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ID PMID Title PublicationDate abstract
28373873 Novel Senescent Regulatory T-Cell Subset with Impaired Suppressive Function in Rheumatoid 2017 OBJECTIVE: Premature senescence of lymphocytes is a hallmark of inflammatory rheumatic diseases such as rheumatoid arthritis (RA). Early T-cell aging affects conventional T-cells but is presumably not limited to this cell population; rather it might also occur in the regulatory T-cells (Tregs) compartment. In RA, Tregs fail to halt aberrant immune reactions and disease progression. Whether this is associated with early Treg senescence leading to phenotypic and functional changes of this subset is elusive so far. METHODS: Eighty-four RA patients and 75 healthy controls were prospectively enrolled into the study. Flow cytometry, magnetic-associated cell sorting, and cell culture experiments were performed for phenotypic and functional analyses of Treg subsets. T-cell receptor excision circle (TREC) levels and telomere lengths were determined using RT-PCR. RESULTS: In this paper, we describe the novel CD4(+)FoxP3(+)CD28(-) T-cell subset (CD28(-) Treg-like cells) in RA patients revealing features of both Tregs and senescent T-cells: Treg surface/intracellular markers such as CD25, CTLA-4, and PD-1 as well as FOXP3 were all expressed by CD28(-) Treg-like cells, and they yielded signs of premature senescence including reduced TREC levels and an accumulation of γH2AX. CD28(-) Treg-like could be generated in vitro by stimulation of (CD28(+)) Tregs with TNF-α. CD28(-) Treg-like cells insufficiently suppressed the proliferation of effector T-cells and yielded a pro-inflammatory cytokine profile. CONCLUSION: In conclusion, we describe a novel T-cell subset with features of Tregs and senescent non-Tregs. These cells may be linked to an aberrant balance between regulatory and effector functions in RA.
28361468 Impact of Participation in the Adalimumab (Humira) Patient Support Program on Rheumatoid A 2017 Jun INTRODUCTION: Patients with rheumatoid arthritis (RA) who are treated with adalimumab (ADA) are offered a proprietary patient support program (PSP, AbbVie Care(®)). The main objective of this study was to examine the effectiveness of ADA on RA treatment course over time in the context of PSP utilization. METHODS: PASSION was a 78-week post-marketing observational study of RA patients with an insufficient response to ≥1 DMARD newly initiating ADA in routine clinical care that was conducted in Europe, Israel, Mexico, Puerto Rico, and Australia. One prior biologic DMARD was allowed. The primary endpoint was percentage of patients achieving the minimal clinically important difference (MCID; improvement of ≥0.22 compared to baseline) in Health Assessment Questionnaire (HAQ) Disability Index (HAQ-DI) at week 78. Additionally, multiple clinical and patient-reported outcomes (PROs) were evaluated over time. Patients were categorized based on their participation in the PSP: ever (PSP users) vs. never (PSP non-users). Safety events were monitored throughout the study. RESULTS: Overall, 42.8% of PSP users achieved the MCID in HAQ-DI at week 78 (improvement of at least 0.22 compared to baseline). From 1025 enrolled, 48.7% of patients were PSP users while treated with ADA. The percentage of patients achieving MCID in the HAQ-DI was higher in PSP users vs. PSP non-users (48.1 vs. 37.8%) at week 78 (p < 0.001, NRI). Most of the studied clinical outcomes and PROs showed significant improvements (p < 0.05) from baseline to week 78 favoring PSP users over PSP non-users. CONCLUSIONS: In patients with moderate-to-severe RA who initiated ADA, improvements in clinical, functional, and PROs were achieved in real-world settings with significantly greater improvements among PSP users in comparison with PSP non-users. FUNDING: AbbVie. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01383421.
27846746 Minimum 10-year results of cementless total hip arthroplasty in patients with rheumatoid a 2017 Jul OBJECTIVES: To retrospectively evaluate the long-term results of cementless total hip arthroplasty (THA) in patients with rheumatoid arthritis (RA) and postoperative patient mortality after THA. METHODS: This study included 191 hips in 149 RA patients who underwent cementless THA between 1998 and 2005. Mean age at surgery was 54.2 years, and mean follow-up was 12.6 years. Implant and patient survivorships were determined using the Kaplan-Meier method, and the associated influencing factors were determined. RESULTS: Implant survivals at 17 years were 99.5% for stems, 93.9% for cups, and 90.8% for liners. Among the liners used, THAs with highly cross-linked polyethylene showed better survivals compared with those with conventional polyethylene and alumina-bearing surface (93.4%, 90.9%, and 52.2%, respectively). A total of 64 deaths occurred; 45 patients died within 10 years and 19 patients died between 10 and 17 years. Malignancy (25.0%) was the leading cause of death, followed by pneumonia (20.8%) and sepsis (20.8%). The patient survival rate was 36.9% at 17 years after THA. Multivariate analysis exhibited that older age at operation and greater dose of concomitant corticosteroid resulted in shorter patient survivals. CONCLUSIONS: Cementless THA worked well in patients with RA. Mortality remained high among RA patients who needed THA.
28270933 No impact of concomitant methotrexate use on serious adverse event and serious infection r 2017 OBJECTIVES: To compare the risk of serious adverse events, serious infections and death caused by methotrexate and biological disease-modifying antirheumatic drug (bDMARD) combination therapy versus a bDMARD prescribed as monotherapy in rheumatoid arthritis (RA). METHODS: A systematic literature review was conducted until February 2016 in PubMed, Embase and Cochrane Library databases by selecting randomised controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy in RA. The meta-analysis compared the occurrence of (1) serious adverse events, (2) serious infections and (3) death among these groups by the Mantel-Haenszel method. RESULTS: The literature review selected 16 controlled trials comparing methotrexate and bDMARD combination therapy to bDMARD monotherapy. After meta-analysis comparing patients under monotherapy to those under combination therapy: (1) the risk of occurrence of serious adverse events was comparable in 12 trials: RR (95% CI) 0.92 (0.78 to 1.08). (2) No significant difference was observed in the risk of occurrence of serious infections in 13 trials: RR (95% CI) 1.15 (0.84 to 1.58). We noted a trend, although insignificant, towards a high risk of the occurrence of tuberculosis in 10 studies: RR (95% CI) 1.78 (0.63 to 4.99). (3) The risk of death was comparable in 12 trials: RR (95% CI) 0.73 (0.40 to 1.35). CONCLUSIONS: The results showed no significant difference between the two groups, confirming that the use of methotrexate and bDMARD combination therapy in RA does not cause an increased risk of serious adverse events or serious infections or death compared with bDMARD monotherapy.
29901021 Crosslinks Between Human Leukocyte Antigen DRB1*01 and Human Leukocyte Antigen DRB1*13 All 2017 Dec OBJECTIVES: This study aims to analyze human leukocyte antigen A (HLA-A), human leukocyte antigen B (HLA-B), human leukocyte antigen C (HLA-C), HLA-DRB1*, HLA-DRB3*, HLA-DRB4*, HLA-DRB5*, HLA-DQB1* loci expression in patients with rheumatoid arthritis (RA) in the Federation of Bosnia and Herzegovina. PATIENTS AND METHODS: Deoxyribonucleic acid was isolated from peripheral blood of 48 RA patients (22 males, 26 females; mean age 36 years; range 2 to 63 years) and 104 healthy control individuals (52 males, 52 females; mean age 43 years; range 2 to 76 years). Deoxyribonucleic acid samples were analyzed using polymerase chain reaction-sequence-specific primers and sequence specific oligonucleotides methods. RESULTS: The most frequent allelic groups in RA patients were HLA-DRB1*01 (odds ratio=2.795; 95% confidence interval: 1.441-5.421; p=0.004) and HLA-DRB1*04 (odds ratio=2.573; 95% confidence interval: 1.214-5.453; p=0.023). Among RA patients, the most frequent genotype for the allelic group HLA-DRB1*, in the light of the common epitopes theory, was observed for DRB1*01/DRB1*13. This genotype indicates an increased incidence and relative risk (odds ratio=11.09). CONCLUSION: The most common genotype in our RA patients was DRB1*01/DRB1*13, which showed increased frequency and a high relative risk. This genotype variant may be considered a predisposing factor for the development of RA.
29417020 Prevalence of left ventricular dysfunction in rheumatoid arthritis. 2017 Jul BACKGROUND: Rheumatoid arthritis (RA) is a polyarticular disorder with many extra-articular features. Cardiovascular disorders, including heart failure (HF), are the leading causes of mortality in RA patients. We studied the prevalence of left ventricular dysfunction (LVD) in patients with RA. MATERIALS AND METHODS: In this cross-sectional study, we evaluated 100 consecutive patients with RA (aged >18 years and duration >1 year) for the presence of LVD. We excluded patients with known cardiac and systemic disorders that may contribute to LVD. LVD is defined by the presence of either left ventricular systolic dysfunction (LVSD) or left ventricular diastolic dysfunction (LVDD), evaluated by the echocardiography. Descriptive statistics and relevant tests were used to analyze the results. RESULTS: The study participants (n = 100; 80F and 20M) had a mean age of 45 ± 11.8 years, duration of disease 7.4 ± 5.4 years, and disease activity score of 3.5 ± 1.1. A total of 46 patients had symptoms of HF, but only 14% of them had signs of HF. LVD was seen in 59 (LVSD-4, LVDD-50, and both together in 5) patients, and none of the participants had severe grades of LVSD and LVDD. LVD showed no relation to the age of the patients (P = 0.186) and it was more with increasing duration of RA (P < 0.001) and higher disease activity (P = 0.042). CONCLUSION: LVD is more common in RA patients, which increases the associated morbidity and mortality. Higher threshold is required by the family practitioners to perform a screening echocardiography in long-standing RA patients.
29226077 Leptin-induced migration and angiogenesis in rheumatoid arthritis is mediated by reactive 2017 Dec Rheumatoid arthritis (RA) is a progressive autoimmune disease affecting the joints. In this study, we investigated the role of the pro-angiogenic factor leptin in regulating reactive oxygen species (ROS) to promote cell migration and angiogenesis in RA. We showed that leptin triggered RA fibroblast-like synoviocyte (FLS) migration by increased ROS expression. Additionally, leptin enhanced human umbilical vein endothelial cell (HUVEC) tube formation in a ROS/hypoxia-inducible factor-1α-dependent manner, accompanied by increased production of vascular endothelial growth factor and interleukin (IL)-6. We also revealed that antagonists of tumor necrosis factor, IL-6 and IL-1β down-regulated ROS production of RA FLS induced by leptin, which subsequently attenuated RA FLS migration and HUVEC tube formation. These findings demonstrated that leptin might play an important role in RA FLS migration and HUVEC angiogenesis.
29204091 Lipocalin 2 as a clinical significance in rheumatoid arthritis. 2017 AIM OF THE STUDY: In this study, serum lipokalin 2 (LCN-2) levels and its clinical and radiological significance in patients with rheumatoid arthritis was evaluated. MATERIAL AND METHODS: The study enrolled 37 patients with RA and 34 healthy controls. Serum LCN-2 level was measured using ELISA method. Patients with DAS 28 scores ≤ 3.2, and > 3.2 were allocated into lower and high/moderate disease activity groups, respectively. Additionally patients were divided into 2 groups as early RA (disease duration ≤ 2 years) and established RA (duration of the disease ≥ 2 years). Functional disability was evaluated using Health Assessment Questionnaire (HAQ). Radiographs were scored using the modified Larsen score. RESULTS: Serum LCN-2 (p = 0.029) levels were significantly higher in patients with RA than in the controls. Serum LCN-2 level did not correlate with laboratory and clinical parameters of disease activity like erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), DAS 28, Health Assessment Questionnaire Score (HAQ) and Nottingham Health Profile (NHP). Similarly, any correlation could not be found between structural joint damage and serum LCN2 levels. CONCLUSIONS: These results indicate that serum LCN-2 levels may be used as an indicator for structural damage like erosions in the early stage of the disease but do not able to be used to monitor disease activity.
29184453 Physical activity and sedentary behavior in patients with systemic lupus erythematosus and 2017 OBJECTIVE: Patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). As sedentary behavior and lack of physical activity are known cardiovascular risk factors, we compared habitual activity between SLE patients, RA patients, and healthy control participants. PATIENTS AND METHODS: For this cross-sectional study, RA and SLE patients were recruited from rheumatology clinics at an academic medical center from April 2013 to December 2014. Healthy control participants were recruited through local advertising during the same time period. Habitual activity was measured using a triaxial accelerometer worn during waking hours for 7 consecutive days. Minutes per day of sedentary, light, and moderate-vigorous physical activity (MVPA) were recorded and compared between SLE, RA, and healthy participants using ANOVA. RESULTS: There were 59 participants included in the analysis: 20 SLE patients, 19 RA patients, and 20 healthy controls. Disease activity was quiescent in both the SLE and RA groups. All three groups demonstrated high sedentary behavior (mean ± SD sedentary time for all participants: 10.1±1.3 hours/day; 76.4% total wear time). There were no significant differences between SLE, RA, and healthy participants in time spent in sedentary behavior (p=0.80) or light activity (p=0.17). Total MVPA (mean ± SD, minutes/day) was significantly lower in SLE (34.5±22.7; p<0.001) and RA (41.5±21.3; p=0.005) patients compared to controls (64.9±22.4). CONCLUSION: SLE and RA patients demonstrate suboptimal MVPA despite well-controlled disease. Given their increased CVD risk, effective interventions are required to improve habitual physical activity levels in both populations.
28761564 Predictive Value of Serum Infliximab Levels at Induction Phase in Rheumatoid Arthritis Pat 2017 BACKGROUND: The Infliximab, has proven effective in treating rheumatoid arthritis (RA). A good clinical response is usually associated with high serum drug levels. Development of antibodies toward Infliximab (ATI) can increase drug clearance, leading to treatment failure. AIMS: To analyze whether serum Infliximab trough levels (ITL) at the induction phase are associated with Infliximab clearance and clinical outcomes at week(W) 54 and to investigate the association with immunogenicity development. METHODS: Observational retrospective study in which ITL from 66 RA patients were measured by capture ELISA at W0, W2, W6, W14 and 22. Patients were classified as ITLpos if Infliximab was detectable at W54 and ITLneg otherwise. ATI were assayed by bridging ELISA and by two drug-tolerant assays. ITL cut-off values were established by ROC curves. The association between ITL at early-stage and clearance of Infliximab at W54 was analyzed by univariable and multivariable logistic regression. RESULTS: ITLneg patients (n=25) always had significantly lower Infliximab levels than ITLpos (n=41). An ITL value of 4.4 μg/mL at W6 best predicted W54 Infliximab absence. In the multivariable analysis, only ITL below the cut-off at W6 (OR: 86.6; 95%CI: 6.58-1139.99) and non-use of methotrexate (OR: 6.9; 95%CI: 1.04-45.84) remained significantly associated with W54 Infliximab absence. ATI were more frequent in patients with ITL below the cut-off at W6. CONCLUSIONS: In RA, ITL at induction phase are inversely associated with Infliximab clearance and clinical outcomes at W54. ATI was the main reason for low early ITL. A predictive value of ITL at W6 was found as a useful prognostic measure of treatment efficacy.
27241704 Biosimilars in rheumatology: understanding the rigor of their development. 2017 Feb This article examines the current landscape of biosimilar development in rheumatology. As misperceptions about biosimilars exist regarding their comparability to the reference products for clinical use, we review the development paradigm with the goal of improving rheumatologists' understanding of the rigor with which biosimilars are developed. With an emphasis on European Union and US markets, it gives an overview of some of the challenges and issues related to biosimilar development that need to be considered by rheumatologists in this increasingly growing therapeutic space.
28862467 Clinical, Imaging, and Laboratory Findings in Sjögren's Syndrome. 2017 Sep Sjögren's syndrome (SS) is a rare condition characterized by structural damage and secretory dysfunction of the lacrimal and salivary glands that leads to dryness, particularly xerophthalmia (eyes) and xerostomia (mouth). No cure is known; however, the effects of the disease are manageable and symptoms may be reduced. Although the salivary damage is irreversible, the dental decay and oral infections may be prevented, which highlights the importance that the clinician plays in the diagnosis and management of SS. The cardinal features of this disease are summarized through the case report of primary SS in a 23-year-old woman who received an early diagnosis based on clinical features, laboratory investigations, lower lip biopsy, and imaging findings.
32185263 Determining the presence of Peripheral Arterial Disease in patients with Rheumatoid Arthri 2017 Jun OBJECTIVES: The aim of the study was to determine the manifestations of PAD in a population of RA participants with no history of cardiovascular events. METHODS: A prospective observational non-experimental study was conducted on 100 participants presenting with RA and no history of significant cardiovascular events. Vascular assessment including Doppler spectral waveform analysis and Ankle Brachial Pressure Index was conducted. RESULTS: Triphasic waveforms was found in the Posterior Tibial Artery (PT) in 70% right foot, 66% left foot and Dorsalis Pedis Artery (DP) in both feet in the64% of the patients. Twenty-nine per cent of the participants had biphasic PT right foot and 33% had biphasic PT left foot. Thirty-six per cent had biphasic DP both feet whilst only one participant (1%) had a discontinuous monophasic PT of both feet. The ABPI readings were found to be normal in 96% of participants and mild PAD was found in only 4% of the study population. CONCLUSIONS: Results indicate that whilst the ABPI index was normal in the majority of participants, waveform analysis was suboptimal (biphasic) in approximately one-third of the study sample. These findings highlight that the assessment of peripheral arterial perfusion should utilize both modalities to identify patients with early PAD.
31548521 Epitope Specificity of Anti-Citrullinated Protein Antibodies. 2017 Mar 8 Anti-citrullinated protein antibodies are primarily associated with a progressive course in the autoimmune disease rheumatoid arthritis, a disease with a chronic and inflammatory nature. These antibodies do not appear to have any strict dependency for reactivity except from the presence of the non-genetically encoded amino acid citrulline, which is the result of a posttranslational modification, catalyzed by calcium-dependent peptidylarginine deiminase enzymes. Nevertheless, several amino acids surrounding the citrulline residue notably influence antibody reactivity, especially with a central-Cit-Gly-motif being essential for antibody reactivity. Most importantly, these antibodies have been proposed to be divided into two groups, based on their ability to recognize multiple citrullinated peptides. Thus, an "overlapping" antibody group, which appears to recognize several citrullinated peptides, and a "non-overlapping" antibody group, which only recognizes a limited number of citrullinated peptides, have been proposed. Based on these findings, we suggest that antibodies recognizing several citrullinated targets, also referred to as cross-reactive antibodies, primarily are backbone-dependent, whereas less cross-reactive antibodies primarily depend on the side chains of the amino acids comprising the epitopes for stable antibody-antigen interactions, which reduces the degree of cross-reactivity significantly. Clarifying the reactivity pattern of anti-citrullinated protein antibodies may contribute to determining their true nature of origin.
29123529 T Cell-Mediated Chronic Inflammatory Diseases Are Candidates for Therapeutic Tolerance Ind 2017 Failing immunological tolerance for critical self-antigens is the problem underlying most chronic inflammatory diseases of humans. Despite the success of novel immunosuppressive biological drugs, the so-called biologics, in the treatment of diseases such rheumatoid arthritis (RA) and type 1 diabetes, none of these approaches does lead to a permanent state of medicine free disease remission. Therefore, there is a need for therapies that restore physiological mechanisms of self-tolerance. Heat shock proteins (HSPs) have shown disease suppressive activities in many models of experimental autoimmune diseases through the induction of regulatory T cells (Tregs). Also in first clinical trials with HSP-based peptides in RA and diabetes, the induction of Tregs was noted. Due to their exceptionally high degree of evolutionary conservation, HSP protein sequences (peptides) are shared between the microbiota-associated bacterial species and the self-HSP in the tissues. Therefore, Treg mechanisms, such as those induced and maintained by gut mucosal tolerance for the microbiota, can play a role by targeting the more conserved HSP peptide sequences in the inflamed tissues. In addition, the stress upregulated presence of HSP in these tissues may well assist the targeting of the HSP induced Treg specifically to the sites of inflammation.
28829212 Targeting methionine cycle as a potential therapeutic strategy for immune disorders. 2017 Aug 23 Methionine cycle plays an essential role in regulating many cellular events, especially transmethylation reactions, incorporating the methyl donor S-adenosylmethionine (SAM). The transmethylations and substances involved in the cycle have shown complicated effects and mechanisms on immunocytes developments and activations, and exert crucial impacts on the pathological processes in immune disorders. Areas covered: Methionine cycle has been considered as an effective means of drug developments. This review discussed the role of methionine cycle in immune responses and summarized the potential therapeutic strategies based on the cycle, including SAM analogs, methyltransferase inhibitors, S-adenosylhomocysteine hydrolase (SAHH) inhibitors, adenosine receptors specific agonists or antagonists and homocysteine (Hcy)-lowering reagents, in treating human immunodeficiency virus (HIV) infections, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis (SSc) and other immune disorders. Expert opinion: New targets and biomarkers grown out of methionine cycle have developed rapidly in the past decades. However, impacts of epigenetic regulations on immune disorders are unclear and whether the substances in methionine cycle can be clarified as biomarkers remains controversial. Therefore, further elucidation on the role of epigenetic regulations and substances in methionine cycle may contribute to exploring the cycle-derived biomarkers and drugs in immune disorders.
29719460 Korean Red Ginseng exhibits no significant adverse effect on disease activity in patients 2018 Apr BACKGROUND: Panax ginseng is a well-known immune modulator, and there is concern that its immune-enhancing effects may negatively affect patients with rheumatoid arthritis (RA) by worsening symptoms or increasing the risk of adverse effects from other drugs. In this randomized, crossover clinical trial, we evaluated the impact of Korean Red Ginseng (KRG) on disease activity and safety in RA patients. METHODS: A total of 80 female RA patients were randomly assigned to either the KRG (2 g/d, n = 40) treatment or placebo (n = 40) groups for 8 wk, followed by crossover to the other treatment group for an additional 8 wk. The primary outcome was the disease flare rate, defined as worsening disease activity according to the disease activity score 28 joints-erythrocyte sedimentation rate (DAS28-ESR). The secondary outcomes were development of adverse events (AEs) and patient reported outcomes. Outcomes were evaluated at baseline and 8 wk and 16 wk. The outcomes were compared using the Chi-square test. RESULTS: Of the 80 patients, 70 completed the full study. Their mean age was 51.9 yr, and most exhibited low disease activity (mean DAS28-ESR 3.5 ± 1.0) at enrollment. After intervention, the flare rate was 3.7% in each group. During KRG treatment, 10 AEs were reported, while five AEs were developed with placebo; however, this difference was not statistically significant (p = 0.16). Gastrointestinal- and nervous system-related symptoms were frequent in the KRG group. CONCLUSION: KRG is not significantly associated with either disease flare rate or the rate of AE development in RA patients.
29225920 Relationship between shift work and the onset of rheumatoid arthritis. 2017 BACKGROUND: Environmental factors play a prominent role in rheumatoid arthritis (RA) aetiology. Shift work has previously been associated with increased RA risk in females. The aim of this study was to investigate the potential association, including a dose-response association, between permanent night shift work, rotating shift work and day-oriented shift work and risk of developing anticitrullinated peptide antibodies (ACPA)-positive and ACPA-negative RA. METHODS: The present report is based on a population-based, case-control study with incident cases of RA (1951 cases and 2225 controls matched by age, gender and residential area). Using logistic regression, occurrence of RA among subjects who have been exposed to different kinds of shift work was compared with that among those who have never been exposed by calculating the OR with a 95% CI. RESULTS: Rotating shift work and day-oriented shift work increased the risk of developing ACPA-positive RA (OR 1.3, 95% CI 1.0 to 1.7 and OR 1.3, 95% CI 1.0 to 1.6), but not ACPA-negative RA. Permanent night shift work appeared to be a protective factor both against ACPA-positive RA (OR 0.7, 95% CI 0.6 to 0.9) and ACPA-negative RA (OR 0.8, 95% CI 0.6 to 1.0). For both subsets of RA, significant trends showed a lower risk of developing RA with increasing duration of permanent night shift work (p value for trend 0.002 vs 0.04). CONCLUSIONS: Sleep restriction as a consequence of shift work is associated with several biological effects among which changes in melatonin production may be involved. The present epidemiological findings of a complex relationship between sleep patterns and different forms of RA may be of importance for increasing the understanding of the pathophysiology of RA.
31966382 Circulating lnc-ITSN1-2 expression presents a high value in diagnosis of rheumatoid arthri 2017 This study was aimed to investigate the correlation of lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1 expressions in plasma by qPCR with rheumatoid arthritis (RA) risk and disease activity. 30 RA patients and 30 health controls (HC) were enrolled in this study. Plasma sample were collected from RA patients before any treatment carried out and HCs. Top 3 RA related long non-coding RNAs (lncRNAs) (lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1) were selected by a computational framework prediction. The expression of lnc-ITSN1-2, lnc-APOC3-2 and lnc-AL355149.1 were determined by qPCR method. Age (P=0.350) and gender (P=0.542) were similar between RA patients and HCs. lnc-ITSN1-2 level was extremely increased in RA patients compared with HCs (P<0.001), while both lnc-APOC3-2 and lnc-AL355149.1 expressions were numerically higher in RA patients but with no statistical significance (P=0.152 and P=0.139 respectively). Receiver Operating Characteristic (ROC) curves were performed and we found lnc-ITSN1-2 disclosed a great diagnostic value for RA with area under curve (AUC) 0.898, 95% CI 0.813-0.983, and sensitivity was 90.0% and specificity was 80.0% respectively at the best cut-off point. In addition, plasma lnc-ITSN1-2 level was illuminated to be positively associated with erythrocyte sedimentation rate (ESR) (P=0.049), C-reactive protein (CRP) (P<0.001) and disease activity score in 28 joints (DAS28) (P=0.007). Circulating lnc-ITSN1-2 expression was observed to be a novel and convincing biomarker for RA diagnosis as well as disease management.
28955481 Methotrexate and low-dose prednisolone downregulate osteoclast function by decreasing rece 2017 OBJECTIVE: Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease that ultimately leads to bone erosions and joint destruction. Methotrexate (MTX) slows bone damage but the mechanism by which it acts is still unknown. In this study, we aimed to assess the effect of MTX and low-dose prednisolone (PDN) on circulating osteoclast (OC) precursors and OC differentiation in patients with RA. METHODS: Patients with RA before and at least 6 months after MTX therapy were analysed and compared with healthy donors. A blood sample was collected in order to assess receptor activator of NF-κβ (RANK) ligand surface expression on circulating leucocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines and OC differentiation assays were performed. RESULTS: Classical activation markers of monocytes and RANK increased in patients with RA at baseline, compared with control healthy donors, and after MTX and low-dose PDN (MTX+PDN) exposure they decreased to control levels. Although the number of OC was not different between groups, the percentage of resorbed area and the resorbed area per pit reduced after treatment. Serum soluble receptor activator of nuclear factor-kappa (RANKL) levels increased at baseline compared with healthy donors and normalised after therapy. CONCLUSION: Our results suggest that MTX+PDN play an important role in downregulating OC function, which we believe occurs through the decrease in RANK surface expression in monocytes.