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ID PMID Title PublicationDate abstract
31906244 Co-Expression Profile of TNF Membrane-Bound Receptors Type 1 and 2 in Rheumatoid Arthritis 2019 Dec 31 INTRODUCTION: Tumor necrosis factor (TNFα) is an important proinflammatory cytokine in rheumatoid arthritis (RA) immune processes. However, TNFα activity and functions may be regulated by soluble receptors, which act as decoys, and by number, density, and co-expression of its membrane-bound receptors type 1 and 2 (TNFR1 and TNFR2). The aim of this study was to reveal associations between TNFR1/2 co-expression profile parameters and RA disease activity indicators. METHODS: PBMC were analyzed from 46 healthy donors and 64 patients with RA using flow cytometry. Patients were divided according to the disease activity score (DAS) 28 index into groups with high (n = 22, 34.4%), moderate (n = 30, 46.9%), and low (n = 12, 18.8%) disease activity. Co-expression of TNFR1 and TNFR2 was studied by evaluating the percentage of cells, with different receptors, and by counting the number of receptors of each type per cell, using QuantiBritePE beads. Associations between disease severity and activity indicators and parameters of TNFα receptor expression in subpopulations of immune cells were studied. RESULTS: T cell subsets from RA patients were characterized by co-expression of TNFR1 and TNFR2, and were found to differ significantly compared with healthy donors. Memory cells both among T helper cells and cytotoxic T cells demonstrated the most significant differences in TNFR-expression profile. Multivariable logistic regression revealed model to identified RA patients from healthy individual based on the TNFR1/2 co-expression parameters. CONCLUSION: The profile of TNFR12 co-expression differs in RA comparing with health. Proportion of TNFR1+TNFR2- cells increased significantly among memory T helper cells and activated cytotoxic T cells, and decreased significantly among naïve cytotoxic T cells and T regulatory cells as compared with health. The parameters of TNFR12 co-expression in RA are associated with clinical and laboratory indicators of disease activity.
30856539 Sinomenine mitigates collagen-induced arthritis mice by inhibiting angiogenesis. 2019 May OBJECTIVE: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. METHODS: Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD). RESULTS: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1α, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups. CONCLUSION: SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1α-VEGF-ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis.
31694669 DESE: estimating driver tissues by selective expression of genes associated with complex d 2019 Nov 6 The driver tissues or cell types in which susceptibility genes initiate diseases remain elusive. We develop a unified framework to detect the causal tissues of complex diseases or traits according to selective expression of disease-associated genes in genome-wide association studies (GWASs). This framework consists of three components which run iteratively to produce a converged prioritization list of driver tissues. Additionally, this framework also outputs a list of prioritized genes as a byproduct. We apply the framework to six representative complex diseases or traits with GWAS summary statistics, which leads to the estimation of the lung as an associated tissue of rheumatoid arthritis.
31786989 Outcomes following total elbow arthroplasty for rheumatoid arthritis versus post-traumatic 2019 Dec AIMS: The aim of this meta-analysis was to compare the outcome of total elbow arthroplasty (TEA) undertaken for rheumatoid arthritis (RA) with TEA performed for post-traumatic conditions with regard to implant failure, functional outcome, and perioperative complications. MATERIALS AND METHODS: We completed a comprehensive literature search on PubMed, Web of Science, Embase, and the Cochrane Library and conducted a systematic review and meta-analysis. Nine cohort studies investigated the outcome of TEA between RA and post-traumatic conditions. The preferred reporting items for systematic reviews and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)) guidelines and Newcastle-Ottawa scale were applied to assess the quality of the included studies. We assessed three major outcome domains: implant failures (including aseptic loosening, septic loosening, bushing wear, axle failure, component disassembly, or component fracture); functional outcomes (including arc of range of movement, Mayo Elbow Performance Score (MEPS), and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire), and perioperative complications (including deep infection, intraoperative fracture, postoperative fracture, and ulnar neuropathy). RESULTS: This study included a total of 679 TEAs for RA (n = 482) or post-traumatic conditions (n = 197). After exclusion, all of the TEAs included in this meta-analysis were cemented with linked components. Our analysis demonstrated that the RA group was associated with a higher risk of septic loosening after TEA (odds ratio (OR) 3.96, 95% confidence interval (CI) 1.11 to 14.12), while there was an increased risk of bushing wear, axle failure, component disassembly, or component fracture in the post-traumatic group (OR 4.72, 95% CI 2.37 to 9.35). A higher MEPS (standardized mean difference 0.634, 95% CI 0.379 to 0.890) was found in the RA group. There were no significant differences in arc of range of movement, DASH questionnaire, and risk of aseptic loosening, deep infection, perioperative fracture, or ulnar neuropathy. CONCLUSION: The aetiology of TEA surgery appears to have an impact on the outcome in terms of specific modes of implant failures. RA patients might have a better functional outcome after TEA surgery. Cite this article: Bone Joint J 2019;101-B:1489-1497.
31347786 Early restoration of immune and vascular phenotypes in systemic lupus erythematosus and rh 2019 Sep This translational multi-centre study explored early changes in serologic variables following B lymphocyte depletion by rituximab (RTX) treatment in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients and investigated in vitro effects on the activity of other immune cells and the vascular endothelium. Eighty-five SLE patients, seventy-five RA patients and ninety healthy donors were enrolled. Two additional cohorts of selected SLE and RA patients were treated with RTX for 3 months. Changes in circulating levels of inflammatory mediators, oxidative stress markers and NETosis-derived bioproducts were evaluated. Serum miRNomes were identified by next-generation sequencing, and RTX-induced changes were delineated. Mechanistic in vitro studies were performed to assess activity profiles. Altered inflammatory, oxidative and NETosis-derived biomolecules were found in SLE and RA patients, closely interconnected and associated to specific miRNA profiles. RTX treatment reduced SLE and RA patients' disease activity, linked to a prominent alteration in those biomolecules and the reversal of altered regulating miRNAs. In vitro studies showed inhibition of NETosis and decline of pro-inflammatory profiles of leucocytes and human umbilical vein endothelial cells (HUVECs) after B cell depletion. This study provides evidence supporting an early RTX-induced re-setting of the pro-inflammatory status in SLE and RA, involving a re-establishment of the homeostatic equilibrium in immune system and the vascular wall.
31662322 Unmet need in rheumatology: reports from the Targeted Therapies meeting 2019. 2020 Jan OBJECTIVES: To detail the greatest areas of unmet scientific and clinical needs in rheumatology. METHODS: The 21st annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. During the meeting, breakout sessions were convened, consisting of 5 disease-specific groups with 20-30 experts assigned to each group based on expertise. Specific groups included: rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and other systemic autoimmune rheumatic diseases. In each group, experts were asked to identify unmet clinical and translational research needs in general and then to prioritise and detail the most important specific needs within each disease area. RESULTS: Overarching themes across all disease states included the need to innovate clinical trial design with emphasis on studying patients with refractory disease, the development of trials that take into account disease endotypes and patients with overlapping inflammatory diseases, the need to better understand the prevalence and incidence of inflammatory diseases in developing regions of the world and ultimately to develop therapies that can cure inflammatory autoimmune diseases. CONCLUSIONS: Unmet needs for new therapies and trial designs, particularly for those with treatment refractory disease, remain a top priority in rheumatology.
31439624 An Accord of Nuclear Receptor Expression in CD4(+) T Cells in Rheumatoid Arthritis. 2019 Aug 22 Chronically activated CD4(+) T cells drive uncontrolled inflammation, leading to tissue damage in various autoimmune disorders, such as rheumatoid arthritis (RA). Investigation of the molecular mechanisms involved in RA and recent analysis of transcriptomic profiles has implicated members of the nuclear receptor (NR) superfamily in RA. NRs are required for the development, differentiation, and effector function of CD4(+) T cells; therefore, it is thought that NRs are important in shaping the CD4(+) T cell repertoire and associated inflammation in RA. Despite their relevance, the full potential of the NR superfamily in RA, either as biomarkers or disease targets, has not been harnessed. To gain insight on the NR members that are closely associated with RA disease activity, we generated an expression atlas for the NR superfamily in CD4(+) T cells isolated either in a steady state or over the course of collagen-induced arthritis mouse model of RA. We observed discrete expression patterns among the NR superfamily during the disease stages. NRs that instigate anti-inflammatory programs underwent major downregulation during disease onset; however, during the fully developed disease stage we noticed that NRs that induce proinflammatory programs had reduced transcript levels. These animal findings corroborated well with the expression patterns of NRs in clinical samples obtained from RA patients. Furthermore, we observed that targeting NRs using synthetic ligands alleviates the progression of collagen-induced arthritis. Overall, our data demonstrates the potential of the NR superfamily as novel therapeutic targets for the treatment of autoimmune disorders.
31573477 "There is something you must see": breaking down the remission concept in rheumatoid arthr 2020 Jan OBJECTIVES: To explore the remission concept in rheumatoid arthritis (RA) and the implications of the existing definitions when applied to clinical practice among rheumatologists with different profiles. METHODS: A qualitative study through focus groups was conducted. Three focus groups were organised from February to March 2016. Each group was composed of rheumatologists with extensive clinical experience with different profiles; experts in basic research (RBR), experts in imaging techniques research (RIR), and experts in clinical research (RCR). The data was collected with audio recording. Verbatim transcriptions of the audio files were made, and a subsequent reflexive thematic analysis assisted by ATLAS.ti (GmbH, Berlin, v. 7) software was performed. RESULTS: From the reflexive thematic analysis, three main themes were generated: (1) remission limitations, (2) instruments or measures to assess remission, and (3) a new definition of remission. Rheumatologists mentioned frequently that the following variables should be considered when developing a new remission definition: inflammatory activity, calprotectin, psychological variables, sex, disease stage, and sociocultural factors. Contrary to what could be expected, all groups acknowledged that their research field could contribute with domains for a gold standard remission instrument, but not in a hierarchical arrangement of importance. The dissonance existing in the entire remission evaluation process was outlined: remission in clinical practice versus remission in clinical trials, remission following the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean versus Musculoskeletal Ultrasound (US) remission, and remission from the rheumatologist's point of view versus the patient's point of view. CONCLUSIONS: Currently, rheumatologists would not accept a domain as more important than others in remission. Our suggestion is, not to generate a universal definition of remission - one that could cover all aspects - but rather to develop definitions of remission for the different settings that could be pondered by the patient's perspective.
30168259 Clinical utility of red blood cell distribution width in inflammatory and non-inflammatory 2019 Jan AIM: Current studies demonstrate red blood cell distribution width (RDW) as a possible surrogate biomarker of inflammation. The objectives of the present study were to examine RDW in patients with osteoarthritis (OA), fibromyalgia (FM), rheumatoid arthritis (RA) and spondyloarthritis (SpA) and to evaluate its clinical importance. METHODS: Six hundred and ninety-nine ambulatory patients were evaluated. RDW, hemoglobin, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed. In order to compare groups, a Kruskall-Wallis test with post hoc Dunn's test was applied. A multiple logistic regression analysis was used to evaluate anisocytosis explanatory variables. RESULTS: Red blood cell distribution width values differed significantly among groups. Post hoc analysis demonstrated a significant increase in RDW within RA versus OA groups (P < 0.001), active SpA versus OA (P < 0.001), RA versus FM (P < 0.001) and active SpA versus FM groups (P = 0.001). Presence of anisocytosis was useful to discriminate between active articular inflammatory versus non-inflammatory diseases with 48-95% sensitivity and 66-95% specificity. Multivariate analysis showed a six-fold increase in anisocytosis for the presence of a possible articular inflammatory disease. CONCLUSION: In subjects with articular pain, RDW interpretation is a useful tool in clinical practice to distinguish between articular inflammatory and non-inflammatory joint diseases, as with CRP. RDW seems to be a surrogate marker of the inflammatory process.
31791386 Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 2019 Dec 2 BACKGROUND: Patient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR). METHODS: PRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated. RESULTS: In 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients. CONCLUSIONS: In bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.
30077546 Elevated levels of IL-37 correlate with T cell activation status in rheumatoid arthritis p 2019 Jan OBJECTIVE: To assess the association between serum levels of IL-37 in rheumatoid arthritis patients and percentage of peripheral blood T lymphocytes expressing the activation marker CD26 and investigate their correlation with disease activity. METHODS: The study included 48 rheumatoid arthritis patients and 42 age and sex matched healthy controls. Serum levels of IL-37 were determined using enzyme linked immunosorbent assay while percentage of CD3(+)CD26(+)T cells in peripheral blood mononuclear cells was assayed using flowcytometry. RESULTS: Serum levels of IL-37, as well as the percentage of CD3(+)CD26(+)T cells, were significantly higher in rheumatoid arthritis patients than in healthy controls. Also, serum IL-37 levels were higher in patients with severe disease activity than patients with moderate and low disease activity. In rheumatoid arthritis patients, both serum levels of IL-37 and percentage of CD3(+)CD26(+)T cells correlated with disease activity (DAS28), C-reactive protein levels and erythrocyte sedimentation rate. In addition, serum levels of the anti-inflammatory cytokine IL-37 positively correlated with the percentage of CD3(+)CD26(+)T cells in peripheral blood of rheumatoid arthritis patients. CONCLUSION: Our results indicate a strong correlation between serum levels of IL-37 and frequency of activated T cells in peripheral blood of rheumatoid arthritis patients. Our results suggest that in an active disease status, activated T lymphocytes may be a contributing source to the elevated levels of IL-37 trying to down-regulate the active inflammatory process.
31800112 Effect of systemic lupus erythematosus and rheumatoid arthritis on sudden sensorineural he 2020 Oct OBJECTIVES: Recent reports have identified autoimmune systemic diseases as a significant risk factor for sudden sensorineural hearing loss (SSNHL). We investigated whether systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were correlated with the hearing recovery of SSNHL. STUDY DESIGN: A retrospective study. METHODS: Records of 663 SSNHL patients between January 2008 and January 2019 were retrospectively reviewed, including demographic, comorbid diseases, and hearing recovery. Patients were divided into four groups (complete, partial, slight, and no recovery) according to Siegel's criteria and Chinese Medical Association of Otolaryngology (CMAO) criteria. Multinomial logistic regression was performed to evaluate the effects of onset of treatment, initial hearing threshold, audiogram pattern, diabetes mellitus, SLE, and RA on the prognosis of SSNHL according to both criteria. RESULTS: Patients in complete recovery, partial recovery, slight recovery, and no improvement were 95 (14.3%), 183 (27.6%), 170 (25.6%), and 215 (32.4%) by Siegel's criteria, and 90 (13.6%), 152 (22.9%), 188 (28.4%), and 233 (35.1%) by CMAO criteria, respectively. Among the four groups, onset of treatment, initial hearing threshold, diabetes mellitus, SLE, RA, and profound audiogram pattern were found to be associated with recovery outcome by both Siegel's criteria and CMAO criteria (P < .05). According to analysis results, presence of SLE, RA, diabetes mellitus and higher initial hearing threshold were significantly correlated with a poor prognosis by both Siegel's criteria and CMAO criteria (P < .05). CONCLUSION: Comorbid SLE or RA may negatively affect the prognosis of SSNHL. Lower initial hearing threshold and absence of diabetes mellitus are associated with favorable hearing recovery. LEVEL OF EVIDENCE: 4. Laryngoscope, 130:2475-2480, 2020.
31605071 Gums and joints: is there a connection? Part one: epidemiological and clinical links. 2019 Oct Rheumatoid arthritis (RA) and chronic periodontitis are common chronic inflammatory diseases that share numerous clinical and pathobiological characteristics. Due to their similarities, despite manifesting at anatomically distinct sites, the relationship between these two diseases has been investigated for many years. This review attempts to summarise the state of the field based on evidence published in the last ten years.
30813823 First line of biological drugs in rheumatoid arthritis: a medication persistence analysis. 2019 Apr OBJECTIVES: To evaluate the persistence of biological drugs used as the first line of biological treatment in patients diagnosed with rheumatoid arthritis. The predictors associated with persistence have also been verified. METHODS: We evaluated a historical cohort composed of users of the Brazilian National Health System in the period between 2006 January and 2014 December. The endpoint was the medication persistence at 12 months. RESULTS: A population composed of 66,787 individuals started the first line of biological drug. Out of such individuals, 34,595 (51.80%) persisted in the treatment at 12 months. Abatacept was the drug that presented higher persistence, followed by golimumab, tocilizumab, etanercept, and adalimumab and, with lower persistence certolizumab and infliximab. Younger individuals, living in regions with higher social inequality by Gini coefficient, using certolizumab and infliximab in comparison with adalimumab presented a higher risk of non-persistence to treatment. Individuals from the Southeastern region were more persistent than Northeastern, Central-western, Northern and Southern regions. CONCLUSION: The medication persistence was different between biological drugs. The rigorous follow-up of patients, by a multidisciplinary team, is important to enable the development of strategies for the adequate use of such drugs.
31691041 Prevalence and risk factors associated with vertebral osteoporotic fractures in patients w 2020 Feb OBJECTIVES: To explore the prevalence and risk factors of osteoporosis (OP) and vertebral osteoporotic fracture (VOPF) in patients with rheumatoid arthritis (RA). METHODS: Anteroposterior and lateral X-ray examination of the vertebral column (T4-L4) was used for the semi-quantitative assessment of VOPF. Bone mineral density was measured by dual-energy X-ray absorptiometry. RESULTS: Of 865 RA patients, the prevalence of OP and VOPF was 33.6% and 20.2%, respectively. Patients with OP or VOPF were older, and had longer term use and a larger daily amount and cumulative dose of glucocorticoids (GCs), longer disease duration, and higher Health Assessment Questionnaire (HAQ) scores and Sharp scores than patients without OP or VOPF (P < 0.05). OP was also correlated with higher disease activity. The patients treated with GCs had higher incidences of OP and VOPF than the patients without GCs (P < 0.05). The cutoff values in the area under curve (AUC) of the daily dose or treatment course of GCs-VOPF were 9 mg and 37.5 days. Older age, female sex, and a higher Sharp score were risk factors for OP in RA patients, while higher BMI was a protective factor. Older age and a high GC daily dose were risk factors for VOPF in RA patients. CONCLUSIONS: RA patients have a high prevalence of OP and VOPF. Older age, female sex, lower BMI, and higher activity and severity of RA are closely related with OP. Older age and a higher GC daily dose are risk factors for VOPF in RA patients. Key Points • Older age, female sex, lower BMI, and a higher Sharp score were risk factors for OP in RA patients. • Older age and a high GC daily dose were risk factors for VOPF in RA patients. • OP and VOPF in RA patients were correlated with longer disease duration and higher severity of RA.
31076942 Influence of different supplementation on platelet aggregation in patients with rheumatoid 2019 Sep INTRODUCTION: Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have been reported to reduce platelet aggregation. Our aim was to prospectively assess the potential influence of different supplementation omega-3 PUFA on the antiplatelet effects in rheumatoid arthritis (RA) patients. METHODS: The study included 60 patients with RA at the Department of Rheumatology, Clinical Center Kragujevac. Patients were divided into three groups depending on who used concentrated fish oil only or concentrated fish oil in combination with evening primrose oil or control group without supplementation in a period of 3 months. Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test, aranchidonic acid-induced aggregation (ASPI) test, thrombin receptor-activating peptide (TRAP) test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP representing the degree of inhibition of platelet aggregation compared to the basal value. The platelet function analysis in whole blood was performed 18-24 h before starting supplementation and after 90 days. Considerations were taken in the representation of demographic, clinical characteristics, and laboratory parameters between the groups. RESULTS: Patients who used concentrated fish oil only had a significantly lower value of the ratio of ADP/TRAP (0.68 ± 0.20) compared to patients without supplementation (0.83 ± 0.12; p = 0.008), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. CONCLUSIONS: Co-administration of supplementation-concentrated fish oil may reduce platelet aggregation in adults with RA. KEY POINTS: • Omega-3 PUFAs are essential for health and are known to possess anti-inflammatory properties, improving cardiovascular health as well as benefiting inflammatory diseases.. • In this paper, we report on anti-aggregation effects n-3 PUFAs and ɤ-linolenic acid in RA. • The risk of cardiovascular morbidity and mortality is increased in RA, and dietary supplementation of n-3 PUFA may have preventive potential for the cardiovascular management in rheumatoid arthritis.
30718722 Autoimmune rheumatic disease IgG has differential effects upon neutrophil integrin activat 2019 Feb 4 The importance of neutrophils in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), is increasingly recognised. Generation of reactive oxygen species (ROS) and release of neutrophil extracellular traps (NETs) by activated neutrophils are both thought to contribute to pathology; although the underlying mechanisms, particularly the effects of IgG autoantibodies upon neutrophil function, are not fully understood. Therefore, we determined whether purified IgG from patients with SLE or RA have differential effects upon neutrophil activation and function. We found that SLE- and RA-IgG both bound human neutrophils but differentially regulated neutrophil function. RA- and SLE-IgG both increased PMA-induced β(1) integrin-mediated adhesion to fibronectin, whilst only SLE-IgG enhanced α(M)β(2) integrin-mediated adhesion to fibrinogen. Interestingly, only SLE-IgG modulated neutrophil adhesion to endothelial cells. Both SLE- and RA-IgG increased ROS generation and DNA externalisation by unstimulated neutrophils. Only SLE-IgG however, drove DNA externalisation following neutrophil activation. Co-culture of neutrophils with resting endothelium prevented IgG-mediated increase of extracellular DNA, but this inhibition was overcome for SLE-IgG when the endothelium was stimulated with TNF-α. This differential pattern of neutrophil activation has implications for understanding SLE and RA pathogenesis and may highlight avenues for development of novel therapeutic strategies.
31486859 [Role of janus kinase inhibitors in the treatment of rheumatic diseases]. 2019 Nov Janus kinases inhibitors (JAKI) are new orally administrable disease-modifying antirheumatic drugs (DMARD) for the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), representing a treatment alternative equally effective as biological DMARD that is also classified equivalent in the guidelines. JAKI reversibly inhibit intracellular signal transduction from the cytokine receptor to the nucleus. Tofacitinib and baricitinib, two JAKI already approved for RA treatment, are taken once or twice a day, respectively, and two more are expected to receive approval next year. Tofacitinib is also approved for PsA. Generally, JAKI are initially used in combination with methotrexate (MTX) but are equally effective as monotherapeutic treatment if MTX is contraindicated. In terms of therapy safety, JAKI and bDMARD are generally comparable with one exception: JAKI are associated with an increased risk of herpes zoster infection. JAKI treatment requires laboratory blood tests, especially blood count, transaminases and creatinine. Due to hepatic metabolization, tofacitinib is associated with certain drug interactions. Altogether JAKI enhance treatment possibilities for diseases such as RA and PsA combining the same effectiveness and safety as bDMARD with the option of oral administration.
30951267 Patient-Reported Outcome Data From an Early Rheumatoid Arthritis Trial: Opportunities for 2019 Dec OBJECTIVE: Treating early, intensively, and to target leads to rapid disease control, preventing joint damage and loss of function in early rheumatoid arthritis (RA). We report the effect of such an approach on patient-reported outcomes and explore the contribution of rapid and persistent disease control to well-being after 1 year of treatment. METHODS: This study is part of the Care in Early RA trial, a prospective, 2-year, investigator-initiated, randomized controlled trial rooted in daily practice and implementing the treat-to-target principle. Short Form 36 (SF-36) health survey and Revised Illness Perception Questionnaire (IPQ-R) data were collected prospectively. We defined 4 clinical response profiles based on speed and consistency of the treatment response within the first year, defined as the Disease Activity Score in 28 joints using the C-reactive protein level <2.6. Linear regression analyses including these response profiles and treatment type were constructed to predict the SF-36 dimensions of vitality, social functioning, role emotional, and mental health, and the IPQ-R illness perception subscales of consequences, treatment control, and illness coherence at year 1. RESULTS: A total of 333 patients were available for the main analyses, including 140 early persistent responders. Variation in each of the psychosocial outcomes at year 1 was explained mostly by baseline values, followed by the clinical response profiles. Patients with an early persistent response reported significantly higher vitality, more positive beliefs about disease consequences and treatment effect. Treatment type did not matter. CONCLUSION: Rapid and persistent disease control and not treatment type were associated with favorable patient-reported health and illness perceptions at year 1, but baseline psychosocial variables mattered most. Our data indicate opportunities to broaden the scope of the treat-to-target principle in early RA.
31401905 Effect of Interleukin-34 on Secretion of Angiogenesis Cytokines by Peripheral Blood Mononu 2020 Feb BACKGROUND: Interleukin (IL)-34 is a new pro-inflammatory cytokine. Previous studies showed that IL-34 plays a key role in inflammation and osteoporosis in rheumatoid arthritis (RA). However, whether IL-34 participates in angiogenesis in RA remains unknown. Vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) play critical roles in the angiogenesis of RA. METHODS: 22 patients with RA, 18 patients with ankylosing spondylitis (AS), and 8 healthy subjects were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were isolated and purified from peripheral blood by density gradient centrifugation. PBMCs were stimulated using anti-CD3/CD28 antibody and different concentrations of recombinant human (rh) IL-34 (0, 10, 20, 50, 100 ng/mL). Cell-free supernatants were collected after 72 h incubation, and VEGF and HIF-1α levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-34 promotes the secretion of VEGF and HIF-1α by PBMCs in RA patients in a dose-dependent manner. In contrast, IL-34 has no effect on VEGF and HIF-1α secretion by PBMCs in AS and healthy controls. CONCLUSION: IL-34 may indirectly contribute to angiogenesis by promoting the production of VEGF and HIF-1α and participate in the pathogenesis of RA.