Browse

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

ID PMID Title PublicationDate abstract
32450644 [Changes and clinical significance of peripheral blood CD8(+)CD25(+)T cells in rheumatoid 2020 May 26 Objective: To investigate the expression of CD8(+)CD25(+)T cells in peripheral blood of patients with rheumatoid arthritis (RA) and its correlation with clinical indicators of rheumatoid arthritis. Methods: Peripheral blood was collected from 38 patients with RA, and 20 healthy control subjects, RA patients admitted to Peking University people's hospital from May to October 2018, and record the RA patients with the clinical manifestations and laboratory indexes, extraction in the peripheral blood lymphocytes, using flow cytometry to analyse the percentage of CD8(+)CD25(+)T cells in peripheral blood, by using the software SPASS20 and Prism6 to analyze its correlation with clinical and laboratory indices. Results: The expression of CD8(+)CD25(+)T cells in peripheral blood of RA patients was significantly increased, which was statistically different from that of healthy patients (P<0.05). CD8(+)CD25(+)T cells in peripheral blood of RA patients showed significant positive correlation with ESR(r=0.352,P=0.030), CCP(r=0.312,P=0.047) and DAS28(r=0.330,P=0.043), and negatively correlated with C3 (r=-0.354,P=0.046) and C4(r=-0.440,P=0.010).No significant correlation was found in other indicators. In RA patients, there were statistically significant differences in CD8(+)CD25(+)T cells between the low-disease active group and the high-disease active group(P<0.05), but CD8(+)CD25(+)T cells between the low-disease active group and the moderate-disease active group, or between the moderate-disease active group and the high-disease active group had no significant statistical difference. Conclusion: CD8(+)CD25(+)Tcells in peripheral blood of patients with RA are significantlyincreased, and aresignificantly correlated with laboratory and clinical indicators, which may play an important role in the pathogenesis of rheumatoid arthritis.
33040022 Decline of ovarian function in patients with rheumatoid arthritis: serum anti-Müllerian h 2020 Oct OBJECTIVE: Rheumatoid arthritis (RA) often affects women in their fertile age, and is known to compromise female fertility. Serum anti-Müllerian hormone (AMH) levels are a proxy for the total number of primordial follicles, and a reliable predictor of the age at menopause. Our objective was to study the longitudinal intra-individual decline of serum AMH levels in female RA patients. METHODS: Female RA patients from a nationwide prospective cohort (2002-2008) were re-assessed in 2015-2016. Serum AMH levels were measured using the picoAMH assay and compared with healthy controls. A linear mixed model (LMM) was built to assess the effect of RA-related clinical factors on the decline of AMH levels. RESULTS: A group of 128 women were re-assessed at an age of 42.6±4.4 years, with a median disease duration of 15.8 (IQR 12.7-21.5) years. The time between first and last AMH assessments was 10.7±1.8 (range 6.4-13.7) years. Participants represented a more fertile selection of the original cohort. At follow-up, 39% of patients had AMH levels below the 10th percentile of controls (95% CI 31% to 48%), compared with 16% (95% CI 9.3% to 22%) at baseline. The LMM showed a significant decline of AMH with increasing age, but no significant effect of RA-related factors on AMH. CONCLUSION: AMH levels in RA patients showed a more pronounced decline over time than expected, supporting the idea that in chronic inflammatory conditions, reproductive function is compromised, resulting in a faster decline of ovarian function over time and probably an earlier age at menopause.
31549772 What Does the Patient Global Health Assessment in Rheumatoid Arthritis Really Tell Us? Con 2020 Nov OBJECTIVE: To estimate the contributions of health-related quality of life domains to the patient global assessment of disease activity (PtGA) in rheumatoid arthritis (RA). METHODS: Data are drawn from baseline visits of 2 observational RA cohorts. Participants completed forms for patient-reported outcome measures, including PtGA and measures from the Patient-Reported Outcomes Measurement Information System, and clinical data were collected. Factor analysis was used to identify latent variables, and multivariable linear regression was used to estimate determinants of the PtGA. RESULTS: Patients were mostly female (81%), white (78%), and had established disease (mean ± SD 12.3 ± 10.7 years), with 62% in remission or having low disease activity. In cohort 1 (n = 196), the following 2 factors emerged: 1) daily function (moderate-to-strong [i.e., >|0.65|] loadings of physical function, pain interference, social participation, and fatigue, and weak [>0.35] loadings of sleep disturbance); and 2) emotional distress (strong loadings of depression and anxiety). In crude analysis, daily function explained up to 53% and emotional distress up to 20% of the variance in PtGA. In both cohorts, in adjusted analyses, daily function and, to a much lesser extent, swollen joint count independently predicted PtGA; age was inversely related to PtGA in cohort 1 only. CONCLUSION: These findings suggest that in patients with RA, PtGA ratings largely reflect the extent to which patients feel they can function in everyday roles and are not impacted by mood. This suggests that higher than expected PtGA scores may offer an opportunity to discuss patient expectations regarding roles and activities and the impact of their RA symptoms on daily function.
32943723 Association of age with the non-achievement of clinical and functional remission in rheuma 2020 Sep 17 Patient-reported outcome (PRO) is included in the remission criteria of rheumatoid arthritis (RA). We aimed to determine the effect of age on PRO and the subsequent achievement of clinical and functional RA remission criteria. Three hundred and one patients with non-rheumatic diseases were evaluated using the 0-10 cm visual analog scale (VAS) assessment for musculoskeletal symptoms and a functional health assessment questionnaire-disability index (HAQ-DI). These assessments were compared with those obtained from 149 patients with RA with negative tender/swollen joint counts and normal serum C-reactive levels (objective clinical remission). Of the 301 patients, 32.2%, 26.6%, and 41.2% were classified as non-elderly (< 65 years), early elderly (65-74 years), and late-elderly (≥ 75 years) patients, respectively. VAS > 1 cm and HAQ-DI ≥ 0.5 were observed in 7.3% and 14.5%, respectively, in late-elderly patients, whereas ≤ 1.0% of non-elderly and early elderly patients for the both. Among 149 RA patients in objective remission, however, > 20% and > 10% of early elderly patients (and even non-elderly patients) had VAS > 1 cm and HAQ-DI ≥ 0.5, respectively, and 34.0% and 35.8% of late-elderly patients with RA had VAS > 1 cm and HAQ-DI ≥ 0.5, respectively. Multivariate logistic analysis revealed that age and RA were associated with the non-achievement of VAS ≤ 1 cm and HAQ-DI < 0.5. Therefore, the effect of age, which was independent of the presence of RA even without any objective disease activity, on PRO and the non-achievement of clinical and functional remission criteria was demonstrated.
32920323 Association of serum anti-centromere protein F antibodies with clinical response to inflix 2020 Oct BACKGROUND: One-third of rheumatoid arthritis (RA) patients demonstrate no clinical improvement after receiving tumor necrosis factor inhibitors (TNFi). The presence of serum autoantibodies is a hallmark in RA and may provide information on future response to treatment. The aim of this prospective study was to search for novel serum autoantibodies useful to predict clinical response to TNFi. METHODS: The autoantibody repertoire was profiled on RA patients treated with TNFi as a first line of biologic therapy (N = 185), who were recruited in three independent cohorts. The presence and levels of autoantibodies in serum at baseline were analysed in association with the clinical response after 24 weeks follow-up. A multiplex bead array built using antigens selected from an initial untargeted screening was employed to identify the autoantibodies on a discovery cohort (N = 50) and to verify and validate the results on verification (N = 61) and validation (N = 74) cohorts. Non-parametric tests, meta-analysis and Receiver Operating Curves (ROC) were performed in order to assess the clinical relevance of the observed findings. RESULTS: Novel autoantibodies were associated with the clinical response to TNFi, showing different reactivity profiles among the different TNFi. The baseline levels of IgG antibodies against Centromere protein F (CENPF), a protein related to cell proliferation, were significantly (p<0.05) increased in responders (N = 111) to infliximab (IFX) compared to non-responders (N = 44). The addition of anti-CENPF antibodies to demographic and clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate responders, showing an area under the curve (AUC) of 0.756 (95% CI [0.639-0.874], p = 0.001). A further meta-analysis demonstrated the significant association of anti-CENPF levels with the patient's subsequent response to IFX, showing a standardized mean difference (SMD) of -0.65 (95% CI [-1.02;-0. 27], p = 0.018). CONCLUSIONS: Our study reveals for the first time the potential of circulating anti-CENPF antibodies to predict the clinical response to IFX before starting the treatment. This finding could be potentially useful to guide therapeutic decisions and may lead to further studies focusing on the role of CENPF on RA pathology.
32501655 Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Art 2020 Oct OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) are a hallmark of seropositive rheumatoid arthritis (RA). Yet, the precise disease-relevant autoantigens that are targeted by ACPAs remains a matter of debate. This study utilized patient-derived monoclonal ACPAs, rather than serum autoantibody analysis, to characterize the multireactivity to different protein modifications and to reveal autoantibody subsets in patients with RA. METHODS: Twelve human monoclonal ACPAs (positive by the second-generation cyclic citrullinated peptide test) were generated from 6 RA patients, and a head-to-head comparison of their reactivities was performed. For profiling, we used a complementary DNA-based protein array (Engine GmbH) and 3 peptide-screening platforms with RA autoantigens (Thermo Fisher Scientific), citrullinated and carbamylated peptides (NimbleGen/Roche), or histone-derived peptides with different posttranslational modifications (JPT Histone Code), covering >207,000 peptides (>7,800 gene products). RESULTS: The fine-specificity profiles of the investigated ACPAs varied, but all of the monoclonal ACPAs displayed multireactivity to a large number of citrullinated peptides/proteins, each characterized by specific binding properties. ACPA subsets could be defined by clone-distinct consensus binding motifs (e.g., Cit-Gly, Gly-Cit, or Arg-Cit-Asp), with the most common ACPA recognition being that of a Gly in the +1 flanking position, but with additional amino acid preferences. For ACPA protein recognition, we observed a preference for citrullinated RNA-binding proteins with high Arg/Gly content. Six of the 12 ACPA clones also bound acetylated lysine (KAc) or homocitrulline peptide motifs, displaying a similar affinity or higher apparent affinity than that for citrullinated peptides. CONCLUSION: ACPAs and anti-modified protein autoantibodies represent overlapping facets of RA autoimmunity and bind to a wide variety of modified proteins, extending well beyond the historically recognized set of RA autoantigens. So far, KAc reactivity has been detected only in the context of anti-carbamylated and anti-citrullinated peptide autoantibody responses, postulating the existence of hierarchies of autoreactivity in RA. Future investigations of ACPA fine specificities and functionality should take into consideration the presence of consensus Cit/Carb/KAc motifs and the multireactivity of these autoantibodies in patients with RA.
32621659 Physiologic Target, Molecular Evolution, and Pathogenic Functions of a Monoclonal Anti-Cit 2020 Dec OBJECTIVE: In plasma from a patient with rheumatoid arthritis (RA), we previously isolated a human monoclonal anti-citrullinated protein antibody (ACPA), CCP-Ab1, that recognizes various citrullinated antigens. In this study, we aimed to explore the physiologic target of CCP-Ab1 and the role of molecular evolution, through affinity maturation, of this ACPA in the onset and the exacerbation of RA. METHODS: The target protein of CCP-Ab1 was identified in the plasma of a patient with RA and purified under native conditions. Germline-reverted (GL-rev) CCP-Ab1 was generated, and its reactivity was compared to that of mature CCP-Ab1. The functions of CCP-Ab1 and GL-rev CCP-Ab1 in the onset or exacerbation of autoimmune arthritis were analyzed using autoimmune arthritis-prone SKG mice. RESULTS: CCP-Ab1 bound citrullinated fibrinogen under native conditions. In cultures with GL-rev CCP-Ab1, the binding affinity to citrullinated fibrinogen was drastically reduced (P < 0.05). The elements implicated in GL-rev CCP-Ab1 binding to a citrullinated peptide, cfc1-cyc, were almost identical to those implicated in CCP-Ab1 binding. In arthritis-prone SKG mice, CCP-Ab1, but not GL-rev CCP-Ab1, induced significant exacerbation of experimental arthritis (P < 0.05). Increased production of interleukin-6, both in the joint tissue and in the serum, was observed in SKG mice treated with CCP-Ab1 compared to those treated with GL-rev CCP-Ab1 (P < 0.05). Furthermore, the immune complex formed by CCP-Ab1 and fibrinogen was detected at higher concentrations in the synovial tissue of SKG mice administered CCP-Ab1 (P < 0.05 versus control treatment groups). CONCLUSION: These data show that germline-encoded CCP-Ab1, which binds weakly to citrullinated fibrinogen, undergoes hypermutation through the activation of naive B cells by citrullinated peptides/proteins, thereby stimulating high reactivity to citrullinated fibrinogen. These findings deepen our understanding of the role of molecular evolution of ACPAs in the onset and exacerbation of RA.
32222930 Role of depressive symptoms in the health-related quality of life of Venezuelan patients w 2020 Aug INTRODUCTION/OBJECTIVE: To examine the effect of depressive symptoms on health-related quality of life (HR-QoL) in Venezuelan patients with rheumatoid arthritis (RA). METHODS: HR-QoL was assessed in a cross-sectional, single-center study of 212 consecutive Venezuelan patients with RA (1987 American College of Rheumatology criteria) using the Medical Outcomes Study Short Form (SF-36), which includes a Physical Composite Scale (PCS) and a Mental Composite Scale (MCS); depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Covariates included socio-demographics, comorbidities, disease characteristics, body mass index, and disability. Unadjusted and multivariable linear regression analysis were used to determine the effect of depressive symptoms on HR-QoL. RESULTS: Mean age was 50.2 years and 89.6% were female. Twenty-five percent of patients had depressive symptoms. In the multivariable regression analysis, the presence of depressive symptoms changed the mental SF-36 scores by - 4.81 (p = 0.0052) and the physical SF-36 scores by - 3.33 (p = 0.0527). Other factors significantly associated with scores on the PCS of the SF-36 were functional class, disability and job loss due to RA. CONCLUSIONS: The presence of depressive symptoms negatively affected the HR-QoL in our patients, with a predominant effect on the MCS of the SF-36. The PCS of the SF-36 was mainly affected by those symptoms related to the functional impairment and inflammatory activity of the disease. The routine assessment and early treatment of depressive symptoms, targeting mental and mood manifestations, may improve the HR-QoL and thus contribute to healthier outcomes in Venezuelan RA patients.
31694750 Long noncoding RNA FER1L4 regulates rheumatoid arthritis via targeting NLRC5. 2020 Jul OBJECTIVES: Rheumatoid arthritis (RA) is a systematic autoimmune disease that cardinally affects the joints and other organs. Many people all over the world are suffering from the disease and no effective treatment has been established. Fibroblast-like synoviocytes (FLSs) play a critical role in the occurrence and development of RA. Long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to participate in various cancers as a tumour suppressor. However, its clinical significance and biological role in RA is completely unknown. METHODS: RT-qPCR or FISH were used to examine the expression of FER1L4 NLRC5, FER1L4 and inflammatory cytokine levels in synovial tissues (STs) from patients with RA or RA FLSs. Western blot was applied to examine the expression of NLRC5 and inflammatory cytokine levels in synovial tissues (STs) from patients with RA or RA FLSs. BrdU staining and MTT assay were used to examine the cell proliferation ability. The methylation-specific PCR was performed to analyse the methylation levels. RESULTS: The level of FER1L4 significantly reduced in STs and FLSs, whereas the nucleotide oligomerisation domain-like receptors 5 (NLRC5) levels were increased. Overexpression of FER1L4 can decreased the level of NLRC5 and inflammatory cytokine level. The FER1L4 gene promoter was significantly methylated in RA STs and FLSs. More importantly, treatment with methylation inhibitor 5-aza-2-deoxycytidine (5-azadC) inhibited hypermethylation of FER1L4 promoter and the expression of NLRC5. CONCLUSIONS: These results indicated that FER1L4 regulates RA via targeting NLRC5 potentially. Therefore, this study may provide a candidate therapeutic target for RA.
32666652 Promoting engagement in physical activity in early rheumatoid arthritis: A proof-of-concep 2020 Dec OBJECTIVE(S): The aim of this study is to test the feasibility and acceptability of promoting engagement in physical activity in early rheumatoid arthritis (PEPA-RA) to inform a future trial. DESIGN: A 'proof of concept' study was carried out. SETTING: This study was conducted in community hospitals delivered by musculoskeletal primary care physiotherapists. PARTICIPANTS: Participants were 12 adults with rheumatoid arthritis (RA) diagnosed 6-24 months previously (nine females, three males; mean age 58 years, range 23-79). INTERVENTION: The intervention consisted of five sessions, that is, four group sessions and one individual session facilitated by a physiotherapist over 12 weeks including patient education and support for behaviour change as well as supervised practical exercise. MAIN OUTCOMES: The main outcomes were attendance, completion of outcome measures, adverse events, and participant and physiotherapist feedback views relating to the intervention. RESULTS: Overall attendance was 85%, with sessions missed due to illness or RA flare. Outcome measure completion ranged from 83% to 100%. There were no clinically meaningful changes in pain or function at 12 weeks, but mean 6-min walk distance improved from 394 to 440 m. No serious adverse events were reported, and participants were generally positive about the intervention. Suggested minor modifications for the group sessions included venue accessibility and ensuring that physical activity time was protected. Several participants indicated that they would have liked to receive the intervention earlier following diagnosis. CONCLUSIONS: PEPA-RA and the outcomes appear feasible and acceptable. Overall, small beneficial effects were noted at 12 weeks for most outcomes. Challenges to recruitment resulted in a smaller than anticipated sample size, and the majority of participants were active at baseline indicating that future recruitment needs to target less active individuals.
33185703 Carpal tunnel syndrome in patients with rheumatoid arthritis and psoriatic arthritis: an e 2021 Feb This study aimed to investigate the carpal tunnel syndrome (CTS) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), compare the electrophysiological and ultrasonographic findings and evaluate related variables. Cut-off value of median nerve cross-sectional area (MCSA) was determined for the diagnosis of CTS. 70 RA patients, 39 PsA patients, a control group of 70 healty people were included in this study. Demographic characteristics, disease activity and functional status were recorded. Patients were referred for nerve conduction studies performed according to the American Academy of Neurology standards. Sonographic examination was carried on for MCSA evaluation. The mean age of patients was 51.87 ± 8.47, 50.61 ± 11.33, 49.75 ± 10.52 years and female ratio was 72.9%, 71.8%, 75.7% in RA, PsA and controls, respectively. Electrophysiologically, CTS frequency was found to be 13.2%, 15.4%, 3.5% in RA, PsA, control group, respectively, and a significant difference was found compared to the control group (p < 0.05). Ultrasonographically MCSA was measured as 8.52 ± 2.19 mm(2), 8.97 ± 2.41 mm(2), 7.09 ± 1.83 mm(2) in RA, PsA, control group, respectively, a significant difference was observed compared to the control group (p < 0.05). As a result of the Receiver Operating Characteristics analysis, the thereshold value of MCSA for CTS was determined as 10.5 mm(2).The frequency of CTS was found to be 30% in RA and 41% in PsA. The frequency of CTS with both ENMG and USG (MCSA) were higher in patients with RA and PsA as compared to the control group. Although it was not statistically significant, CTS frequency was higher in PsA than RA. To our knowledge this is the first study assessing CTS in patients with PsA, and adressing MCSA cut off value for CTS diagnosis in RA and PsA.
32349791 Impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections 2020 Apr 29 OBJECTIVES: To systematically review the impact of tapering targeted therapies (bDMARDs or JAKis) on the risk of serious infections and severe adverse events (SAEs) in patients with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) in remission or low disease activity (LDA) state. MATERIALS AND METHODS: A meta-analysis based on a systematic review of PubMed, Embase, Cochrane, until August 2019, as well as relevant databases of international conferences, was used to evaluate the risk difference (RD) at 95% confidence interval (95% CI) of incidence density of serious infections, SAEs, malignancies, cardiovascular adverse events (CV AEs), or deaths after tapering (dose reduction or spacing) compared to continuation of targeted therapies. RESULTS: Of the 1957 studies initially identified, 13 controlled trials (9 RA and 4 SpA trials) were included in the meta-analysis. 1174 patient-years were studied in the tapering group (TG) versus 1086 in the usual care group (UC). There were 1.7/100 patient-year (p-y) serious infections in TG versus 2.6/100 p-y in UC (RD (95% CI) 0.01 (0.00 to 0.02), p = 0.13) and 7.4/100 p-y SAEs in TG versus 6.7/100 p-y in UC (RD 0.00 (- 0.02 to 0.02), p = 0.82). The risk of malignancies, CV AEs, or deaths did not differ between the tapering and the usual care groups. Subgroup analysis (RA and SpA) detected no significant differences between the two groups. CONCLUSION: We could not show significant impact of tapering bDMARD or JAKi over continuation concerning the risk of serious infections, SAEs, malignancies, CV AEs, or deaths in RA and SpA patients in remission or LDA state.
31043549 A Population-level Analysis of the Differing Effects of Rheumatoid Arthritis and Spondyloa 2020 Feb OBJECTIVE: The effects of rheumatoid arthritis (RA) and spondyloarthritis (SpA) on maternal and neonatal outcomes at a population level have not previously been well compared. METHODS: A contemporary pregnancy cohort of 312,081 women and corresponding birth events was assembled for the province of Alberta from the random selection of 1 live birth event per woman. We identified 3 groups: (1) no inflammatory arthritis (no IA, n = 308,989), (2) RA (n = 631), and (3) SpA (n = 2461). We compared maternal and neonatal outcomes, comorbid conditions, and medication use among the 3 groups. Multivariable logistic regression models evaluated the independent association between RA and SpA, relative to no IA, and the outcomes of small for gestation age (SGA) and hypertensive disorders during pregnancy. RESULTS: Pregnant women with RA were significantly more likely to have preterm delivery (13.5%), cesarean delivery (33.9%), hypertensive disorders in pregnancy (10.5%), and SGA babies (15.6%), compared to pregnant women with either SpA or no IA. Nonsteroidal antiinflammatory drugs and corticosteroid use were significantly higher in pregnant women with RA compared to the other groups. Women with RA were significantly more likely to have an SGA baby (OR 1.51, 95% CI 1.21-1.88; p < 0.01), and hypertensive disorder in pregnancy (OR 1.51, 95% CI 1.16-1.97; p < 0.01), compared to women with no IA, while no difference was found between women with SpA and those with no IA. CONCLUSION: Women with RA have a higher risk of worse maternal and neonatal outcomes, whereas the risk of these events is similar between women with and without SpA.
32896247 Mass-spectrometric identification of carbamylated proteins present in the joints of rheuma 2021 May OBJECTIVES: Antibodies targeting post-translationally modified proteins, such as anti-carbamylated protein antibodies (anti-CarP antibodies) are present in the sera of rheumatoid arthritis (RA) patients. These autoantibodies associate with increased risk of RA development and with severity of joint destruction. It is not known which proteins in the RA joint are recognised by anti-CarP antibodies. Therefore, we investigated the presence and identity of carbamylated proteins in the human (inflamed) joint. METHODS: We obtained synovium, cartilage and synovial fluid from RA joints. Cartilage and synovium were obtained from controls. Samples were processed and used for immunohistochemistry or mass-spectrometric analysis to investigate the presence of carbamylated proteins. Anti-CarP antibody reactivity towards identified carbamylated proteins was tested by ELISA. RESULTS: Immunohistochemistry showed extensive staining of RA and control synovial tissue. Whole proteome analyses of the joint tissues revealed a large number of carbamylated peptidyllysine residues. We identified many carbamylated proteins in cartilage and were also able to detect carbamylation in synovial tissue and synovial fluid. Carbamylation was not exclusive to the RA joint and was also present in the joints of controls. Anti-CarP antibodies in the sera of RA patients were able to recognise the identified carbamylated proteins. CONCLUSIONS: We conclude that numerous carbamylated proteins are present in the RA joint. These carbamylated proteins can be recognised by anti-CarP antibodies, substantiating the notion that anti-CarP antibodies may play a role in the pathogenesis of RA.
32907589 Evaluation of the content validity index of the Australian/Canadian osteoarthritis hand in 2020 Sep 9 BACKGROUND: The Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Patient-Rated Wrist/Hand Evaluation (PRWHE) and the Thumb Disability Exam (TDX) are patient-reported outcome measures (PROM) designed to assess pain and hand function in patients with hand arthritis, hand pain and disability, or thumb pathology respectively. This study evaluated the content validity of AUSCAN, PRWHE and TDX in people with hand arthritis. METHODS: This study enrolled participants with hand arthritis to rate the items of all 3 PROM in terms of relevance and clarity. The Content Validity Index (CVI) was computed for each item in each scale (I-CVI) as well as for the overall scale (S-CVI). Kappa was used to determine the inter-rater agreement among the raters. RESULTS: Overall, 64 individuals with hand arthritis (27% with OA, 67% with rheumatoid arthritis and 6% with psoriatic arthritis) participated in the study. The I-CVI for all items and all scales were very high (I-CVI > 0.76) and the modified Kappa agreement among the raters demonstrated excellent agreement (k > 0.76). The S-CVI for all PROMs was very high for relevance (AUSCAN = 0.92, 95% CI 0.90 to 0.94; PRWHE = 0.85, 95% CI 0.82 to 0.88 and TDX = 0.87, 95% CI 0.85 to 0.89) and for clarity (AUSCAN = 0.99, 95% CI 0.98 to 1.00; PRWHE = 0.95, 95% CI 0.93 to 0.97 and TDX = 0.91, 95% CI 0.89 to 0.94), respectively. CONCLUSIONS: This study demonstrated very high content validity indices for the AUSCAN, PRWHE and TDX; with strong consensus across raters. This augments prior studies demonstrating appropriate statistical measurement properties, to provide confidence that all three measures assess important patient concepts of pain and disability.
31678218 Skeletal muscle fat in individuals with rheumatoid arthritis compared to healthy adults. 2020 Jan OBJECTIVE: To compare skeletal muscle fat (SMF), intermuscular adipose tissue (IMAT) and subcutaneous adipose tissue (SAT) between individuals with rheumatoid arthritis (RA), and healthy individuals of the same age, and healthy individuals at least 10 years older than those with RA. METHODS: Two cross-sectional studies. In the first study, RA subjects were matched by age, sex, and BMI with healthy adults. In the second, RA subjects were matched by sex and BMI to adults 10-20 years older. SMF, IMAT and SAT were measured with Computed Tomography images of the mid-thigh region. We used parametric or non-parametric related-sample tests to compare fat accumulation between RA subjects and healthy adults. RESULTS: In the first study SMF was significantly higher in the RA cohort compared to their age-matched healthy counterparts (mean difference = -3.5 HU (95% -6.2, -0.9), p = 0.011), but IMAT and SAT were similar between cohorts. In the second study, SMF, IMAT and SAT were not significantly different between the RA and matched older healthy cohorts. In both studies, there were no significant differences in mid-thigh muscle area between RA subjects and healthy adults. CONCLUSION: SMF accumulation in RA was higher than in healthy individuals of similar age, sex, BMI. Accumulation of fat within and around the muscles in RA was not different compared to the matched healthy older individuals, indicating that muscle fat accumulation in RA might mimic a pattern not different from healthy aging.
31952907 EZH2 deficiency attenuates Treg differentiation in rheumatoid arthritis. 2020 Mar The chromatin modifier enhancer of zeste homolog 2 (EZH2) methylates lysine 27 of histone H3 (H3K27) and regulates T cell differentiation. However, the potential role of EZH2 in the pathogenesis of rheumatoid arthritis (RA) remains elusive. We analyzed EZH2 expression in PBMC, CD4(+) T cells, CD19(+) B cell, and CD14(+) monocytes from active treatment-naïve RA patients and healthy controls (HC). We also suppressed EZH2 expression using EZH2 inhibitor GSK126 and measured CD4(+) T cell differentiation, proliferation and apoptosis. We further examined TGFβ-SMAD and RUNX1 signaling pathways in EZH2-suppressed CD4(+) T cells. Finally, we explored the regulation mechanism of EZH2 by RA synovial fluid and fibroblast-like synoviocyte (FLS) by neutralizing key proinflammatory cytokines. EZH2 expression is lower in PBMC and CD4(+) T cells from RA patients than those from HC. EZH2 inhibition suppressed regulatory T cells (Tregs) differentiation and FOXP3 transcription, and downregulated RUNX1 and upregulated SMAD7 expression in CD4(+) T cells. RA synovial fluid and fibroblast-like synoviocytes suppressed EZH2 expression in CD4(+) T cells, which was partially neutralized by anti-IL17 antibody. Taken together, EZH2 in CD4(+) T cells from RA patients was attenuated, which suppressed FOXP3 transcription through downregulating RUNX1 and upregulating SMAD7 in CD4(+) T cells, and ultimately suppressed Tregs differentiation. IL17 in RA synovial fluid might promote downregulation of EZH2 in CD4(+) T cells. Defective EZH2 in CD4(+) T cells might contribute to Treg deficiency in RA.
32914364 Screen the Effective Components of Lycopodii herba on Rheumatoid Arthritis with the Aid of 2020 Dec Lycopodii herba (SJC), a traditional Chinese medicine, has the effect of dispelling wind and eliminating dampness (a therapeutic principle and method of traditional Chinese medicine for rheumatoid arthritis), relaxing tendon and activating collaterals. However, the major effective components and its therapeutic mechanism were unclear. In this study, different SJC samples with slightly different compositions were prepared by extracting with different concentrations of ethanol. Then, the therapeutic effects on rheumatoid arthritis (RA) of different SJC samples were evaluated. Finally, the spectrum-effect relationship between UPLC-Q-TOF/MS fingerprints and the effect of RA was explored to screen the effective components. Western blotting was used to study the potential mechanism. The volume of hind paw and the level of RF, TNF-α, and IL-1β were lower after administrating with different SJC samples, compared with the model group. Histopathological findings also confirmed that SJC could relieve the symptoms of RA. Combined with identification of the components in plasm from SJC, lycojaponicumin C, des-N-methyl-α-obscurine, 8β-acetoxy-12β-hydroxy-lycopodine or 8β-acetoxy-11α-hydroxy-lycopodine or 8β-hydroxy-11α-acetoxylycopodine were considered to be the major effective components. The mechanism may be related to AChE/NF-κB signaling pathway. This work provides a general method to screen the potential effective components of herb medicines and would be benefit to understand the mechanism of SJC for the treatment of RA.
32891538 Helicobacter pylori infection and autoimmune diseases; Is there an association with system 2021 Jun Autoimmune diseases are considered as one of the most important disorders of the immune system, in which the prolonged and chronic processes eliminate self-tolerance to the auto-antigens. The prevalence of autoimmune diseases has been increasing worldwide in the recent years. According to the literature, biological processes such as the host genome, epigenetic events, environmental condition, drug consumption, and infectious agents are the most important risk factors that make the host susceptible to the development of autoimmune diseases. In the recent years, the role of Helicobacter pylori in the induction of autoimmune diseases has attracted extensive attention. Via molecular mimicry, epitope spreading, bystander activation, polyclonal activation, dysregulation in immune response, and highly immune-dominant virulence, such as cagA, H. pylori causes tissue damage, polarity, and proliferation of the host cells leading to the modulation of host immune responses. Moreover, given the large population worldwide infected with H. pylori, it seems likely that the bacterium may develop into autoimmune diseases through dysregulation of the immune response. The frequency and relationship between H. pylori infection and systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis, and autoimmune pancreatitis were evaluated using the data from 43 studies involving 5052 patients. According to statistical analysis it is probable that infection with more virulent strains of H. pylori (such as H. pylori cagA positive) can increase the risk of autoimmune diseases. In addition, it was shown that infection with H. pylori can prevent the development of atrophic gastritis by stimulating inflammation in the gastric antrum. However, future studies should confirm the validity of this study.
32772027 IRF9 Affects the TNF-Induced Phenotype of Rheumatoid-Arthritis Fibroblast-Like Synoviocyte 2020 OBJECTIVE: To discuss how IRF9 affects the fibroblast-like synoviocytes (FLS) in TNF-induced rheumatoid arthritis (RA) via the SIRT-1/NF-κB signaling pathway. METHODS: RA-FLS were isolated and divided into control, sh-IRF9, TNF, TNF + sh-Ctrl, TNF + sh-IRF9, TNF + sh-SIRT1, and TNF + sh-IRF9 + sh-SIRT1 groups. Biological features of FLS were evaluated by MTT, wound healing, and Transwell assays, respectively. Cell apoptosis and cycle were assessed flow cytometrically. Inflammatory cytokines were determined through enzyme-linked immunosorbent assay (ELISA), while IRF9 expression and SIRT1/NF-κB signaling pathway activity were measured by Western blotting. RESULTS: TNF increased IRF9 expression as well as NF-κB signaling activity and down-regulated SIRT1 of RA-FLS. Silencing IRF9 resulted in up-regulation of SIRT1 and blocked NF-κB signaling, with significant decreases in TNF-induced cell viability, migration, and invasion, prominent enhancement in apoptosis and the proportion of cells in G0/G1 phase, but a decrease in the proportion of cells in S and G2/M phases, and reduced levels of inflammatory cytokines. However, these changes were totally abolished after silencing SIRT1, i.e., the IRF9 shRNA-induced inhibitory effect on the growth of RA-FLS was reversed. CONCLUSION: Silencing IRF9 curbs the activity of the NF-κB signaling pathway via up-regulating SIRT-1, to further suppress TNF-induced changes in the malignant features of RA-FLS, and the secretion of inflammatory cytokines, with the promoted apoptosis.