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ID PMID Title PublicationDate abstract
32403900 Association of body composition with disease activity and disability in rheumatoid arthrit 2021 Jan BACKGROUND/AIMS: To explore the associations between body composition and pain, disease activity, and disability in rheumatoid arthritis (RA). METHODS: The study enrolled 335 patients with RA and underwent body composition measurement with an InBody analyzer. The associations of body mass index (BMI), body fat mass, and skeletal muscle mass with disease activity score in 28 joints (DAS28), an index derived to measure the subjective component of DAS28 (DAS28-P), a pain visual analogue scale (VAS), and disability measured with the health assessment questionnaire (HAQ) were explored. Obesity was defined as BMI ≥ 25 kg/m2. RESULTS: The median (interquartile range) disease duration was 6 years (3.5 to 9) and the mean DAS28 score was 3.6 ± 1.1. The mean BMI was 23.6 ± 3.6 kg/m2 and 109 patients (32.5%) were obese. Compared with non-obese patients, obese patients had a higher C-reactive protein (1.68 mg/dL vs. < 0.1 mg/dL, p = 0.013), higher pain VAS score (40 vs. 35, p = 0.031), and higher DAS28-erythrocyte sedimentation rate score (3.75 ± 1.18 vs. 3.46 ± 1.11, p = 0.031). In multivariate regression analysis, the DAS28 score in females was positively associated with the current steroid dose, body fat mass, and HAQ score, while the HAQ score in females was associated with older age, DAS28, lower skeletal muscle mass, and higher body fat/skeletal muscle ratio. In the multivariate regression analysis, the DAS28-P score in females was positively associated with body fat/skeletal muscle ratio and HAQ. CONCLUSION: Body composition, such as the body fat mass and body fat/skeletal muscle ratio, is significantly associated with disease activity and disability in female RA patients.
33004534 Tofacitinib Persistence in Patients with Rheumatoid Arthritis: A Retrospective Cohort Stud 2021 Jan 1 OBJECTIVE: To compare medication persistence of tofacitinib with persistence of injectable biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA). METHODS: We performed a retrospective new-user cohort study of patients with RA in the IBM MarketScan Research Databases. New users of tofacitinib or bDMARD were identified between November 2012 and December 2016. Persistence, in number of years, was the time between treatment initiation and the earliest occurrence of discontinuation or switching from the medication prescribed at cohort entry. Persistence of tofacitinib was compared with bDMARD persistence using Cox proportional hazards regression with adjustment for high-dimensional propensity scores. Similar methods were used for an analysis of post first-line therapy in patients who switched to tofacitinib from a bDMARD. RESULTS: New tofacitinib users (n = 1031) were 56 years of age, on average, and 82% were women. New bDMARD users (n = 17,803) were 53 years of age, on average, and 78% were women. New tofacitinib users had shorter medication persistence (median 0.81 yrs) compared to bDMARD patients (1.02 yrs). After adjustment, the HR for discontinuation of tofacitinib compared with bDMARD was 1.14 (95% CI 1.05-1.25). Patients who switched to tofacitinib from a bDMARD had longer persistence than patients who switched to a bDMARD (adjusted HR for discontinuation 0.90, 95% CI 0.83-0.97). CONCLUSION: Further research is warranted to understand the reasons for discontinuation of tofacitinib despite its ease of administration and to understand the observed differences between switchers and new users.
31502378 Immunomodulatory effect of human bone marrow-derived mesenchymal stromal/stem cells on per 2020 Jan Rheumatoid arthritis (RA) is a Th1/Th17-mediated autoimmune disease whose current treatment, consisting in the blockage of inflammatory cytokines by disease-modifying antirheumatic drugs, is not effective for all patients. The therapeutic potential of mesenchymal stromal/stem cells' (MSCs) immunomodulatory properties is being explored in RA. Here, we investigate the effect of human bone marrow (BM)-MSCs on the expression of cytokines involved in RA physiopathology by the distinct functional compartments of CD4(+) and CD8(+) T cells from RA patients. Peripheral blood mononuclear cells from healthy individuals (n = 6) and RA patients (n = 12) were stimulated with phorbol myristate acetate plus ionomycin and cultured in the presence/absence of BM-MSCs. The expression of (interleukin) IL-2, tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) was evaluated in naive, central memory, effector memory, and effector CD4(+) and CD8(+) T cells, whereas IL-6, IL-9, and IL-17 expression was measured in total CD4(+) and CD8(+) T cells. mRNA expression of IL-4, IL-10, transforming growth factor beta (TGF-β), cytotoxic T-lymphocyte-associated antigen 4, and/or forkhead box P3 was quantified in fluorescence-activated cell sorting-purified CD4(+) T cells, CD8(+) T cells, and CD4(+) Treg. BM-MSCs inhibited the production of TNF-α, IL-17, IL-6, IL-2, IFN-γ, and IL-9 by T cells from RA patients, mainly by reducing the percentage of cells producing cytokines. This inhibitory effect was transversal to all T cell subsets analyzed. At mRNA level, BM-MSCs increased expression of IL-10 and TGF-β by CD4(+) and CD8(+) T cells. BM-MSCs displayed a striking inhibitory action over T cells from RA patients, reducing the expression of cytokines involved in RA physiopathology. Remarkably, BM-MSC-derived immunomodulation affected either naive, effector, and memory T cells.
33031288 Herpes Zoster in rheumatoid arthritis patients receiving tofacitinib, a single center expe 2020 Oct 9 In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.
32332540 Revision Carpal Tunnel Release: Risk Factors and Rate of Secondary Surgery. 2020 May BACKGROUND: The first aim of this study was to determine the rate of revision carpal tunnel release in five urban hospitals over a period of 14 years. The secondary aim was to assess what demographic, condition-related, and treatment-related factors are associated with revision carpal tunnel release. METHODS: Between 2002 and 2015, 7464 patients underwent carpal tunnel release. After manually reviewing the medical records, the authors identified 113 patients who underwent revision surgery. Multivariable logistic regression analysis was performed to study association with demographics (age, sex, and race), unilateral or bilateral treated wrist(s) (including carpal tunnel release performed simultaneously and separately), and type of surgery (open or endoscopic). To gain further insight into these factors, a matched case-control analysis in a 1:3 ratio was performed. RESULTS: One hundred thirteen of 7464 patients (1.5 percent) underwent revision carpal tunnel surgery. The median (interquartile range) time to revision surgery was 1.23 years (0.47 to 3.89 years). In multivariable logistic regression analysis, older age, male sex, bilateral carpal tunnel release, and endoscopic carpal tunnel release were independently associated with higher odds for revision surgery. Multivariable conditional logistic regression of the matched case-control cohort showed that smoking and rheumatoid arthritis were independently associated with revision carpal tunnel release. Splint treatment before the initial surgery was independently associated with single carpal tunnel release. CONCLUSION: Endoscopic release, male sex, smoking, rheumatoid arthritis, and undergoing staged or simultaneous bilateral carpal tunnel release are risk factors for revision surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.
33277938 Viral panniculitis in a patient with disseminated opportunistic Enterovirus infection. 2021 Mar Infection-induced panniculitis has been described in association with a broad range of microorganisms. Among those, viral panniculitis represents a minor category, with only a few anecdotal reports in the literature documenting viral infection in the subcutaneous fat. Herein, we report a woman in her 30s with seropositive rheumatoid arthritis on rituximab and prednisone, who presented with a 6-month history of progressive multisystem manifestations, including unintentional weight loss, fever, fatigue, myopathy, pancreatitis, and sensorineural hearing loss. She had indurated plaques on her thighs characterized by predominantly lobular panniculitis with chronic lymphohistiocytic inflammation. Molecular studies performed at the Centers for Disease Control and Prevention identified evidence of Enterovirus group with the highest identity of Coxsackievirus A9. Enterovirus RNA was also detected in the cerebrospinal fluid and muscle. Based on the findings, a diagnosis of disseminated enteroviral infection in the setting of B-cell depletion was rendered. To the best of our knowledge, this represents the first reported case of viral panniculitis with documentation of Coxsackievirus A9 in the skin. Since rituximab may be used for the treatment of autoimmune dermatological diseases, familiarity of the potential occurrence of severe enteroviral infections in the setting of immunosuppressive treatment is important for dermatopathologists.
32151665 Pharmacological targets of metabolism in disease: Opportunities from macrophages. 2020 Jun From advances in the knowledge of the immune system, it is emerging that the specialized functions displayed by macrophages during the course of an immune response are supported by specific and dynamically-connected metabolic programs. The study of immunometabolism is demonstrating that metabolic adaptations play a critical role in modulating inflammation and, conversely, inflammation deeply influences the acquisition of specific metabolic settings.This strict connection has been proven to be crucial for the execution of defined immune functional programs and it is now under investigation with respect to several human disorders, such as diabetes, sepsis, cancer, and autoimmunity. The abnormal remodelling of the metabolic pathways in macrophages is now emerging as both marker of disease and potential target of therapeutic intervention. By focusing on key pathological conditions, namely obesity and diabetes, rheumatoid arthritis, atherosclerosis and cancer, we will review the metabolic targets suitable for therapeutic intervention in macrophages. In addition, we will discuss the major obstacles and challenges related to the development of therapeutic strategies for a pharmacological targeting of macrophage's metabolism.
31530401 The association between gravidity, parity and the risk of developing rheumatoid arthritis: 2020 Apr OBJECTIVE: To establish if gravidity and parity associate with the development of rheumatoid arthritis (RA), and to establish if this effect is influenced by the time elapsed since pregnancy/childbirth, the number of pregnancies/childbirths, and serological status, through systematically reviewing the literature and undertaking a meta-analysis. METHODS: We searched Medline/EMBASE (from 1946 to 2018) using the terms "rheumatoid arthritis.mp" or "arthritis, rheumatoid/" and "pregnancy.mp" or "pregnancy/" or "parity.mp" or "parity/" or "gravidity.mp" or "gravidity/" (observational study filter applied). Case-control/cohort studies that examined the relationship between parity/gravidity and the risk of RA in women were included. Studies reporting effect size data for RA in ever vs. never parous/gravid women as ORs/RRs with 95% confidence intervals were included in a meta-analysis. Other relationships (i.e. risk by pregnancy/childbirth numbers) were analysed descriptively. RESULTS: Twenty studies (from 626 articles) met our inclusion criteria, comprising 14 case-control (4799 cases; 11,941 controls) and 6 cohort studies (8575 cases; 2,368,439 individuals). No significant association was observed in the meta-analysis of studies reporting the risk of RA in ever vs. never parous women (OR 0.91; 95% CI 0.80-1.04) and ever vs. never gravid women (OR 0.86; 95% CI 0.46-1.62). No consistent evidence of a relationship between the number of pregnancies/childbirths and RA risk was seen. No significant association was observed between being pregnant, or in the immediate post-partum period, and the risk of developing RA. CONCLUSION: Our systematic review does not support the concept that gravidity and parity are associated with the risk of RA development.
33526730 EFFICACY OF SPIRONOLACTONE IN ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH RESISTANT HYPERTEN 2020 Dec The aim of the study is to investigate the antihypertensive efficacy, structural and functional remodeling of the heart in patients with resistant hypertension (RH) and rheumatoid arthritis (RA) after 12-month of therapy. The treatment includes angiotensin-converting enzyme inhibitor, calcium channel blocker, diuretics, aldosterone receptor blocker (spironolactone), and immunosuppressive drug (methotrexate). 101 patients with hypertension (H) and RA were examined at the screening visit. 60 patients (mean age 61.9±9.1 years; 84.6% of women) meeting the criteria for RH were selected after 1 month. A randomized, controlled, parallel-group prospective study was conducted. Patients underwent general clinical, laboratory, and Doppler echocardiography investigations. They were divided into 2 groups: the main group, which represented patients whom to the basic antihypertensive therapy were added spironolactone 25 mg/day (group 1, n=30), and the comparison group, which represented patients who continued antihypertensive treatment without the addition of spironolactone (group 2, n=30) with 12- monthly observation. Groups of patients are comparable in age, sex, duration of RA and H, RA activity. The target blood pressure was achieved in 86.7% against 30.0% of patients (p <0.001) on spironolactone treatment compared to the inclusion of it. Therapy with spironolactone shown a probable decrease in the mean systolic blood pressure, diastolic blood pressure, and pulse blood pressure by 11.8%, 17.8%, and 5.4%, respectively. There was a reduction in the number of patients with left atrium dilatation from 86.7% to 63.3% (χ²=4.4, p=0.037) in group 1. The frequency of left ventricular hypertrophy (LVH) dropped by 10% (χ²=3.9, p=0.048) in patients of group 1. The incidence of eccentric LVH with left ventricular (LV) dilatation decreased by 2.2 times, concentric LVH with LV dilatation declined by 2.5 times after treatment in group 1. There was a further LV hypertensive remodeling in group 2: detection of concentric LVH without LV dilatation (χ²=3.3, p=0.04) was increased. There was a reduction of LV mass index (by 13.0%, p<0.01) due to a decrease in the stage of LV dilatation (by 7.3%, p<0.01), and the thickness of its walls (respectively interventricular septum and posterior wall by 17.3% and 15.2%, both p<0.01) in spironolactone group with the absence of probable changes in group 2. The LV contractile capacity, both regional fractional shortening and global ejection fraction improved (decline by 15.5% and 7.9% (both p<0.01)) in group 1 in the absence of dynamics in group 2. The incidence of LV diastolic dysfunction subsided from 83.3% to 40.0% (χ²=11.9, p<0.001) in patients of the spironolactone group, mainly due to a probable lessening in a number of patients with an abnormal LV relaxation from 60.0% to 36.7%. There was a lowering in E/e' med, E/e' lat and E/E' by 8.6%, 6.0% and 7.3%, respectively (all p <0.01) in patients on spironolactone therapy, which reflected the improvement of LV diastolic function. Patients of group 1 demonstrated a de-escalation of RA activity: a dropping of the DAS28-CRP from 5.6 (4.9-6.4) to 4.0 (3.4-5.0) (р<0,0001) in the absence of its dynamics in patients of group 2 (from 5.7 (5.0-6.1) to 5.6 (5.0-6.5) (p=0.6)). The addition of spironolactone to basic therapy demonstrates increased antihypertensive efficacy and potent antihypertrophic efficacy. These effects are combined with improved systolic and diastolic LV function and a decrease of clinical and laboratory activity of RA in elderly patients with RH in combination with RA.
31802210 The effects of exercise on cardiovascular disease risk factors and cardiovascular physiolo 2020 Mar Cardiovascular disease (CVD) morbidity and mortality is highly prevalent in patients with rheumatoid arthritis (RA) with debilitating effects for the individual as well as significant healthcare impact. Current evidence demonstrates that engaging in aerobic and resistance exercise (i.e. structured physical activity) can significantly improve patient-reported and clinical index-assessed outcomes in RA. In addition to this, engagement in exercise programmes improves, in a dose-dependent manner, the risk of developing CVD as well as CVD symptoms and outcomes. The present narrative review uses evidence from systematic reviews and meta-analyses as well as controlled trials, to synthesize the current state-of-the-art on the potential effects of aerobic and resistance exercise on CVD risk factors as well as on cardiac and vascular function and structure in people with RA. Where there is a lack of evidence in RA to explain potential mechanisms, relevant studies from the general population are also discussed and linked to RA.
32152480 NFKB2 polymorphisms associate with the risk of developing rheumatoid arthritis and respons 2020 Mar 9 This study sought to evaluate the association of 28 single nucleotide polymorphisms (SNPs) within NFKB and inflammasome pathway genes with the risk of rheumatoid arthritis (RA) and response to TNF inhibitors (TNFi). We conducted a case-control study in a European population of 1194 RA patients and 1328 healthy controls. The association of potentially interesting markers was validated with data from the DANBIO (695 RA patients and 978 healthy controls) and DREAM (882 RA patients) registries. The meta-analysis of our data with those from the DANBIO registry confirmed that anti-citrullinated protein antibodies (ACPA)-positive subjects carrying the NFKB2(rs11574851T) allele had a significantly increased risk of developing RA (PMeta_ACPA + = 0.0006) whereas no significant effect was found in ACPA-negative individuals (PMeta_ACPA- = 0.35). An ACPA-stratified haplotype analysis including both cohorts (n = 4210) confirmed that ACPA-positive subjects carrying the NFKB2(TT) haplotype had an increased risk of RA (OR = 1.39, P = 0.0042) whereas no effect was found in ACPA-negative subjects (OR = 1.04, P = 0.82). The meta-analysis of our data with those from the DANBIO and DREAM registries also revealed a suggestive association of the NFKB2(rs1056890) SNP with larger changes in DAS28 (OR = 1.18, P = 0.007). Functional experiments showed that peripheral blood mononuclear cells from carriers of the NFKB2(rs1005044C) allele (in LD with the rs1056890, r2 = 1.00) showed increased production of IL10 after stimulation with LPS (P = 0.0026). These results provide first evidence of a role of the NFKB2 locus in modulating the risk of RA in an ACPA-dependent manner and suggest its implication in determining the response to TNFi. Additional studies are now warranted to further validate these findings.
32664585 Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic T 2020 Jul 11 Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.
31821162 Thermography and colour Doppler ultrasound: a potential complementary diagnostic tool in e 2020 May 26 The aim and objectives of this study were as follows: (i) to perform automated segmentation of knee thermal image using the regional isotherm-based segmentation (RIBS) algorithm and segmentation of ultrasound image using the image J software; (ii) to implement the RIBS algorithm using computer-aided diagnostic (CAD) tools for classification of rheumatoid arthritis (RA) patients and normal subjects based on feature extraction values; and (iii) to correlate the extracted thermal imaging features and colour Doppler ultrasound (CDUS) features in the knee region with the biochemical parameters in RA patients. Thermal image analysis based on skin temperature measurement and thermal image segmentation was performed using the RIBS algorithm in the knee region of RA patients and controls. There was an increase in the average skin temperature of 5.94% observed in RA patients compared to normal. CDUS parameters such as perfusion, effusion and colour fraction for the RA patients were found to be 1.2 ± 0.5, 1.8 ± 0.2 and 0.052 ± 0.002, respectively. CDUS measurements were performed and analysed using the image J software. Biochemical parameters such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed significant positive correlation with the thermal imaging parameters. The CDUS parameters such as effusion, perfusion and colour fraction correlated significantly with the clinical and functional assessment score. According to the results of this study, both infrared (IR) thermal imaging and CDUS offer better diagnostic potential in detecting early-stage RA. Therefore, the developed CAD model using thermal imaging could be used as a pre-screening tool to diagnose RA in the knee region.
32964298 Comparison of the analytical and clinical performances of four anti-cyclic citrullinated p 2021 Feb INTRODUCTION/OBJECTIVES: Anti-cyclic citrullinated peptide antibody (anti-CCP) is one of the most important serologic markers for diagnosing rheumatoid arthritis (RA). This study aimed to compare the analytical and clinical performances of the second- and third-generation anti-CCP assays. METHODS: Four automated anti-CCP assays were evaluated: Chorus anti-CCP (Diesse Diagnostica), Elecsys anti-CCP (Roche Diagnostics), Atellica® IM anti-CCP IgG (Siemens Healthineers), and Quanta Flash® CCP3 (Inova Diagnostics Inc.). Analytical performance included the precision, linearity, correlation, and concordance rate. For evaluating the clinical performance, 240 patient samples (120 positive and 120 negative samples, determined by the Chorus anti-CCP assay) were used, including those with a diagnosis of RA (n = 132) and non-RA (n = 108). Using receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity were evaluated. RESULTS: All four assays that were evaluated showed good precision and linearity, and their correlation and concordance rates were in acceptable ranges. The area under the curve (AUC) values ranged from 0.888 to 0.914, showing a good diagnostic performance. The sensitivity and specificity of all assays were similar (88.0-97.2%). CONCLUSIONS: All four anti-CCP assays showed good analytical and diagnostic performances for diagnosing RA. After adjusting the cutoff values, these assays are expected to show enhanced sensitivity and specificity. Key Points • Previous studies have described the diagnostic performance of a few immunologic markers in RA diagnosis, but nothing has been proven to be sufficiently good in clinical practice. • All four automated anti-CCP assays showed good analytical and diagnostic performances for diagnosing RA in clinical practice. • After adjusting the cutoff values, these assays are expected to show enhanced sensitivity and specificity. • The present study provides reassuring evidence that any of the studied commercially available anti-CCP tests for detecting rheumatoid arthritis provide similar diagnostic information to institutions that adopt these specific testing systems.
33270017 BAD inactivation exacerbates rheumatoid arthritis pathology by promoting survival of subli 2020 Dec 3 The resistance of synovial sublining macrophages to apoptosis has a crucial role in joint inflammation and destruction in rheumatoid arthritis (RA). However, the underlying mechanism is incompletely understood. Here we report that inactivation of the pro-apoptotic BCL-2 family protein BAD is essential for survival of synovial sublining macrophage in RA. Genetic disruption of Bad leads to more severe joint inflammation and cartilage and bone damage with reduced apoptosis of synovial sublining macrophages in collagen-induced arthritis (CIA) and TNFα transgenic (TNF-Tg) mouse models. Conversely, Bad(3SA/3SA) mice, in which BAD can no longer be inactivated by phosphorylation, are protected from collagen-induced arthritis. Mechanistically, phosphorylation-mediated inactivation of BAD specifically protects synovial sublining macrophages from apoptosis in highly inflammatory environment of arthritic joints in CIA and TNF-Tg mice, and in patients with RA, thereby contributing to RA pathology. Our findings put forward a model in which inactivation of BAD confers the apoptosis resistance on synovial sublining macrophages, thereby contributing to the development of arthritis, suggesting that BAD may be a potential therapeutic target for RA.
31907043 Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding 2020 Jan 6 BACKGROUND: Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls. METHODS: In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC-MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90). RESULTS: We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. CONCLUSIONS: This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.
31585899 T-96 attenuates inflammation by inhibiting NF-κB in adjuvant-induced arthritis. 2020 Jan 1 The extract of the medicinal plant, Tripterygium wilfordii Hook. f. (TW), has been used in the treatment of diverse autoimmune diseases, including rheumatoid arthritis. However, the high frequency of toxic side effects has limited its clinical use. In order to reduce toxicity without losing the therapeutic benefit, the pharmacological activity and toxicity of four compounds (T-96, triptolide, neotripterifordin, and tripterifordin) from TW were evaluated. The current study revealed that these compounds interfere with the IL-1β signaling pathway, which stimulates the secretion of pro-inflammatory cytokines (IL-6) in primary rheumatoid arthritis synovial fibroblasts (RASFs). These compounds inhibit IL-6 production, and among these, T-96 was the most effective. Moreover, T-96 blocks activation of NF-kappa B and p38 and ameliorates the joint destruction and the clinical signs of the disease in adjuvant-induced arthritic rats. These data suggest that among the four compounds of the TW, T-96 possesses highest anti-rheumatoid arthritis activity though inhibiting IL-1-mediated inflammatory signaling pathways.
31883829 Histone deacetylase 1 (HDAC1): A key player of T cell-mediated arthritis. 2020 Mar Rheumatoid Arthritis (RA) represents a chronic T cell-mediated inflammatory autoimmune disease. Studies have shown that epigenetic mechanisms contribute to the pathogenesis of RA. Histone deacetylases (HDACs) represent one important group of epigenetic regulators. However, the role of individual HDAC members for the pathogenesis of arthritis is still unknown. In this study we demonstrate that mice with a T cell-specific deletion of HDAC1 (HDAC1-cKO) are resistant to the development of Collagen-induced arthritis (CIA), whereas the antibody response to collagen type II was undisturbed, indicating an unaltered T cell-mediated B cell activation. The inflammatory cytokines IL-17 and IL-6 were significantly decreased in sera of HDAC1-cKO mice. IL-6 treated HDAC1-deficient CD4(+) T cells showed an impaired upregulation of CCR6. Selective inhibition of class I HDACs with the HDAC inhibitor MS-275 under Th17-skewing conditions inhibited the upregulation of chemokine receptor 6 (CCR6) in mouse and human CD4(+) T cells. Accordingly, analysis of human RNA-sequencing (RNA-seq) data and histological analysis of synovial tissue samples from human RA patients revealed the existence of CD4(+)CCR6(+) cells with enhanced HDAC1 expression. Our data indicate a key role for HDAC1 for the pathogenesis of CIA and suggest that HDAC1 and other class I HDACs might be promising targets of selective HDAC inhibitors (HDACi) for the treatment of RA.
31577214 Incidence and predictors of adverse clinical events in patients with rheumatoid arthritis 2020 May OBJECTIVES: Patients with rheumatoid arthritis (RA) are exposed to impairment in left ventricular (LV) function, which is a prognosticator of poorer clinical outcomes. In this study we assessed prevalence and factors associated with adverse outcomes in patients with RA and asymptomatic LV systolic dysfunction (LVSD). METHODS: We prospectively analysed 102 RA patients with asymptomatic LVSD consecutively selected by a pool of 418 RA patients referred to the Division of Rheumatology, University of Verona, between March 2014 and March 2015. LVSD was defined as impaired global longitudinal strain (GLS) measured by echocardiography. The pre-specified study end-points were all-cause death/hospitalisation, and death/hospitalisation for cardiovascular cause. RESULTS: During a follow-up of 35 [13-54] months, all-cause death/hospitalisation occurred in 40 patients (39%). No patient died during the follow-up, 18 patients (18% of the study population) had a cardiovascular event which required hospitalisation, while 22 (22% of patients) required hospitalisation, but this was unrelated to CV. Multiple Cox regression analysis identified worse renal function, more frequent use and a higher number of biologic DMARDs used before enrolment as independent predictors of all-causes hospitalisation. The same variables together with higher LV mass predicted CV hospitalisation. Prognostic cut-off points were 90 ml/min/1.73 m2 for glomerular filtration rate and 49 g/m2.7 for LV mass. CONCLUSIONS: RA patients with asymptomatic LVSD have a very high rate of all-cause and cardiovascular hospitalisation at mid-term follow-up, predicted by worse renal function, higher LV mass, more frequent use and higher number of biologic DMARDs used before enrolment, suggesting that biologic DMARDs refractory is a proxy of adverse events.
32441383 Impact of persistence with tumour necrosis factor inhibitors on healthcare resource utiliz 2021 Jan AIM: To assess persistence with subcutaneous (SC) tumour necrosis factor (TNF) inhibitors as well as the impact of persistence on healthcare resource utilization (HCRU) and costs in patients with chronic inflammatory joint diseases. METHODS: In this cohort study using population-based French claims data (from 2011 to 2014), we measured persistence with SC TNF inhibitors within 12 months (M0-12) following treatment initiation in treatment-naïve and treatment-experienced users (divided into three cohorts: rheumatoid arthritis [RA], ankylosing spondylitis [AS] and psoriatic arthritis [PsA]). Persistent patients were propensity score matched to nonpersistent patients at M12. The impact of persistence status on HCRU and costs was assessed during M12-24. RESULTS: Of treatment-naïve (n = 3,804) and treatment-experienced (n = 2,279) users, only 56.1% and 46.8% were persistent at M12, respectively. Nonpersistent patients had more outpatient visits, computerized tomography scans, spine or joint magnetic resonance imaging procedures and disease-related hospitalizations, while persistent patients had more rheumatologist visits. Nonpersistent patients had lower drug costs but higher nondrug-related healthcare and hospitalization costs than persistent patients. In AS and PsA, overall healthcare costs were similar in persistent and nonpersistent patients. In RA, overall healthcare costs were lower in persistent patients (15,753€ vs 17,590€ in treatment-naïve and 17,622€ vs 21,177€ in treatment-experienced). CONCLUSION: Persistence with SC TNF inhibitors within first 12 months following treatment initiation was low in both treatment-naïve and treatment-experienced patients. Differences were observed in distribution of costs between persistent and nonpersistent patients, showing that nonpersistence with SC TNF inhibitors can lead to increased HCRU and higher costs.