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ID PMID Title PublicationDate abstract
28962590 A somatization comorbidity phenotype impacts response to therapy in rheumatoid arthritis: 2017 Sep 29 BACKGROUND: Comorbidities may contribute to disease activity and treatment response in rheumatoid arthritis (RA) patients. We defined a somatization comorbidity phenotype (SCP) and examined its influence on response to certolizumab pegol (CZP) using data from the PREDICT trial. METHODS: Patients in PREDICT were randomized to the patient-reported Routine Assessment of Patient Index Data 3 (RAPID3) or physician-based Clinical Disease Activity Index (CDAI) for treatment response assessment. Post-hoc analyses identified patients with the SCP, which included diagnosis of depression, fibromyalgia/myalgias, and/or use of medications indicated for treatment of depression, anxiety, or neuropathic pain. The effect of the SCP on RAPID3 or CDAI response at week 12 and low disease activity (LDA; Disease Activity Score in 28 joints based on erythrocyte sedimentation rate ≤ 3.2) at week 52, in week-12 responders, was analyzed using non-parametric analysis of covariance (ANCOVA). RESULTS: At baseline, 43% (313/733) of patients met the SCP classification. Patients with the SCP were 9% more likely to withdraw from the trial. American College of Rheumatology 20% (ACR20), ACR50, and ACR70 responses were 5-14% lower among those with the SCP, and 11% more patients reported adverse events (AEs). Patients without SCP in the CDAI arm were twice as likely to achieve LDA at week 52 compared with those with SCP (32% versus 16%). No differentiation by SCP was observed in the RAPID3 arm (pooled result 21.5%). CONCLUSIONS: We operationalized a potentially important somatization comorbidity phenotype in a trial setting that was associated with a substantially lower likelihood of treatment response and a higher frequency of AEs. Including large numbers of patients with this phenotype in RA trials may reduce the measured clinical effectiveness of a new molecule. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01255761 . Registered on 6 December 2010.
28039964 Degenerative Joint Diseases and Neuroinflammation. 2017 Apr Rheumatic and joint diseases, as exemplified by osteoarthritis and rheumatoid arthritis, are among the most widespread painful and disabling pathologies across the globe. Given the continuing rise in life expectancy, their prevalence is destined to grow. Osteoarthritis, a degenerative joint disease, is, in particular, on its way to becoming the fourth leading cause of disability worldwide by 2020, with the rising incidence of obesity in addition to age being important factors. It is estimated that 25% of osteoarthritic individuals are unable to perform daily activities. Accompanying osteoarthritis is rheumatoid arthritis, which is a chronic systemic disease that often causes pain and deformity. At least 50% of those affected are unable to remain gainfully employed within 10 years of disease onset. A growing body of evidence now points to inflammation, locally and more systemically, as a promoter of damage to joints and bones, as well as joint-related functional deficits. The pathogenesis underlying joint diseases remains unclear; however, it is currently believed that cross-talk between cartilage and subchondral bone-and loss of balance between these two structures in joint diseases-is a critical element. This view is amplified by the presence of mast cells, whose dysregulation is associated with alterations of junction structures (cartilage, bone, synovia, matrix, nerve endings, and blood vessels). In addition, persistent activation of mast cells facilitates the development of spinal neuroinflammation mediated through their interaction with microglia. Unfortunately, current treatment strategies for rheumatic and articular disease are symptomatic and do little to limit disease progression. Research now should be directed at therapeutic modalities that target osteoarticular structural elements and thereby delaying disease progression and joint replacement.
29181398 Rheumatoid Arthritis Affecting the Upper Cervical Spine: Biomechanical Assessment of the S 2017 Diameters of anterior and posterior atlantodental intervals (AADI and PADI) are diagnostically conclusive regarding ongoing neurological disorders in rheumatoid arthritis. MRI and X-ray are mostly used for patients' follow-up. This investigation aimed at analyzing these intervals during motion of cervical spine, when transverse and alar ligaments are damaged. AADI and PADI of 10 native, human cervical spines were measured using lateral fluoroscopy, while the spines were assessed in neutral position first, in maximal inclination second, and in maximal extension at last. First, specimens were evaluated under intact conditions, followed by analysis after transverse and alar ligaments were destroyed. Damage of the transverse ligament leads to an increase of the AADI's diameter about 0.65 mm in flexion and damage of alar ligaments results in significant enhancement of 3.59 mm at mean. In extension, the AADI rises 0.60 mm after the transverse ligament was cut and 0.90 mm when the alar ligaments are damaged. After all ligaments are destroyed, AADI assessed in extension closely resembles AADI at neutral position. Ligamentous damage showed an average significant decrease of the PADI of 1.37 mm in the first step and of 3.57 mm in the second step in flexion, while it is reduced about 1.61 mm and 0.41 mm in the extended and similarly in the neutrally positioned spine. Alar and transverse ligaments are both of obvious importance in order to prevent AAS and movement-related spinal cord compression. Functional imaging is necessary at follow-up in order to identify patients having an advanced risk of neurological disorders.
28993680 Rheumatoid arthritis and risk for Alzheimer's disease: a systematic review and meta-analys 2017 Oct 9 Rheumatoid arthritis (RA) patients have been observed to be at a lower risk of developing Alzheimer's Disease (AD). Clinical trials have showed no relationship between nonsteroidal anti-inflammatory drug (NSAID) use and AD. The aim of this study was to establish if there is a causal link between RA and AD. A systematic literature review on RA incidence and its link to AD was carried out according to the PRISMA guidelines. Eight case-control and two population-based studies were included in a random effects meta-analysis. The causal relationship between RA and AD was assessed using Mendelian Randomization (MR), using summary data from the largest RA and AD Genome Wide Association (GWA) and meta-analysis studies to date using a score of 62 RA risk SNPs (p < 5 * 10(-8)) as instrumental variable (IV). Meta-analysis of the literature showed that RA was associated with lower AD incidence (OR = 0.600, 95% CI 0.46-0.77, p = 1.03 * 10(-4)). On the contrary, MR analysis did not show any evidence of a causal association between RA and AD (OR = 1.012, 95% CI 0.98-1.04). Although there is epidemiological evidence for an association of RA with lower AD incidence, this association does not appear to be causal. Possible explanations for this discrepancy could include influence from confounding factors such as use of RA medication, selection bias and differential RA diagnosis.
29210647 α-Mangostin, A Natural Xanthone, Induces Apoptosis and ROS Accumulation in Human Rheumato 2017 BACKGROUND: Rheumatoid arthritis (RA) is a complicated and heterogeneous chronic disease with the characteristic of progressive joint destruction, deformity and disability. It is associated with not only genetic but also environmental factors. Many studies suggest that RA-derived fibroblast-like synoviocyte (RA-FLS) is involved in the pathogenic process of RA. The apoptosis and proliferation of RA-FLS is of great importance in the development and progression in RA. Nowadays, more and more traditional Chinese medicine (TCM) or natural products are studied in the treatment of RA. OBJECTIVE: To investigate the effects of several natural products and the apoptosisinduced effect of α-mangostin and its underlying mechanisms in RA-FLS MH7A cells. METHODS: The effects of natural products on MH7A cells were detected by MTT assay. Annexin V-FITC/PI double labeling and DAPI staining were adopted to observe the apoptosis induced by α-mangostin. The apoptosis related proteins were measured with western blotting analysis. ROS accumulation was determined by DHE staining. RESULTS: Xantones, including Garcinone C, α-mangostin and γ-mangostin, significantly inhibited the MH7A cell viability. And α-mangostin induces apoptosis in MH7A cells. Further study showed that α-mangostin increased the ratio of Bax/Bcl-2 and increased the ROS generation in MH7A cells. CONCLUSION: α-Mangostin induces the apoptosis of MH7A cells through increasing ROS accumulation and the ratio of Bax/Bcl-2, suggesting that α-mangostin should be benefit to the therapy of RA.
28766390 Burden of rheumatoid arthritis in the Nordic region, 1990-2015: a comparative analysis usi 2018 Mar OBJECTIVE: To report mortality and disability due to rheumatoid arthritis (RA) in the Nordic region (Denmark, Finland, Greenland, Iceland, Norway, and Sweden) using data from the Global Burden of Disease Study (GBD) 2015. METHOD: Using the results of GBD 2015, we present rates and trends in prevalence, mortality, years of life lost, years lived with disability (YLD), and disability-adjusted life-years (DALYs) of RA in the Nordic region during 1990-2015. RESULTS: In 2015, the age-standardized prevalence of RA was higher in the Nordic region than the global level (0.44%, 95% uncertainty interval 0.40-0.48%, vs 0.35%, 0.32-0.38%). For women (men), DALYs increased by 2.4% (12.9%), from 29 263 (10 909) in 1990 to 29 966 (12 311) in 2015. The burden of RA as a proportion of total DALYs in women (men) increased from 0.90% (0.29%) in 1990 to 0.94% (0.36%) in 2015. Age-standardized DALY rates declined in all countries except Denmark and Greenland between 1990 and 2015. Of 315 conditions studied, RA was ranked as the 16th (37th) leading cause of YLD in women (men) in the region. Of 195 countries studied, Greenland, Finland, Denmark, Norway, Sweden, and Iceland had the 7th, 11th, 28th, 38th, 48th, and 78th highest age-standardized YLD rates for RA, respectively. CONCLUSIONS: The prevalence of RA in the Nordic region is higher than the global average. Current trends in population growth and ageing suggest a potential increase in RA burden in the coming decades in the region that should be considered in healthcare resources allocation.
28539558 A case of new-onset rheumatoid vasculitis becoming evident in the course of treatment for 2017   When patients with autoimmune diseases, such as rheumatoid arthritis (RA), are treated with potent immunosuppressive therapy, the risk of opportunistic diseases inevitably increases. If patients have the misfortune to suffer from both opportunistic and active autoimmune diseases, correct diagnosis could sometimes be difficult since both diseases have inflammatory nature. The choice of treatment is another challenge in that aggressive immunosuppressive therapy can fuel the opportunistic infection. Here we report a case of RA patient with new onset rheumatoid vasculitis that was diagnosed in the process of treatment of Pneumocystis jirovecii pneumonia.
27846766 Comparison of a self-administered foot evaluation questionnaire (SAFE-Q) between joint-pre 2017 Sep OBJECTIVES: To clarify the difference of patient-based outcome between joint-preserving arthroplasty and resection-replacement arthroplasty in forefoot surgery for patients with rheumatoid arthritis (RA). METHODS: A total of 63 feet of 49 RA patients who underwent forefoot surgery were asked to answer pre-operative and post-operative self-administered foot evaluation questionnaire (SAFE-Q). Patients were treated with either (1) metatarsal head resection-replacement arthroplasty (28 feet, post-operative mean age 63.8 years, follow-up 4.2 years, DAS28-CRP 2.2) or (2) metatarsophalangeal joint-preserving arthroplasty (35 feet, post-operative mean age 63.1 years, follow-up 3.6 years, DAS28-CRP 2.1) at each surgeon's discretion. RESULTS: Mean pre-operative and post-operative subscale scores of SAFE-Q of group (1) and (2) were as follows. Pain and pain-related [(1) pre-op 36.8 to post-op 75.0 vs. (2) pre-op 42.2 to post-op 82.6], physical functioning and daily-living [(1) 43.2-68.8 vs. (2) 52.778.1], social functioning [(1) 44.3-72.0 vs. (2) 52.5-81.9], general health and well-being [(1) 48.4-68.4 vs. (2) 45.5-84.4], and shoe-related [(1) 30.1-50.3 vs. (2) 30.6-64.4]. Both general health and well-being subscale scores (p < 0.05) and shoe-related subscale scores (p < 0.05) were significantly more improved in group (2) compared with group (1). CONCLUSIONS: Joint-preserving arthroplasty resulted in better patient-based outcomes than resection-replacement arthroplasty.
29181622 Neuromuscular fatigue is weakly associated with perception of fatigue and function in pati 2018 Mar To assess electromyographic parameters of neuromuscular fatigue in knee extensors and their association with clinical, functional and emotional features in patients with rheumatoid arthritis (RA). Thirty-eight female patients with RA participated. Electromyography parameters (changes in signal amplitude, represented by the root mean square, and frequency content, represented by median frequency-MDF) were assessed during a submaximal (60%) isometric contraction of the knee extensors, sustained for 60 s. Clinical characteristics; the 28-joint Disease Activity Score (DAS-28) in which includes count of swollen joints (out of the 28) and tender joints (out of the 28), the erythrocyte sedimentation rate and global disease activity measured on a visual analogue scale; serum C reactive protein (CRP); information on treatment; the Health Assessment Questionnaire; the Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-F); the Short Form Health Survey (SF-36) and the International Physical Activity Questionnaire (IPAQ), were also assessed. The mean patient age was 51.0 ± 8.2 years, mean disease activity score was 11.5 ± 7.1, and mean CRP level was 8.0 ± 7.8 mg/dL. There was a moderate correlation between MDF and age (r = 0.5), as well as weak correlations of MDF with FACIT-F (r = 0.3), physical functioning (r = - 0.3) and vitality domains (r = - 0.3) of the SF-36, and IPAQ (r = - 0.3) (p ≤ 0.05 for all). No association was observed between electromyography measurements and clinical or treatment features. The electromyographic parameter MDF was correlated with perception of fatigue, age, physical functioning and vitality domains of SF-36, and physical activity level in this sample. These results indicate that primary muscle factors should also be considered when managing perceived fatigue in patients with RA.
28905133 RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis 2017 Nov Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3-3.2) as compared to controls (1.3; IQR 0.8-2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15-0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92-4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10-7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00-129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46-4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.
28150104 Assessment of six cardiovascular risk calculators in Mexican mestizo patients with rheumat 2017 Jun Variability of the 10-year cardiovascular (CV) risk predicted by the Framingham Risk Score (FRS) using lipids, FRS using body mass index (BMI), Reynolds Risk Score (RRS), QRISK2, Extended Risk Score-Rheumatoid Arthritis (ERS-RA), and algorithm developed by the American College of Cardiology and the American Heart Association in 2013 (ACC/AHA 2013) according to the European League Against Rheumatism (EULAR) 2015/2016 update of its evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis (RA) has not been evaluated in Mexican mestizo patients. CV risk was predicted using six different risk calculators in 116 patients, aged 40-75, who fulfilled the ACR/EULAR 2010 classification criteria. Results were multiplied by 1.5 according to the EULAR 2015/2016 update. Global comparison of the risk predicted by all scales was done using the Friedman test, considering a P value of ≤0.05 as statistically significant. Individual comparison between the algorithms was made using the Wilcoxon signed-rank test, and a P value of ≤0.003 was considered statistically significant. All calculators showed to be different in the Friedman test (p ≤ 0.001). Median values of predicted 10-year CV risk were 11.02% (6.18-17.55) for FRS BMI; 8.47% (4.6-13.16) for FRS lipids; 5.55% (2.5-11.85) for QRISK2; 5% (3.1-8.65) for ERS-RA; 3.6% (1.5-9.3) for ACC/AHA 2013; and 1.5% (1.5-4.5) for RRS. ERS-RA showed no difference when compared against QRISK2 (p = 0.269). CV risk calculators showed variability among them and cannot be used indistinctly in RA-patients.
28750190 Design and Characterization of a Soft Robotic Therapeutic Glove for Rheumatoid Arthritis. 2019 The modeling and experimentation of a pneumatic actuation system for the development of a soft robotic therapeutic glove is proposed in this article for the prevention of finger deformities in rheumatoid arthritis (RA) patients. The Rehabilitative Arthritis Glove (RA-Glove) is a soft robotic glove fitted with two internal inflatable actuators for lateral compression and massage of the fingers and their joints. Two mechanical models to predict the indentation and bending characteristics of the inflatable actuators based on their geometrical parameters will be presented and validated with experimental results. Experimental validation shows that the model was within a standard deviation of the experimental mean for input pressure range of 0 to 2 bars. Evaluation of the RA-Glove was also performed on six healthy human subjects. The stress distribution along the fingers of the subjects using the RA-Glove was also shown to be even and specific to the finger sizes. This article demonstrates the modeling of soft pneumatic actuators and highlights the potential of the RA-Glove as a therapeutic device for the prevention of arthritic deformities of the fingers.
28103855 Plasma miRNA expression profiles in rheumatoid arthritis associated interstitial lung dise 2017 Jan 19 BACKGROUND: Interstitial lung disease (ILD) is frequently associated with rheumatoid arthritis (RA), and is designated RA-associated ILD (RA-ILD). RA-ILD has a large impact on the prognosis of RA. Here, we investigated the micro RNAs (miRNAs) profiles to determine whether they may be useful for diagnosing RA-ILD. METHODS: RNA was isolated from plasma samples and cDNA was synthesized. Real-time RT-PCR analysis was performed to evaluate 752 miRNA expression profiles in plasma pools from RA patients with or without RA-ILD. Sixteen selected miRNA levels were analyzed in individual plasmas from 64 RA patients with or without RA-ILD. RESULTS: Expression levels of hsa-miR-214-5p (mean relative expression level ± standard deviation, 8.1 ± 28.2 in RA with ILD, 0.2 ± 0.9 in RA without ILD, P = 0.0156) and hsa-miR-7-5p (56.2 ± 260.4 in RA with ILD, 4.7 ± 11.8 in RA without ILD, P = 0.0362) were higher in RA patients with RA-ILD than in those without. The values of miRNA index (214, 7) generated from hsa-miR-214-5p and hsa-miR-7-5p for ILD were significantly elevated in RA patients with RA-ILD compared with those without (0.122 ± 0.332 in RA with ILD, 0.006 ± 0.013 in RA without ILD, P = 0.0010). The area under the curve value of the receiver operating characteristic curve for the miRNA index (214, 7) was 0.740. CONCLUSIONS: To the best of our knowledge, this is the first report of miRNA profiles in RA-ILD. The expression levels of hsa-miR-214-5p and hsa-miR-7-5p were increased in RA with ILD.
27238188 Galectin-3: A key player in arthritis. 2017 Jan Arthritis is more and more considered as the leading reason for the disability in the world, particularly regarding its main entities, rheumatoid arthritis and osteoarthritis. The common feature of arthritis is inflammation, which is mainly supported by synovitis (synovial inflammation), although the immune system plays a primary role in rheumatoid arthritis and a secondary one in osteoarthritis. During the inflammatory phase of arthritis, many pro-inflammatory cytokines and mediators are secreted by infiltrating immune and resident joint cells, which are responsible for cartilage degradation and excessive bone remodeling. Amongst them, a β-galactoside-binding lectin, galectin-3, has been reported to be highly expressed and secreted by inflamed synovium of rheumatoid arthritis and osteoarthritis patients. Furthermore, galectin-3 has been demonstrated to induce joint swelling and osteoarthritis-like lesions after intra-articular injection in laboratory animals. However, the mechanisms underlying its pathophysiological role in arthritis have not been fully elucidated. This review deals with the characterization of arthritis features and galectin-3 and summarizes our current knowledge of the contribution of galectin-3 to joint tissue lesions in arthritis.
28578645 The Anti-Migraine Effects of M2000 (β-D-Mannuronic Acid) on a Patient with Rheumatoid Art 2017 BACKGROUND: Rheumatoid arthritis (RA) and migraine are both common disorders which are caused by a faulty immune system and autonomic nervous system dysfunction, respectively. Although current treatment outlook has shown a great improvement in these two diseases, however many side effects have been reported. CASE REPORT: We reported a case of 43-years-female that has suffered from rheumatoid arthritis for 3 years with a 6 years history of migraine. She had used different types of medication for both rheumatoid arthritis and migraine but during these 6 years no improvement had been observed and even migraine progression in this patient became worse. She was admitted to the hospital for 12 weeks follow-up to evaluate the effect of β-D-mannuronic acid (M2000) on her RA disease. MATERIALS AND METHODS: During 12 weeks of M2000 therapy, the signs and symptoms of migraine along with RA indices including Disease Activity Score (DAS28), simple disease activity index (SDAI) and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP) and blood determinants were measured. RESULTS AND DISCUSSION: The patient achieved a strong clinical improvement after 12 weeks of M2000 therapy in DAS28, SDAI and laboratory parameters. Moreover, M2000 showed a significant effect on the severity and the duration of migraine pain as well as times of migraine attack. In the present case, both rheumatoid arthritis and migraine as two different inflammatory diseases were diagnosed. Therefore, reducing the inflammation could be a valuable target to decrease the signs and symptoms of migraine and rheumatoid arthritis and help to the treatment process. CONCLUSION: M2000 as a novel designed non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive property is able to treat migraine in addition to its potent efficacy on treatment of rheumatoid arthritis.
27510601 Association between antiphospholipid antibodies and arterial thrombosis in patients with r 2017 Jan OBJECTIVES: Antiphospholipid antibodies (aPL) are present in a proportion of patients with rheumatoid arthritis but their clinical significance remains unclear. We investigated the association between aPL and thrombotic events in rheumatoid arthritis patients. METHODS: In this cross-sectional study, aPL profiles were evaluated in 376 rheumatoid arthritis patients in accordance with the standard guidelines. Clinical and radiographic data were retrospectively collected. RESULTS: aPL were identified in 39 patients (10.4%). Lupus anticoagulant was the most common subtype (n = 25, 6.6%); anti-cardiolipin antibodies and anti-β(2) glycoprotein I antibodies were detected in six and 12 patients (1.6% and 3.2%), respectively. Compared to the aPL-negative group, aPL-positive patients included more male patients (41.0% vs. 15.4%, P < 0.001) and more smokers (41.0% vs. 16.0%, P = 0.001). There was no difference between the two groups in age, disease duration and body mass index, or the frequency of diabetes, hypertension or dyslipidaemia. Of note, arterial thromboses were more common in the aPL-positive than the aPL-negative group (12.8% vs. 2.1%, P = 0.004), whereas the frequency of venous thrombosis did not differ between the two groups (0.0% vs. 0.9%, P = 1.000). On multivariate regression analysis, aPL, age, hypertension, dyslipidaemia and baseline C-reactive protein level were independently associated with arterial thrombotic events (all P values < 0.05). CONCLUSION: aPL was found in a subset of rheumatoid arthritis patients, who were more often smokers, and aPL was independently associated with development of arterial thrombosis. This result suggests that aPL may contribute to an increased risk of arterial thrombosis in rheumatoid arthritis patients.
27601627 Low-density granulocytes: functionally distinct, immature neutrophils in rheumatoid arthri 2017 Feb Our aim was to determine whether rheumatoid arthritis (RA) low-density granulocytes (LDGs) are functionally different from RA neutrophils. LDGs from 32 RA patients were characterized using flow cytometry and quantitative PCR (qPCR). RNA sequencing (RNA-Seq) was carried out on paired RA LDGs and neutrophils (n = 4) and validated using qPCR. Functional assays included chemotaxis, phagocytosis, reactive oxygen species (ROS) production, cell-cycle analysis, apoptosis, neutrophil extracellular trap (NET)osis, and measurement of cytokine production (n ≥ 5 paired RA LDGs/neutrophils). RA LDGs had a substantially altered transcriptome, expressing >5000 genes at significantly different levels compared with RA neutrophils, including elevated levels of transcripts for granule proteins [including elastase and myeloperoxidase (MPO)] and cell-cycle genes [including cyclin-dependent kinase (CDK)2, CDK4, and CDK6]. Approximately 1% of RA LDGs stained positive for the G2/S phase of the cell cycle. RA LDGs had a significantly lower constitutive rate of apoptosis compared with RA neutrophils and did not respond to TNF-α in culture. Expression of transcripts for cytokines and cytokine receptors was lower in RA LDGs. NET formation was lower in LDGs in response to PMA compared with RA neutrophils. Chemotaxis and phagocytosis was lower in RA LDGs compared with neutrophils. RA LDGs produced significantly lower amounts of ROS in response to fMLP following priming with TNF-α. Expression of TNFR1 and -2 mRNA and protein was significantly lower in LDGs. We conclude that RA LDGS are functionally different from RA neutrophils, representing an immature neutrophil population within peripheral blood. Their enhanced survival properties and decreased TNF signaling are likely to have important consequences for disease pathology and response to therapy.
27686747 Neutrophil-to-lymphocyte ratio is a reliable marker of treatment response in rheumatoid ar 2017 May OBJECTIVE: To investigate the reliable markers reflecting treatment response better than the traditional inflammatory indices in patients with rheumatoid arthritis (RA) receiving tocilizumab therapy. METHODS: A total of 58 RA patients treated with tocilizumab for more than six months from January 2013 to December 2014 were initially included. Flares were defined as events that required steroid dose escalation, intra-articular steroid injections, or switching tocilizumab to other biologic agents. The clinical and laboratory data were retrospectively collected from electronic medical records. RESULTS: Of the 52 patients except for six patients who were excluded, 16 experienced flares, and 36 were stable during tocilizumab therapy. The C-reactive protein (CRP) level did not significantly differ between a stable state before flares and at flares. Compared with those at the preflare time point, erythrocyte sedimentation rate (ESR), and neutrophil to lymphocyte ratio (NLR) were significantly higher at flares; however, ESR levels (n = 9) were within the normal limit or decreased (n = 4) at flares. Interestingly, NLR increased at flares in all but one patient in the flare group. CONCLUSION: NLR is a more reliable marker than ESR or CRP for evaluating the disease activity in patients with RA during tocilizumab therapy.
28127980 Speckle tracking can detect subclinical myocardial dysfunction in rheumatoid arthritis pat 2017 INTRODUCTION: Patients with rheumatoid arthritis (RA) have shorter life expectancy and their risk of cardiovascular death is more than 50 % higher than the rest of the population. Early myocardial dysfunction in RA patients may be detectable sooner using speckle‑tracking echocardiography. METHOD: Cross-sectional study enrolled 55 patients with RA (mean age 44.1 years) without known cardiovascular disease and 31 healthy controls. All subjects underwent a standard echocardiographic examination: indexed left ventricular mass, left ventricle ejection fraction, isovolumic contraction and relaxation times (IVCT and IVRT), mitral valve inflow curve (E/A), septal mitral annular motion (e'), and E/e' ratio as well as the speckle tracking assessment of left ventricle longitudinal, radial and circular strain and strain rate. RESULTS: In standard echocardiographic examination RA patients exhibited higher indexed left ventricle mass (96.36±20.90 g/m2 vs 95.84±21.86 %, p=0.013), lower ejection fraction (64.84±3.87 % vs 67.10±3.87 %, p=0.011) and prolonged IVCT (61.51±9.30 ms vs 53.71±8.95 ms, p=0.001). Diastolic dysfunction was demonstrated by prolonged IVRT (81.62±9.56 ms vs 74.58±12.02 ms, p=0.007) as well as by higher E/e' ratio (8.21±1.76 vs 7.21±1.52, p=0.009). Speckle‑tracking method detected lower global longitudinal epicardial strain (-19.51 % vs -21.46 %, p=0.049). Radial, circular, and transversal strains and strain rates were same in both groups. Global longitudinal epicardial strain correlated with IVCT and IVRT, disease duration, and markers of myocardial damage NTproBNP. CONCLUSIONS: Standard echocardiographic assessment of myocardial function is examiner- and angle-dependent method with considerable limitations for evaluation of minimal subclinical changes. Speckle-tracking echocardiography significantly revealed incipient myocardial dysfunction in RA patients without overt cardiovascular diseases. This correlates with clinical RA characteristics and markers of cardiac damage (Tab. 4, Ref. 48).
27572743 Hydrogen Sulfide and Inflammatory Joint Diseases. 2017 BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) are widespread rheumatic diseases characterized by persistent inflammation and joint destruction. Hydrogen sulfide (H2S) is an endogenous gas with important physiologic functions in the brain, vasculature and other organs. Recent studies have found H2S to be a mediator in inflammatory joint diseases. OBJECTIVE: This review summarizes the recent literature in this area highlighting relevant developments. CONCLUSIONS: Several authors have found that H2S exhibited anti-inflammatory, anti-catabolic and/or anti-oxidant effects in rodent models of acute arthritis and in in vitro models using human synoviocytes and articular chondrocytes from RA and OA tissues. The earliest studies used fast-dissolving salts, such as NaSH, but GYY4137, which produces H2S more physiologically, shortly appeared. More recently still, new H2S-forming compounds that target mitochondria have been synthesized. These compounds open exciting opportunities for investigating the role of H2S in cell bioenergetics, typically altered in arthritides. Positive results have also been obtained when H2S is administered as a sulphurous water bath, an option meriting further study. These findings suggest that exogenous supplementation of H2S may provide a viable therapeutic option for these diseases, particularly in OA.