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ID PMID Title PublicationDate abstract
33175207 The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic revie 2021 May The objective is to determine the global population prevalence of rheumatoid arthritis (RA) based on population-based studies and assess factors that influence RA prevalence estimates. Four electronic databases were searched (ProQuest Central, MEDLINE, Web of Science, and EMBASE) for peer-reviewed English publications that report prevalence estimates of RA from 1980 and 2019. We included case-control studies, cross-sectional studies, and prospective or retrospective cohort studies in our search strategy. A random-effect meta-analysis model was used to produce the pooled prevalence estimates. The potential between-study heterogeneity was identified using sensitivity analysis, sub-group and meta-regression analyses. A total of 67 studies were included in the meta-analysis, containing 742,246 RA patients and 211,592,925 healthy controls in the study period. The global RA prevalence estimate was 0.46% (95% confidence interval [CI] 0.39-0.54; I(2) = 99.9%) with a 95% prediction interval (0.06-1.27). The RA point-prevalence was 0.45% (95% CI 0.38-0.53%) between 1986 and 2014, while the pooled period-prevalence was 0.46% (95% CI 0.36% and 0.57%) from 1955 to 2015. The highest RA pooled prevalence (0.69%; 95% CI 0.47-0.95) was derived from linked data source studies. Based on meta-regression, the factors that explain the studies' heterogeneity of RA prevalence, including geographical location, the risk bias assessment of studies and sample size. The global prevalence of RA between 1980 and 2019 was 460 per 100,000 population, with variations due to geographical location and study methodology. Linked data are the preferred method to estimate RA population prevalence as they provide the best case ascertainment.
32491275 "To be lonely in your own loneliness": The interplay between self-perceived loneliness and 2020 Dec OBJECTIVE: Loneliness has a negative impact on physical health, and rheumatoid arthritis symptoms can lead to social isolation. However, there is a lack of research exploring patients' perspectives on self-perceived loneliness in everyday life with rheumatoid arthritis. The purpose of this study was to gain insight into the meaning and importance of self-perceived loneliness among adult patients diagnosed with rheumatoid arthritis. METHODS: This study was designed as a qualitative, exploratory interview study using a narrative framework. Semi-structured interviews were conducted with Danish adults with rheumatoid arthritis. All interviews were recorded, transcribed verbatim, and analyzed within a narrative thematic framework. RESULTS: Ten women and seven men were interviewed, aged between 18 and 73 years and a disease duration between 6 months and 40 years. Three themes were identified during the analysis: (1) explanations of loneliness in everyday life with rheumatoid arthritis, (2) disclosing or disguising loneliness, and (3) feelings of loneliness in social life. CONCLUSION: The findings from this study show that loneliness can be burdensome when living with RA. Narratives of loneliness can be hard for patients to disclose, so health care practitioners should take responsibility for legitimizing this subject. A narrative approach in consultations may be helpful to support patients and to encourage a dialogue about loneliness in everyday life with rheumatoid arthritis.
30821924 Qualitative Study of Treatment Preferences for Rheumatoid Arthritis and Pharmacotherapy Ac 2020 Apr OBJECTIVE: To explore patient preferences that influence decision-making in the management of rheumatoid arthritis (RA) by indigenous patients living in southern Alberta, Canada. METHODS: We conducted a qualitative narrative-based study within a social constructivist framework. Thirteen in-depth interviews with indigenous patients with RA who had attended 1 of 3 rheumatology practices in southern Alberta (1 rural and 2 urban) were completed. Codes generated through 2 phases of analysis were condensed into main themes, triangulated, and used to produce theoretical statements. RESULTS: Patients preferred to use a combination of nonpharmacologic and pharmacologic treatments to manage their RA. Nonpharmacologic treatments included physical, mental, emotional, and spiritual strategies. Patients' preferences for taking medications varied and were influenced by factors that were clinical (i.e., trust in health providers and understanding drugs' mechanisms of action, benefits, harms, and administration burden), familial (i.e., support), and societal (i.e., access to medications and stigmatization of drug dependency). CONCLUSION: Indigenous patients apply a holistic approach to the nonpharmacologic management of RA. Increases in preferences for RA medications could be supported through enhanced communication strategies to increase patient understanding of medication effects and health provider recognition of societal and familial influences on patient decisions. A patient-provider relationship based on trust was fundamental to reaching mutual understanding and should be fostered by models of practice that promote cultural safety, empathy, compassion, openness, acknowledgment, and respect of cultural differences.
31938882 Glucocorticoid use is an independent risk factor for developing sarcopenia in patients wit 2020 Jun INTRODUCTION: Patients with rheumatoid arthritis (RA) are at higher risk of sarcopenia because of joint dysfunction and chronic inflammation. The present study aimed to investigate the predictors or risk factors for developing sarcopenia in RA patients using the prospective observational CHIKARA database. We hypothesized that older age, higher disease activity, lower physical function, and glucocorticoid (GC) use are risk factors for sarcopenia. METHODS: A total of 100 consecutive RA patients participated in the CHIKARA study. Their body compositions were examined using a body composition analyzer. Laboratory data, disease activity, physical function, and treatment were investigated. Sarcopenia was assessed at baseline and at 1 year. Predictors or risk factors for sarcopenia development at 1 year were investigated by univariate and multivariate analyses. RESULTS: Of 68 patients without sarcopenia at baseline, 9 (13.4%) developed sarcopenia over the year. Univariate analysis showed that age (r = 0.28, p = 0.022), average GC dose over the year (r = 0.25, p = 0.043), and body mass index (r = - 0.28, p = 0.019) were significantly associated with the development of sarcopenia. Average GC use at ≥ 3.25 mg/day was a significant factor on multivariate analysis (odds ratio 8.81, 95% confidence interval 1.14-67.9, p = 0.037). CONCLUSIONS: RA patients using GCs at an average dose ≥ 3.25 mg/day over 1 year were at higher risk for developing sarcopenia. Reduction or withdrawal of GCs may prevent sarcopenia.Key Points• Patients with RA are at higher risk of sarcopenia.• Predictors or risk factors for developing sarcopenia over 1 year in RA patients were investigated using the prospective observational CHIKARA database.• RA patients using GCs at an average dose ≥ 3.25 mg/day over 1 year were at higher risk for developing sarcopenia.• Reduction or withdrawal of GCs may be essential to prevent sarcopenia.
31987855 MicroRNA let-7g-5p alleviates murine collagen-induced arthritis by inhibiting Th17 cell di 2020 Apr Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease with complicated pathogenesis. IL-17-producing T helper cells (Th17) are important players in the RA process. Despite numerous researches have proven that microRNAs (miRNAs) are crucial to regulate autoimmune diseases including RA, the effect of miRNAs on Th17 cell differentiation and function in the RA progress is not clear. Here, our results showed that the expression of miRNA let-7g-5p was substantially lower in RA patients and CIA mice compared with healthy controls, accompanied by the increased Th17 cell population. Furthermore, the inhibition of let-7g-5p on Th17 cell differentiation and function were verified in vitro. Notably, the disease severity in CIA mice was significantly alleviated after the treatment of let-7g-5p mimics. In addition, let-7g-5p mimics treatment markedly down-regulated the frequency of Th17 cells in CIA mice. Taken together, our findings indicate that let-7g-5p can ameliorate CIA through blocking the differentiation of Th17 cells, which may be a novel strategy to treat autoimmune diseases such as RA.
32638516 Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two 2020 Dec OBJECTIVE: This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts. METHODS: An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH-axSpA) was determined by enzyme-linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort. RESULTS: We identified antibodies to 9 novel UH-axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH-axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH-axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C-reactive protein. Testing for antibodies to these 3 UH-axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%. CONCLUSION: Antibodies to 3 UH-axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.
31694746 Validation of two frailty questionnaires in older patients with rheumatoid arthritis: a cr 2020 May OBJECTIVES: Several questionnaires exist to assess frailty, a geriatric syndrome. None of these has been validated in older patients with rheumatoid arthritis (RA). Our objective was to assess aspects of validity of two frailty questionnaires: Groningen Frailty Indicator (GFI) and Geriatric 8 (G8) among RA patients. METHODS: In a cross-sectional study among patients ≥65 years information was collected on socio-demographics, disease characteristics including comorbidities and physical function and on frailty using the GFI and G8. Content validity was assessed by linking items of the GFI and G8 to the International Classification of Functioning, Disability and Health (ICF). Classic psychometric methods were used to test hypotheses on construct validity and interpretability. RESULTS: Eighty patients (74.6 years (SD 5.9); 66% female) participated. The GFI has more items on social and mental functions; the G8 more on functions of the digestive system (e.g. nutritional status). As hypothesised, correlations (r) with physical function (RGFI=0.54; RG8=0.56) and disease activity (RGFI=0.24; RG8=0.36) were moderate to weak. However, correlations with age (RGFI=0.20; RG8=0.11) or comorbidities (RGFI=0.30; RG8=0.16) were lower than expected. Instrument-specific thresholds classified 43 (54%) of participants as frail on the GFI and 44 (55%) on the G8; 33 (41%) were frail on both instruments. CONCLUSIONS: The GFI and G8 differ in content with more emphasis on nutritional status for the G8. Both instruments are insensitive to age and comorbidities. Before deciding on their usefulness in RA, their predictive validity for mortality and resource utilisation independent of disease activity and physical function should be further evaluated.
32425508 Effect of Eriodictyol on Collagen-Induced Arthritis in Rats by Akt/HIF-1α Pathway. 2020 PURPOSE: The aim of the experiment was to explore the effect of eriodictyol (ERI) on arthritis. METHODS: We established a rat model of collagen-induced rheumatoid arthritis (CIA) using type II collagen plus Freund's complete adjuvant. We evaluated the degree of paw swelling, joint pathology, inflammatory cytokine levels, and the Akt/hypoxia-inducible factor (HIF)-1α signaling pathway in the CIA rats. RESULTS: ERI significantly ameliorated joint swelling; improved joint pathology; and suppressed the release of interleukin-6, interleukin-1 beta, and tumor necrosis factor-alpha. Moreover, ERI inhibited the Akt/HIF-1α pathway in the joints of rats and in lipopolysaccharide-treated RAW264.7 cells. CONCLUSION: ERI ameliorated arthritis in a manner involving the Akt/HIF-1α signaling pathway.
32100960 Exposure-Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activi 2020 Jul Anti-tumor necrosis factor (anti-TNF) drugs are often prescribed for the treatment of rheumatoid arthritis (RA) and other immune-mediated inflammatory diseases. Although this treatment has been shown to be effective in many patients, up to 40% of patients do not achieve disease control. Drug concentration in plasma may be a factor affecting the observed variability in therapeutic response. In this study, we aimed to identify the plasma concentrations of the anti-TNF certolizumab pegol (CZP), associated with improvement in disease activity in patients with RA. Data were pooled from three randomized, controlled clinical trials with a combined total of 1,935 patients analyzed. Clinical outcomes of low disease activity (LDA) and remission were defined as Disease Activity Score in 28 joints with C-reactive protein (DAS28(CRP)) ≤ 2.7 and < 2.3, respectively. Quartile analysis results indicated that there may be an exposure-response relationship between CZP concentration and LDA/remission outcomes at weeks 12 and 24; the association was strongest for LDA (P < 0.05). Receiver operating characteristic (ROC) analysis showed that CZP concentrations ≥ 28.0 μg/ml at week 12, and ≥ 17.6 μg/ml at week 24, were associated with a greater likelihood of achieving LDA/remission outcomes. Although confirmatory studies are warranted to define the optimal CZP therapeutic range at weeks 12 and 24, these data indicate that CZP concentrations may be associated with improvement of disease activity.
32458832 Electrochemical biosensor for the simultaneous determination of rheumatoid factor and anti 2020 Jul 7 This paper reports a dual electrochemical biosensor involving carboxylated- or neutravidin-functionalized magnetic microbeads and dual screen-printed carbon electrodes for the simultaneous determination of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCPA) autoantibodies used as biomarkers for the detection of rheumatoid arthritis autoimmune disease. Sandwich-type biosensors involving Fc fragments of IgG Fc(IgG) and biotinylated cyclic cytrullinated peptide (CCP-biotin) to form CCP-biotin-Neutr-MBs for the specific immobilization of RF and CCPA, respectively, as well as conjugation with HRP-IgM and HRP-IgG for RF and CCPA, respectively, were prepared. Amperometric detection was performed at -0.20 V vs. Ag pseudo-reference electrode using the H(2)O(2)/hydroquinone (HQ) system upon capturing the bioconjugates onto the corresponding working electrode (WE1 or WE2) of SPCdEs. The dual biosensor exhibits high sensitivity for RF and CCPA with LOD values of 0.8 and 2.5 IU mL(-1), respectively. The simultaneous determination can be completed in about two hours using a simple protocol and a sample volume (25 μL) four times smaller than that required by the ELISA method. The dual electrochemical biosensor was used for the determination of both target biomarkers in human serum.
32590796 Deep surgical site infection after posterior instrumented fusion for rheumatoid upper cerv 2020 Jun 26 INTRODUCTION: Patients with rheumatoid arthritis (RA) tend to be immunosuppressed due to RA itself and the therapeutic drugs administered. The management of surgical site infection (SSI) following upper cervical spinal instrumented fusion in RA patients is challenging; however, literature on the treatment for such conditions is scarce. We report 3 consecutive patients with RA, who developed deep SSI following upper cervical posterior fusion and were treated using antibiotic-loaded bone cement (ALBC). PATIENT CONCERNS: All 3 patients reported in the current study experienced compression myelopathy with upper cervical spinal deformity and received prednisolone and methotrexate for controlling RA preoperatively. The patient in Case 1 underwent C1-2 posterior fusion and developed deep SSI due to methicillin-sensitive Staphylococcus aureus at 3 months postoperatively; the patient in Case 2 underwent occipito-C2 posterior fusion and developed deep SSI due to methicillin-sensitive Staphylococcus aureus at 2 weeks postoperatively; and the patient in Case 3 underwent occipito-C2 posterior instrumented fusion and laminoplasty at C3-7, and developed deep SSI due to methicillin-resistant coagulase negative staphylococci at 3 weeks postoperatively. DIAGNOSIS: All patients developed deep staphylococcal SSI in the postoperative period. INTERVENTIONS: All 3 patients were treated using ALBC placed on and around the instrumentation to cover them and occupy the dead space after radical open debridement. OUTCOMES: The deep infection was resolved uneventfully after the single surgical intervention retaining spinal instrumentation. Good clinical outcomes of the initial surgery were maintained until the final follow-up without recurrence of SSI in all 3 cases. CONCLUSION: ALBC embedding spinal instrumentation procedure can be a viable treatment for curing SSI in complex cases, such as patients with RA who undergo high cervical fusion surgeries without implant removal.
32182406 Noninferiority Trials to Evaluate Drug Effects in Rheumatoid Arthritis. 2020 Aug OBJECTIVE: The increased availability of highly effective treatments in rheumatoid arthritis (RA) necessitates a reexamination of study designs evaluating new treatments. We undertook this study to discuss possible specifications and considerations of noninferiority (NI) trials assessing drug effects in RA. METHODS: We focused on the use of approved tumor necrosis factor inhibitors (TNFi) as potential active controls and reviewed previous placebo-controlled studies. We summarized the similarities in baseline characteristics and study design of the historical placebo-controlled studies used. After performing meta-analyses to estimate the effects of TNFi on symptoms, physical function, and radiographic progression in RA, we proposed NI margins and evaluated the feasibility of NI trials in this therapeutic setting. RESULTS: We determined that an NI trial comparing an experimental treatment to a TNFi using the symptomatic end point of the American College of Rheumatology 20% improvement criteria response can feasibly provide evidence of a treatment effect, with a 12% absolute difference as one possible appropriate NI margin. For change from baseline in the Health Assessment Questionnaire disability index score, reasonable margins range from 0.10 to 0.12. In evaluating radiographic progression, an appropriate margin and the corresponding feasibility of the trial are dependent on the selected active control and the expected variability in progression. CONCLUSION: Active-controlled studies in RA with justified NI margins can provide persuasive evidence of treatment effects on symptomatic, functional, and radiographic end points. Such studies can also provide reliable, controlled safety data and relevant information for treatment decisions in clinical practice. Thus, we recommend considering NI designs in future clinical trials in RA.
33007934 The Relevance of Selenium Status in Rheumatoid Arthritis. 2020 Sep 30 Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease that can cause joint damage. Among the environmental risk factors, diet plays an important role because it can aggravate or attenuate inflammation. Selenium (Se) is considered an essential trace element since it is a structural component of antioxidant enzymes; however, its concentration can be affected by diet, drugs and genetic polymorphisms. Studies have reported that RA patients have a deficient diet in some food groups that is associated with parameters of disease activity. Furthermore, it has been shown that there is an alteration in serum Se levels in this population. Although some clinical trials have been conducted in the past to analyze the effect of Se supplementation in RA, no significant results were obtained. Contrastingly, experimental studies that have evaluated the effect of novel Se nanoparticles in RA-induced models have shown promising results on the restoration of antioxidant enzyme levels. In particular, glutathione peroxidase (GPx) is an important selenoprotein that could have a modulating effect on inflammation in RA. Considering that RA patients present an inflammatory and oxidative state, the aim of this review is to give an overview of the current knowledge about the relevance of Se status in RA.
32310291 Circulating plasma metabolites and risk of rheumatoid arthritis in the Nurses' Health Stud 2020 Nov 1 OBJECTIVES: RA develops slowly over years. We tested for metabolic changes prior to RA onset using a large non-targeted metabolomics platform to identify novel pathways and advance understanding of RA development. METHODS: Two hundred and fifty-four incident RA cases with plasma samples drawn pre-RA onset in the Nurses' Health Study (NHS) cohorts were matched 1:2 to 501 controls on age, race, menopause/post-menopausal hormone use and blood collection features. Relative abundances of 360 unique, known metabolites were measured. Conditional logistic regression analyses assessed associations between metabolites and incidence of RA, adjusted for age, smoking and BMI, accounting for multiple comparisons. Subgroup analyses investigated seropositive (sero+) RA and RA within 5 years of sample collection. Significant metabolites were then tested in a female military pre-RA case-control study (n = 290). RESULTS: In the NHS, metabolites associated with RA and sero+RA in multivariable models included 4-acetamidobutanoate (odds ratio (OR) = 0.80/S.d., 95% CI: 0.66, 0.95), N-acetylputrescine (OR = 0.82, 95% CI: 0.69, 0.96), C5 carnitine (OR = 0.84, 95% CI: 0.71, 0.99) and C5:1 carnitine (OR = 0.81, 95% CI: 0.68, 0.95). These were involved primarily in polyamine and leucine, isoleucine and valine metabolism. Several metabolites associated with sero+RA within 5 years of diagnosis were replicated in the independent military cohort: C5 carnitine (OR = 0.55, 95% CI: 0.33, 0.92), C5:1 carnitine (OR = 0.62, 95% CI: 0.39, 0.99) and C3 carnitine (OR = 0.57, 95% CI: 0.36, 0.91). CONCLUSION: Several metabolites were inversely associated with incidence of RA among women. Three short-chain acylcarnitines replicated in a smaller dataset and may reflect inflammation in the 5-year period prior to sero+RA diagnosis.
30789095 Activated neutrophil carbamylates albumin via the release of myeloperoxidase and reactive 2020 Mar Objective: An anti-carbamylated albumin antibody was detected in rheumatoid arthritis (RA) patients, and its presence was associated with serum myeloperoxidase (MPO) levels, as we reported previously. Since MPO is a key enzyme for carbamylation and is released by neutrophil extracellular traps (NETs), we aimed to demonstrate that NETosis induces carbamylation.Methods: Human neutrophils were isolated from a healthy donor, pre-treated with or without diphenyleneiodonium (DPI, an inhibitor for the generation of reactive oxygen species (ROS)), Cl-amidine (a peptidylarginine deiminase inhibitor), 4-aminobenzoic acid hydrazide (4-ABAH, an MPO inhibitor), or GW311616A (a neutrophil elastase (NE) inhibitor), and incubated for 8 h with or without phorbol 12-myristate 13-acetate (PMA). Proteins in the medium were collected and the carbamylation of albumin was evaluated by Western blotting.Results: The carbamylation of albumin was detected in the culture medium of activated neutrophils. NETosis was observed under the stimulation by PMA. DPI and 4-ABAH inhibited the carbamylation of albumin and NETosis. GW311616A inhibited NETosis, but not carbamylation. Neither carbamylation nor NETosis was inhibited by Cl-amidine.Conclusion: Activated neutrophils may carbamylate ambient albumin, and this is dependent on ROS and MPO, but does not require NETosis.
32471895 Impact of rheumatoid arthritis on major cardiovascular events in patients with and without 2020 Sep INTRODUCTION: Rheumatoid arthritis (RA) is a risk factor for cardiovascular disease. The clinical consequences of coincident RA and coronary artery disease (CAD) are unknown. OBJECTIVE: We aimed to estimate the impact of RA on the risk of adverse cardiovascular events in patients with and without CAD. METHODS: A population-based cohort of patients registered in the Western Denmark Heart Registry, who underwent coronary angiography (CAG) between 2003 and 2016, was stratified according to the presence of RA and CAD. Endpoints were myocardial infarction (MI), major adverse cardiovascular events (MACE; MI, ischaemic stroke and cardiac death) and all-cause mortality. RESULTS: A total of 125 331 patients were included (RA: n=1732). Median follow-up was 5.2 years. Using patients with neither RA nor CAD as reference (cumulative MI incidence 2.7%), the 10-year risk of MI was increased for patients with RA alone (3.8%; adjusted incidence rate ratio (IRR(adj)) 1.63, 95% CI 1.04 to 2.54), for patients with CAD alone (9.9%; IRR(adj) 3.35, 95% CI 3.10 to 3.62), and highest for patients with both RA and CAD (12.2%; IRR(adj) 4.53, 95% CI 3.66 to 5.59). Similar associations were observed for MACE an all-cause mortality. CONCLUSIONS: In patients undergoing CAG, RA is significantly associated with the 10-year risk of MI, MACE and all-cause mortality regardless of the presence of CAD. However, patients with RA and CAD carry the largest risk, while the additive risk of RA in patients without CAD is minor. Among patients with RA, risk stratification by presence or absence of documented CAD may allow for screening and personalised treatment strategies.
32508836 C-Reactive Protein Promotes the Activation of Fibroblast-Like Synoviocytes From Patients W 2020 Objective: To evaluate the biological effect and mechanisms of C-reactive protein (CRP) on the activation of fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA). Study design: To understand if CRP is involved in RA, expression of CRP and its receptors CD32/64 was examined in synovial tissues from RA patients and normal controls. In vitro, the potential role and mechanisms of CRP in FLS proliferation and invasion, expression of pro-inflammatory cytokines, and activation of signaling pathways were investigated in both RA - FLS and a normal human fibroblast-like synoviocyte line (HFLS). Results: Compared to normal controls, synovial tissues from 21 RA patients exhibited highly activated CRP signaling, particularly by FLSs as identified by 65% of CRP-expressing cells being CRP+vimentin+ and CD32/64+vimentin+ cells. In vitro, FLSs from RA patients, but not HFLS, showed highly reactive to CRP by largely increasing proliferative and invasive activities and expressing pro-inflammatory cytokines and chemokines, including CCL2, CXCL8, IL-6, and MMP2/9. All these changes were blocked largely by a neutralizing antibody to CD32 and, to a less extent by the anti-CD64 antibody, revealing CD32 as a primary mechanism of CRP signaling during synovial inflammation. Further studies revealed that CRP also induced synovial inflammation differentially via CD32/CD64- NF-κB or p38 pathways as blockade of CRP-CD32-NF-κB signaling inhibited CXCL8, CCL2, IL-6, whereas CRP induced RA-FLS invasiveness through CD32-p38 and MMP9 expression via the CD64-p38-dependent mechanism. Conclusions: CRP signaling is highly activated in synovial FLSs from patients with RA. CRP can induce synovial inflammation via mechanisms associated with activation of CD32/64-p38 and NF-κB signaling.
33006164 Effects of sinomenine on the proliferation, cytokine production, and regulatory T-cell fre 2021 Apr Sinomenine (SN) is a plant-derived alkaloid isolated from Caulis Sinomenii. It has been approved by the State Food and Drug Administration of China for treating rheumatoid arthritis (RA) nearly 20 years ago. To investigate the anti-RA mechanism of SN, a lot of scholars reported the immunosuppressive effect of SN on T lymphocytes. We continued to evaluate the suppressive function of SN by using human peripheral blood mononuclear cells (PBMCs) isolated from RA patients. As the positive control, 10 ng/ml of methylprednisolone (MP) showed the antiproliferation effect on mitogen-activated PBMCs of RA patients significantly (*p < .05). Meanwhile, MP decreased the frequency of CD4(+) CD25(+) T cells and suppressed the secretion of inflammatory Th1/Th2/Th17 cytokines such as IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α. However, SN at concentrations of 0.3-30 μM, showed little suppressive effects on the proliferation of PBMCs of RA patients. We did not observe any suppressive effects of SN on percentages of CD4(+) T cells and CD4(+) CD25(+) T cells in the mitogen-activated PBMCs of RA patients. The influence of SN on the percentage of CD4(+) CD25(+) Foxp3(+) T cells was also limited. Finally, even 30 μM of SN did not influence the secretion of Th1/Th2/Th17 cytokine significantly. The present study provided evidence that anti-RA mechanism of SN seems not to be related with the suppressive effects on peripheral T cells.
32039051 Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis. 2019 Oral microbial dysbiosis is known to increase susceptibility of an individual to develop rheumatoid arthritis (RA). Individuals at-risk of RA may undergo different phases of disease progression. In this study, we aim to investigate whether and whereby the oral microbiome communities alter prior to symptoms of RA. Seventy-nine saliva samples were collected from 29 high-risk individuals, who were positive for anti-citrullinated protein antibodies (ACPA) and have no clinical arthritis, 27 RA patients and 23 healthy controls (HCs). The salivary microbiome was examined using 16S ribosomal RNA gene sequencing. Alpha and beta diversity analysis and the linear discriminant analysis were applied to examine the bacterial diversity, community structure and discriminatory taxa between three groups, respectively. The correlation between salivary bacteria and autoantibodies were analyzed. In the "pre-clinical" stages, salivary microbial diversity was significantly reduced comparing to RA patients and HCs. In contrast to HCs, like RA patients, individuals at high-risk for RA showed a reduction in the abundance of genus Defluviitaleaceae_UCG-011 and the species Neisseria oralis, but an expansion of Prevotella_6. Unexpectedly, the relative abundance of Porphyromonas gingivalis, reported as opportunistic pathogens for RA development, was significantly decreased in high-risk individuals. Additionally, we identified four genera in the saliva from high-risk individuals positively correlated with serum ACPA titers, and the other two genera inversely displayed. In summary, we observed a characteristic compositional change of salivary microbes in individuals at high-risk for RA, suggesting that oral microbiota dysbiosis occurs in the "pre-clinical" stage of RA and are correlated with systemic autoimmune features.
31421020 Factors Associated With Use of Telemedicine for Follow-up of Rheumatoid Arthritis. 2020 Oct OBJECTIVE: Telemedicine is increasingly being offered to patients for rheumatology care, but few studies have examined factors associated with telemedicine use or outcomes of telemedicine in rheumatology. The objective of this analysis was to determine factors associated with the use of video telemedicine when offered as part of usual care for follow-up of rheumatoid arthritis (RA). METHODS: Individuals in the Alaska Tribal Health System with a diagnosis of RA were recruited when seeing a rheumatologist either in-person or by video telemedicine, both of which were offered as part of usual care. At the study visit, participants completed the Routine Assessment of Patient Index Data 3 (RAPID3) and a telemedicine perception survey and agreed to a medical record review for demographics and disease characteristics. Data from this visit were analyzed to determine factors associated with using telemedicine for RA, compared to being seen in-person only. RESULTS: Of 122 participants enrolled in the study, 56 (46%) had been seen by telemedicine at least once. Factors associated with telemedicine use in univariate analysis included a higher RAPID3 score, a higher number of rheumatologist visits in the preceding year, more positive perceptions of telemedicine, and seeing a physician who used telemedicine more often. On multivariate analysis, these 4 factors all remained significant. Demographic and other disease-related factors or comorbidities were not associated with telemedicine use. CONCLUSION: When offered as an option for rheumatology care, video telemedicine was more likely to be used by RA patients with higher disease activity and more positive perceptions of telemedicine, and by patients whose physicians used telemedicine more often.