 patients, and was the sole DMARD for 198 patients. MTX treatment retention appeared better in patients > 65 years old compared to < 50 years old [HR 0.45 (0.25; 0.81); p = 0.008, n = 195/198] with adjustment on sex, smoking, positive anti-cyclic citrullinated peptide antibodies, positive rheumatoid factor, body mass index, changes in DAS28 and corticosteroid treatment. The proportion of patients using etanercept (n = 111), and this drug's retention rate, did not differ according to patient age. The proportion of patients treated with adalimumab (n = 104) was significantly higher in patients < 50 years old (p = 0.003), and treatment retention was marginally better among younger patients [HR 1.68 (0.88; 3.22), p = 0.12]. Within the ESPOIR cohort, DMARD retention did not appear to differ according to age-except for better retention of MTX treatment in patients 50-64 years old, and of adalimumab in patients < 50 years old.
33437990 Rare immunofluorescence patterns of autoantibodies on HEp-2 cells defined by ICAP identify 2021 Aug 2 OBJECTIVES: ANA are the most extensively used test for the diagnosis of systemic autoimmune diseases. However, testing by indirect immunofluorescence assays (IIFAs) on HEp-2 cells, the gold standard test, is time-consuming and needs expertise. Thus there is a trend to replace it with other automated solid-phase assays directed against specific ANA. Nonetheless, the Hep-2 cell is an autoantigen array and ANA have been classified into 29 types, some of them with no clear association with a specificity to be detected. It is especially in these uncommon patterns where no clinical relationship is found and no antigenic specificity is detected. Here we retrospectively collected clinical data from patients with confirmed uncommon HEp-2 IIFA patterns to search for an associated clinical condition. METHODS: We conducted an observational retrospective study including 608 patients with organ-specific and non-organ-specific autoimmune diseases (OSADs and NOSADs, respectively) with a confirmed rare pattern of ANA detected by IIFA on HEp-2 cells in the routine practice of the Spanish European Autoantibodies Standardization Initiative laboratories. Inclusion criteria are the existence of a minimum follow-up of 2 years and the availability of clinical data. RESULTS: Nuclear patterns were more frequent in SLE (P = 0.001) and SS (P = 0.001), whereas the cytoplasmic ones were significantly higher in SSc (P = 0.022) and inflammatory myositis (P = 0.016). Mitotic patterns did not show any preferences for a specific disease and 62.7% of them corresponded to the nuclear mitotic apparatus pattern (AC-26). The most frequent NOSADs in patients with the AC-26 pattern were SLE (28.6%), SS (11.9%) and RA (11.9%). The cytoplasmic HEp-2 IIFA patterns were equally distributed in both groups of patients. In the OSAD patients there was no predominant pattern, except for AC-6 in primary biliary cholangitis due to Sp-100 antibodies (P < 0.001). CONCLUSION: Detection of infrequent ANA might be a unique finding with no disease-associated specificities and could lead to the suspicion of an autoimmune disease.
33026713 Addressing Health Literacy Needs in Rheumatology: Which Patient Health Literacy Profiles N 2021 Jan OBJECTIVE: To identify and describe health literacy profiles of patients with rheumatic diseases and explore whether the identified health literacy profiles can be generalized to a broader rheumatology context. METHODS: Patients with rheumatoid arthritis, spondyloarthritis, and gout from 3 hospitals in different regions in The Netherlands completed the Health Literacy Questionnaire (HLQ). Hierarchical cluster analysis was used to identify patients' health literacy profiles based on 9 HLQ domains. A multinomial regression model with the identified health literacy profiles as the dependent variable was fitted to assess whether patients with a given disease type or attending a given hospital were more likely to belong to a specific profile. RESULTS: Among 895 participating patients, the lowest mean HLQ domain scores (indicating most difficulty) were found for "critical appraisal," "navigating the health system," and "finding good health information." The 10 identified profiles revealed substantial diversity in combinations of strengths and weaknesses. While 42% of patients scored moderate to high on all 9 domains (profiles 1 and 3), another 42% of patients (profiles 2, 4, 5, and 6) clearly struggled with 1 or several aspects of health literacy. Notably, 16% (profiles 7-10) exhibited difficulty across a majority of health literacy domains. The probability of belonging to one of the profiles was independent of the hospital where the patient was treated or the type of rheumatic disease. CONCLUSION: Ten distinct health literacy profiles were identified among patients with rheumatic diseases, independent of disease type and treating hospital. These profiles can be used to facilitate the development of health literacy interventions in rheumatology.
31651103 Finger Joint Cartilage Evaluated by Semiquantitative Ultrasound Score in Patients With Rhe 2021 Feb OBJECTIVE: Joint destruction in rheumatoid arthritis (RA) includes both bone and cartilage lesions. Since joint space narrowing (JSN) is not a direct evaluation of cartilage using radiography, we aimed to examine the validity of ultrasound (US) cartilage evaluation using a semiquantitative method in patients with RA. METHODS: We enrolled 103 patients with RA who were in remission or showing low disease activity and 42 healthy subjects. The cartilage thickness of the bilateral metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the second to fifth fingers was measured by US, and the recorded images were scored semiquantitatively using a scale of 0-2. In addition, the JSN of the corresponding joints was scored using a hand radiograph. The relationships between total cartilage thickness, its semiquantitative score, and JSN score were assessed using Spearman's rank correlation coefficients. RESULTS: Total cartilage thickness was significantly thinner in patients with RA compared to healthy subjects for both the MCP and PIP joints (both P < 0.001). The semiquantitative sum of 16 joints ranged from 2 to 26 (median 8) in patients with RA, which was significantly greater than the 0-11 (median 4) in healthy subjects (P < 0.001). In patients with RA, the semiquantitative score showed a significant negative correlation with cartilage thickness (ρ = -0.64, P < 0.001) and a significant positive correlation with JSN score (ρ = 0.66, P < 0.001). Furthermore, these scores showed a significant correlation with RA disease duration. CONCLUSION: A simplified and direct evaluation of finger joint cartilage damage by semiquantitative US score is valid and useful for patients with RA.
34504395 The Biological Disease-Modifying Antirheumatic Drugs and the Risk of Cardiovascular Events 2021 OBJECTIVE: To assess the association between the use of biological disease-modifying antirheumatic drugs (bDMARDs) and the risk of cardiovascular events in patients with systemic inflammatory conditions. METHODS: Eligible cohort studies or randomized controlled trials (RCTs) from inception to January 2021 were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for cardiovascular outcomes were calculated in the fixed- and random-effects model accordingly. Associated factors with risks of cardiovascular events were also studied in sensitivity analyses and metaregression analyses. RESULTS: Compared with non-bDMARD users, the risks of myocardial infarction (MI) (OR = 0.74, 95% CI, 0.63 to 0.87), heart failure (OR = 0.84, 95% CI, 0.74 to 0.95), cardiovascular (CV) death (OR = 0.62, 95% CI, 0.40 to 0.95), all-cause mortality (OR = 0.64, 95% CI, 0.58 to 0.70), and 3P-MACE (composite endpoint of MI, stroke, and CV death) (OR = 0.69, 95% CI, 0.53 to 0.89) were significantly reduced in bDMARD users, which were mainly driven by the risk reduction in patients with rheumatoid arthritis (RA). TNF-α inhibitors exhibited consistent benefits in reducing the risks of MI, heart failure, CV death, all-cause mortality, and 3P-MACE. Moreover, the risks of heart failure, CV death, all-cause mortality, and 3P-MACE were significantly reduced in bDMARD users with follow-up over one year. CONCLUSIONS: The use of bDMARDs might be associated with the reduced risks of CV events, especially in patients with RA. The CV events might be less frequent in bDMARD users with TNF-α inhibitors or follow-up over one year. More investigations are needed to validate conclusions.
33280072 Analysis of a single-institution cohort of patients with Felty's syndrome and T-cell large 2021 Jan T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown.Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 10(9)/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated.Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 10(9)/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5(-/dim) on CD3(+)CD8(+) T-lymphocytes was observed in both RA-associated T-LGLL and FS.STAT3 gene mutations or LGL counts over 2 × 10(9)/L in RA patients are indicative of T-LGLL.
34112702 Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumat 2021 Jun OBJECTIVES: Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood. METHODS: 15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment. RESULTS: Disease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders. CONCLUSIONS: TCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.
34414960 Incidence of venous thromboembolism in rheumatoid arthritis, results from a "real-life" co 2021 Aug 20 Rheumatoid arthritis (RA) is associated with an increased risk of venous thromboembolism (VTE) occurrence. In this work, we assessed the incidence and predictive factors of VTE in our "real-life" cohort of RA patients. To contextualize our results, we reviewed the available literature about this topic.We performed a retrospective analysis of prospectively followed-up patients with RA attending our Rheumatologic Clinic between January 2010 and December 2020. Each patient was investigated for VTE occurrence. Incident cases were reported as incidence proportion and incidence rate per 1000 person-years at risk. Possible predictive factors were also exploited by regression analyses. Available literature about this topic was also assessed.In this evaluation, 347 consecutive patients without previous evidence of VTE, attending our Rheumatologic Clinic from 2010 to 2020, were studied. In our "real-life" cohort, the incidence proportion of VTE was 3.7% (2.7-4.7%) and considering over 1654 person-years, an incidence rate of 7.8 × 1000 (2.5-11.7). Exploratively assessing predictive factors in our cohort, older age (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01-1.14, p = .015), higher body mass index (HR 1.37, 95% CI 1.04-1.80, P = .026), and longer disease duration (HR 1.11, 95% CI 1.03-1.20, P = .006) resulted to be significant predictors of VTE occurrence during the follow-up.In our "real-life" cohort, VTE burden has been suggested in patients with RA. Comparing our results with previous data derived from randomized controlled trials and administrative data, some different findings were retrieved about incidence of VTE. Assessing predictive factors, older age, higher body mass index, and longer disease duration resulted to be significant predictors of VTE occurrence during the follow-up. Taking together these observations, a further evaluation of this issue on specific designed studies is needed to provide more generalizable results to the daily clinical practice.
33427511 Expression of extracellular matrix components and cytokine receptors in human fibrocytes d 2021 Nov Purpose: Fibroblast-like synoviocytes (FLS) represent one of the principal effectors of joint damage in rheumatoid arthritis (RA). Recent discovery of the circulating fibrocyte, a potential precursor of FLS, has raised issues regarding the characterization of fibrocytes with respect to their morphology and their biological role. In this study, we evaluated the morphology of fibrocytes in vitro and their ability to produce different extracellular matrix (ECM) components in comparison with two populations of RA FLS: synovial fluid FLS (fd-FLS) and intimal lining FLS (td-FLS). We also studied the expression of ECM regulators and a set of cytokine receptors involved in the pathogenesis of RA. Materials and Methods: Fibrocytes were cultured from peripheral blood of patients with RA. FLS were cultured from synovial fluids and tissues. ECM proteins (collagen I (col I) and fibronectin), Matrix metalloproteinases (MMP) (MMP3, and MMP9), ECM regulators (β catenin, TCF4, and c-fos), and cytokine receptors (CXCR1, CXCR2, CXCR3, IL1RI, IL1RII, and IL6Rα) were analyzed using qRT-PCR and/or western blot. Results: Our results demonstrated that fibronectin and MMP3 levels were higher in FLS compared to fibrocytes. Although MMP9 was expressed in the three cell types, its level was greater in fibrocytes than in td/fd FLS. The three cell types expressed CXCR3, IL1RI, IL1RII, and IL6Rα, while the expression of CXCR1 and CXCR2 was restricted to fibrocytes. Conclusion: Our results demonstrated that fibrocytes express ECM molecules and cytokines receptors. The observed differences between fibrocytes and FLS may be due to their distinct functions or differentiation state during RA.Abbreviations: RA: Rheumatoid ArthritisFLS: fibroblast-like synoviocytestd: tissue derivedfd: fluid derivedSF: Synovial FluidWnt: WinglessMMP: Matrix MetalloproteinaseCIA: murine collagen induced arthritisECM: Extracellular matrixcol I: Collagen ITCF/LEF: T-cell factor/lymphoid enhancer-binding factorAP1: Activator Protein 1.
33443386 Rheumatoid Arthritis Versus Osteoarthritis in Patients Receiving Revision Total Knee Arthr 2021 Dec 1 BACKGROUND: The impacts of rheumatoid arthritis (RA) on perioperative risks among patients undergoing revision total knee arthroplasty (rTKA) have not been investigated yet. Thus, we hypothesized that patients with RA sustained increased perioperative risks and higher resource consumption burdens as compared to patients with osteoarthritis (OA) during the perioperative period. PATIENTS AND METHODS: The National Inpatient Sample (NIS) database was used to compare the demographic characteristics, major in-hospital complications, resource consumptions, and in-hospitalization mortality between patients with RA and OA after rTKA. A 1:1 propensity score-matching, χ2 test, independence-sample T-test, and logistic regression analysis were done in statistical analyses to answer our hypotheses. RESULTS: 4.3% (6363/132,405) of rTKA patients were diagnosed with RA. They tended to be women and received revision for infection but with similar ages as compared to patients with OA. Except for acute postoperative anemia (odds ratio [OR] = 1.196), blood transfusion (OR = 1.179), prolonged hospitalization (OR = 1.049), and higher total cost (OR = 1.145), patients with RA sustained decreased odds of acute renal failure (OR = 0.804) and urinary complications (OR = 0.467). Besides, the other observed in-hospital complications showed no differences between patients with RA and OA. CONCLUSION: Despite consuming greater in-hospital resources, patients with RA did not suffer increased odds of most in-hospital complications and in-hospital mortality for a revision TKA during the perioperative period. Compared with patients with OA, patients with RA sustained equivalent perioperative risks in the United States between 2002 and 2014.
34893669 Epigenome association study for DNA methylation biomarkers in buccal and monocyte cells fo 2021 Dec 10 Genetics (i.e., mutations) has been assumed to be the major factor in rheumatoid arthritis (RA) etiology, but accounts for a minority of the variance in disease risk for RA. In contrast to genetics, the environment can have dramatic impacts on epigenetics that associate with disease etiology. The current study used buccal cells and purified blood monocytes from two different clinical cohorts involving Caucasian or African American female populations with or without arthritis. The differential DNA methylation regions (DMRs) between the control and RA populations were identified with an epigenome-wide association study. The DMRs (i.e., epimutations) identified in the buccal cells and monocytes were found to be distinct. The DMR associated genes were identified and many have previously been shown to be associated with arthritis. Observations demonstrate DNA methylation epimutation RA biomarkers are cell type specific and similar findings were observed with the two racial background populations. Rheumatoid arthritis susceptibility epigenetic diagnosis appears feasible and may improve the clinical management of RA and allowpreventative medicine considerations.
34725638 Efficacy and Safety of Qiwei Tongbi Oral Liquid in Patients with Stable Long-Standing Rheu 2021 OBJECTIVE: Our study is aimed at investigating the efficacy and safety of Qiwei Tongbi oral liquid in patients with stable long-standing rheumatoid arthritis (RA). METHOD: 140 patients with stable long-standing RA were recruited into the Qiwei Tongbi oral liquid group or the control group. At study recruitment and after 12 weeks of treatment, their C-reactive protein (CRP) levels, interleukin-6 (IL-6) levels, erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ), visual analogue scale (VAS), and Disease Activity Score (DAS) 28 were compared in two groups. RESULTS: Patients in the Qiwei Tongbi oral liquid group had a lower level of CRP, IL-6, VAS scale, and HAQ score compared to patients in the control group (CRP: 3.51 ± 1.57 vs.5.47 ± 1.72 mg/L, P < 0.001; IL-6: 1.62 ± 0.8 vs. 2.19 ± 0.88 pg/mL, P < 0.001; VAS scale: 1.59 ± 0.69 vs. 2.66 ± 1.02, P < 0.001; and HAQ score: 1.19 ± 0.46 vs. 1.41 ± 0.50, P = 0.005). The ESR and DAS28 did not reach statistical difference. No damage to liver and kidney functions was observed in both groups. CONCLUSION: Qiwei Tongbi oral liquid has the tendency to decrease the inflammation levels and pain score and improve patients' outcomes in patients with stable long-standing RA.
33030631 A multimodal intervention increases influenza vaccine uptake in rheumatoid arthritis. 2021 Feb Annual influenza vaccination is recommended for patients with rheumatoid arthritis (RA), but coverage is suboptimal. We assessed the impact of an implementation strategy in enhancing vaccination uptake in RA. We evaluated a multimodal implementation strategy at rheumatology clinics that included 3 approaches: patient recalls, a nurse providing vaccines, and physician reminders. We compared patient-reported vaccination rates after implementation with those reported before the implementation strategy in a nonequivalent control group. In multivariate analyses, we assessed factors potentially associated with influenza vaccine uptake. One hundred and sixteen RA patients were vaccinated during the intervention. The influenza vaccination rate in RA increased from 48.5% (65/136) before implementation to 62.6% (67/107) after implementation (difference of 14.1, 95% CI 1.5, 26.1). In multivariate analyses, older age, biologics use, and physician recommendation for vaccination were associated with influenza vaccine uptake. A multimodal intervention was associated with increased influenza vaccine coverage among RA patients. Older patients and those on biologics were more likely to be immunized against influenza. Physician's recommendations are important to promote vaccine coverage. Key Points • Despite current recommendations, influenza vaccine uptake among rheumatoid arthritis (RA) patients is suboptimal. • A multimodal implementation strategy facilitating access to influenza vaccine and raising awareness through vaccination reminders improved immunization uptake in RA. • Physicians play a key role in promoting annual seasonal influenza vaccination. • The reasons for vaccine hesitancy in RA should be addressed to reach a vaccination target of 80% required to reduce the burden of this preventable infection.
34842006 IL-21 impairs pro-inflammatory activity of M1-like macrophages exerting anti-inflammatory 2022 Mar Objective：Macrophages are the main source of inflammatory mediators and play important roles in the pathogenesis of rheumatoid arthritis (RA). Interleukin-21 (IL-21) regulates both innate and adaptive immune responses and exerts major effects on inflammatory responses that promote the development of RA. However, its effect on macrophage polarisation remains unclear.Methods：CD14(+) monocytes of the peripheral blood of Human healthy donors (HD) and RA, and macrophages of RA synovial fluid (RA-SF MΦs) were isolated. IL-21 receptor (IL-21R) was detected by flow cytometry. Cytokine production by MΦs from different sources pre-treated with IL-21 and/or LPS was measured by real-time polymerase chain reaction (RT-PCR) and ELISA. CD14(+) monocytes were differentiated into M1-like and M2-like macrophages via stimulation with GM-CSF, interferon-γ (IFN-γ), and LPS or M-CSF, IL-4, and IL-13, respectively. To determine the effect of IL-21 on macrophage polarisation, macrophage phenotypes, gene expression, and cytokine secretion were detected by flow cytometry, RT-PCR, and ELISA. TLR4 and ERK1/2 were determined by western blotting.Results：IL-21 exerted different effects on LPS-mediated inflammatory responses in various derived MΦs, and inhibited macrophages polarisation to M1-like macrophages and promote their polarisation to M2-like macrophages in HD and RA. Moreover, IL-21 inhibited LPS-mediated secretion of inflammatory cytokines, probably by downregulating the ERK1/2, in RA-SF MΦs.Conclusion：For the first time, we indicated that IL-21 inhibits LPS-mediated cytokine production in RA-SF MΦs, and impairs pro-inflammatory activity of M1-like macrophages, hereby exerting anti-inflammatory effects on RA. Thus, IL-21 might not be an appropriate therapeutic target for RA.
32782226 Total ankle arthroplasty and ankle arthrodesis in rheumatic disease patients: An analysis 2021 Apr INTRODUCTION: Rheumatoid arthritis (RA), can manifest as an inflammatory arthropathy in the ankle. As a result, this study sought to examine the role of RA with respect to complications in patients undergoing either total ankle arthroplasty or ankle arthrodesis by utilizing the National Inpatient Sample to assess for correlations. METHODS: Admissions for TAA and AA were extracted from the National Inpatient Sample using primary ICD-9-CM diagnosis codes. Patients aged 18-65 years with a duration of hospital stay of >3 days and isolated complications were included. Multivariable regression was then performed within matched groups to determine differences. RESULTS: There was decreased risk of myocardial infarction, pulmonary embolism, surgical site infection, and urinary tract infection in patients with RA. Postoperative development of pneumonia was seen at a higher rate in patients with RA. CONCLUSION: RA is not associated with a markedly increased complication burden in the appropriately chosen surgical candidate for ankle arthrodesis and ankle arthroplasty.
34494214 Association of interleukin-6 promoter polymorphism with rheumatoid arthritis: a meta-analy 2022 Feb OBJECTIVES: The association of interleukin-6 (IL-6) -174G/C (rs1800795) and IL-6 -572G/C (rs1800796) single-nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) was inconsistent among previous studies. This paper aims to investigate the association between IL-6 promoter polymorphism with RA in different ethnics. METHODS: Relevant studies were searched using Medline and Google Search engines; STATA software was used to perform the meta-analysis. Pooled odds ratios (OR) were calculated to estimate the potential genetic associations. Subgroup analysis and sensitivity analysis were applied to explore the sources of heterogeneity. Lastly, we used TSA (trial sequential analysis) software to verify the reliability of meta-analysis results. RESULTS: A total of 18 studies were included, involving 8116 subjects (3820 RA patients and 4296 controls). We found a tendency to associate RA with the IL-6 -174G/C allele in Asians (C vs G: OR = 4.56, 95% CI = 1.85-11.23; P < 0.001); with IL-6 -572G/C genotype or allele frequencies, there was no statistical differences between RA patients and controls (P > 0.05). TSA results indicate that the current meta-analysis can draw conclusions. CONCLUSIONS: IL-6-174G/C gene polymorphism were associated with increased risk of RA in Asians, but not in Caucasians. There was no association between IL-6 -572G/C gene polymorphism and the risk of RA. Key Points • Although the association between interleukin-6 (IL-6) promoter polymorphism and rheumatic arthritis (RA) has been discussed in the previous meta-analysis, their conclusions are inconsistent. • In this study, trial sequential analysis (TSA) was introduced into the meta-analysis, and the following two important conclusions were confirmed: (1) IL-6-174G/C gene polymorphism was associated with increased risk of RA in Asians, but not in Caucasians. (2) There was no association between IL-6 -572G/C gene polymorphism and the risk of RA.
33403456 Investigation of Alpinia calcarata constituent interactions with molecular targets of rheu 2021 Jan 5 Rheumatoid arthritis (RA) is a systemic autoimmune disorder that commonly affects multiple joints of the body. Currently, there is no permanent cure to the disease, but it can be managed with several potent drugs that cause serious side effects on prolonged use. Traditional remedies are considered promising for the treatment of several diseases, particularly chronic conditions, because they have lower side effects compared to synthetic drugs. In folklore, the rhizome of Alpinia calcarata Roscoe (Zingiberaceae) is used as a major ingredient of herbal formulations to treat RA. Phytoconstituents reported in A. calcarata rhizomes are diterpenoids, sesquiterpenoid, flavonoids, phytosterol, and volatile oils. The present study is intended to understand the molecular-level interaction of phytoconstituents present in A. calcarata rhizomes with RA molecular targets using computational approaches. A total of 30 phytoconstituents reported from the plant were used to carry out docking with 36 known targets of RA. Based on the docking results, 4 flavonoids were found to be strongly interacting with the RA targets. Further, molecular dynamics simulation confirmed stable interaction of quercetin with 6 targets (JAK3, SYK, MMP2, TLR8, IRAK1, and JAK1), galangin with 2 targets (IRAK1 and JAK1), and kaempferol (IRAK1) with one target of RA. Moreover, the presence of these three flavonoids was confirmed in the A. calcarata rhizome extract using LC-MS analysis. The computational study suggests that flavonoids present in A. calcarata rhizome may be responsible for RA modulatory activity. Particularly, quercetin and galangin could be potential development candidates for the treatment of RA. Investigation of Alpinia calcarata constituent interactions with molecular targets of rheumatoid arthritis: docking, molecular dynamics, and network approach.
34715910 Immunoprofiling of early, untreated rheumatoid arthritis using mass cytometry reveals an a 2021 Oct 29 BACKGROUND: Autoantibody production is a hallmark of rheumatoid arthritis (RA). Anti-citrullinated protein antibodies (ACPA) are highly disease-specific, and their presence is associated with more severe disease and poor prognosis compared to ACPA-negative patients. However, the immune cell composition associated with antibody-positive/negative disease is incompletely defined. Mass cytometry (MC) is a high-dimensional technique offering new possibilities in the determination of the immune cell composition in rheumatic diseases. Here, we set up a broad phenotyping panel to study the immune cell profile of early untreated RA to investigate if specific immune cell subsets are associated with ACPA+ versus ACPA- RA. METHODS: Freshly obtained PBMCs of early, untreated RA patients (8 ACPA+ and 7 ACPA-) were analysed using a 36-marker MC panel, including markers related to various immune lineages. Data were processed using Cytosplore for dimensional reduction (HSNE) and clustering. Groups were compared using Cytofast. A second validation cohort of cryopreserved PBMCs obtained from early RA patients (27 ACPA+ and 20 ACPA-) was used to confirm MC data by flow cytometry (FC). FC data were processed and analysed using both an unsupervised analysis pipeline and through manual gating. RESULTS: MC indicated no differences when comparing major immune lineages (i.e. monocytes, T and B cells), but highlighted two innate subsets: CD62L(+) basophils (p = 0.33) and a subset of CD16(-) NK cells (p = 0.063). Although the NK cell subset did not replicate by FC, FC replication confirmed the difference in CD62L(+) basophil frequency when comparing ACPA+ to ACPA- patients (mean 0.32% vs. 0.13%; p = 0.01). CONCLUSIONS: Although no differences in major lineages were found between early ACPA+ and ACPA- RA, this study identified the reduced presence of activated basophils in ACPA-negative disease as compared to ACPA-positive disease and thereby provides the first evidence for a connection between activated basophils and ACPA status.
34393649 The Emerging Roles of CCN3 Protein in Immune-Related Diseases. 2021 The CCN proteins are a family of extracellular matrix- (ECM-) associated proteins which currently consist of six secreted proteins (CCN1-6). CCN3 protein, also known as nephroblastoma overexpressed protein (NOV), is a member of the CCN family with multiple biological functions, implicated in major cellular processes such as cell growth, migration, and differentiation. Recently, CCN3 has emerged as a critical regulator in a variety of diseases, including immune-related diseases, including rheumatology arthritis, osteoarthritis, and systemic sclerosis. In this review, we will briefly introduce the structure and function of the CCN3 protein and summarize the roles of CCN3 in immune-related diseases, which is essential to understand the functions of the CCN3 in immune-related diseases.