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ID PMID Title PublicationDate abstract
29231492 [Literature study for acupoint selection rule of rheumatoid arthritis treated with acupunc 2017 Feb 12 To explore the clinical acupoint selection rule of rheumatoid arthritis(RA) treated with acupuncture by literature analysis. The related articles were retrieved in 6 Chinese and English databases,including CNKI,VIP,WANFANG,PubMed,Medline and Cochrane. We established a holistic acupoint database and a disease location acupoint database. The results show that there are 120 acupuncture prescriptions and 143 acupoints,with the highest frequency of Zusanli(ST 36). Local acupoints are mainly used for disease locations. The highest acupoin-tcombination frequency of 32 for mandibular joint shows Kunlun(BL 60) and Jiexi(ST 41);22 for finger joint,Baxie(EX-UE 9) and Zusanli(ST 36);28 for wrist joint,Yangxi(LI 5) and Yangchi(TE 4);24 for elbow joint,Quchi(LI 11) and Zusanli(ST 36);21 for shoulder joint,Jianyu(LI 15) and Zusanli(ST 36);13 for spine joint,Yaoyangguan(GV 3) and Shenzhu(GV 12);18 for hip joint,Zhibian(BL 54) and Huantiao(GB 30);20 for knee joint,Shenshu(BL 23) and Yanglingquan(GB 34);32 for ankle joint,Kunlun(BL 60) and Jiexi(ST 41);22 for toe joint,Baxie(EX-UE 9) and Zusanli(ST 36);25 for whole body joints,Yanglingquan(GB 34) and Zusanli(ST 36). Thirty new acupoint prescriptions are found by entropy clustering analysis for different disease regions induced by RA. There exists the acupoint selection rule for acupuncture treating RA and the new prescriptions need to be clinical verification.
28662439 Interleukin-20 is triggered by TLR ligands and associates with disease activity in patient 2017 Sep BACKGROUND: Interleukin (IL)-20 is a pro-inflammatory cytokine that may be implicated in the pathogenesis of rheumatoid arthritis (RA). This study aimed to determine the association between IL-20 and disease activity in patients with RA. METHODS: The levels of serum and synovial fluid IL-20 were measured in patients with RA and OA. The disease activity was assessed based on the Disease Activity Score of 28 joints (DAS28). The expression of IL-20 in synovial tissue samples from patients with RA and OA were determined by immunohistochemistry. Immunofluorescence staining was used to co-localize IL-20 with selected cells. The secretion of IL-20 was analysed in human peripheral blood mononuclear cells (PBMCs) of patients with RA. RESULTS: Synovial fluid and synovial tissue IL-20 were significantly increased in patients with RA compared with patients with OA. The expression of IL-20 in RA synovial tissue was particularly associated with macrophages and neutrophil granulocytes, but also with synovial fibroblasts and lymphocytes. The IL-20 levels in synovial fluid correlated with DAS28 (r=0.434; p=0.015) and were significantly elevated in anti-CCP positive RA compared with anti-CCP negative RA (122.3±104.1pg/ml and 45.9±35.8pg/ml; p=0.008). IL-20 production from PBMCs was induced by Poly I:C and LPS but not with pro-inflammatory cytokines, such as TNF-α or IL-1. CONCLUSION: Our data showed that IL-20 is independently associated with RA disease activity and may be triggered by TLR ligands at local sites of inflammation.
27777170 Rheumatoid arthritis, insulin resistance, and diabetes. 2017 Jul Recent progress in the management of rheumatoid arthritis (RA) is turning attention toward comorbidities, such as diabetes. The objectives of this review are to clarify the links between RA and diabetes and to assess potential effects of disease-modifying antirheumatic drugs (DMARDs) on diabetes. The increased insulin resistance seen in RA is closely linked to the systemic inflammation induced by certain proinflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-6. The prevalence of type 2 diabetes is increased in patients with RA. Furthermore, certain DMARDs including hydroxychloroquine, methotrexate, TNFα antagonist, and interleukin-1β antagonists seem to improve the markers of glucose metabolism. In contrast, glucocorticoids tend to adversely affect glycemic control, particularly when taken chronically. Consequently, a crucial yet insufficiently applied rule is that cardiovascular risk factors must be sought and treated routinely, particularly as the choice of the DMARD may affect glucose metabolism.
28884308 Spa therapy adjunct to pharmacotherapy is beneficial in rheumatoid arthritis: a crossover 2018 Feb This study aims to investigate whether 2-week spa therapy, as an adjunct to usual pharmacological therapy, has any beneficial effect in patients with rheumatoid arthritis (RA). In this single-blind crossover study, 50 patients were randomly assigned in a 1:1 manner to receive usual pharmacological therapy plus 2-week spa therapy or usual pharmacological therapy alone (period 1.6 months); after a 9-month washout, patients were crossed over to the opposite assignment (period 2.6 months). Spa therapy program included a daily saline balneotherapy session at 36-37 °C for 20 min except Sundays. The clinical outcomes were evaluated at baseline, after spa therapy (2 weeks) and 3 and 6 months after the spa therapy in both period and were pain (Visual Analogue Scale (VAS)), patient and physician global assessments (VAS), Health Assessment Questionnaire (HAQ), and Disease Activity Score (DAS28). Spa therapy was superior to control therapy in improving all the assessed clinical outcomes at the end of the spa therapy. This superiority persisted significantly in physician global assessment (p = 0.010) and with a trend in favor of spa group in patient global assessment (p = 0.058), function (p = 0.092), and disease activity (p = 0.098) at 3 months. Statistically significant improvements were found in spa therapy compared to control in disease activity (p = 0.006) and patient (p = 0.020) and physician global (p = 0.011) assessments, and a trend toward improvements in pain (p = 0.069) and swollen joints (p = 0.070) at 6 months. A 2-week spa therapy adjunct to usual pharmacological therapy provided beneficial clinical effects compared to usual pharmacological therapy alone, in RA patients treated with traditional disease-modifying antirheumatic drugs. These beneficial effects may last for 6 months.
28959861 [IL-6: the next key target for rheumatoid arthritis after TNF-α]. 2017 Jan 25 IL-6 is an important cytokine that plays an important role in the pathogenesis of rheumatoid arthritis. We summarized the clinical efficacy and safety of tocilizumab, the IL-6 receptor monoclonal antibody in rheumatoid arthritis, and compared tocilizumab with TNF-α blocking mAbs. The efficiency of tocilizuamb is equivalent to that of TNF-α blockers, and each of the drugs has its advantages and disadvantages. We also summarized the clinical trials of the mAbs blocking IL-6 pathway in development. According to the results of recent studies by several research teams including our research group, IL-6 is another key target for the treatment of rheumatoid arthritis after TNF-α. The listing of the IL-6 blockers provides more choices for personalized treatment of rheumatoid arthritis in the future.
28089976 Disease Characteristics and Rheumatoid Arthritis Development in Patients with Early Undiff 2017 Feb OBJECTIVE: To examine the 2-year disease course in patients with undifferentiated arthritis (UA) focusing on fulfillment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria. METHODS: Data were provided by the Norwegian Very Early Arthritis Clinic study, which included patients presenting with ≥ 1 swollen joint of ≤ 16 weeks' duration. UA was defined as patients not fulfilling the 2010 ACR/EULAR RA criteria and who did not have a clinical diagnosis other than RA at baseline. The main outcome was fulfillment of the 2010 RA criteria. Secondary outcomes were disease-modifying antirheumatic drug (DMARD) use, resolution of synovitis without use of DMARD during followup, and final clinical diagnosis. RESULTS: We included 477 patients with UA of whom 47 fulfilled the 2010 ACR/EULAR RA criteria during followup (UA-RA) and 430 did not (UA-non-RA). Of the UA-RA patients, 70% fulfilled the criteria within the first 6 months. UA-RA patients were older, more often positive for rheumatoid factor and anticitrullinated protein antibodies, female, and ever smokers, and they more often presented with polyarticular arthritis, small joint involvement, and a swollen shoulder joint. During followup, 53% of UA-RA patients vs 13% of UA-non-RA patients used DMARD (p < 0.001). Overall, 71% of patients with UA achieved absence of clinical synovitis at final followup without use of DMARD. The most frequent final clinical diagnosis was UA (61%). CONCLUSION: Only 9.8% of patients with UA fulfilled the 2010 RA criteria during 2-year followup. Small joint involvement and swollen shoulder joint were among the factors associated with RA development. In two-thirds of patients with UA, the arthritis resolved without use of DMARD.
29235264 Reconceptualizing motivation for smoking cessation among people with rheumatoid arthritis 2018 Mar OBJECTIVES: Smokers with rheumatoid arthritis (RA) may have different motivations for, and barriers to, quitting. Understanding the motivations of smokers and ex-smokers with RA will help in the design and implementation of targeted smoking cessation interventions for people with RA that are not based solely on extrapolation from the general population or populations with other chronic illnesses. METHODS: Twenty-nine smokers and 10 recent ex-smokers with RA participated in semi-structured interviews via telephone 18 months after being offered a smoking cessation intervention in Aotearoa/New Zealand. The sample consisted of 27 women and 12 men (age range 32-78 years), of whom 14 had received the intervention, 14 had been in the control group and 11 had declined participation in the trial. RESULTS: Thematic analysis led to the formulation of four "incentives" to quit and five "facilitators" of quitting for people with RA. Desiring improvements to health (overall and specific to arthritis), social relationships and avoiding costs were incentives to quit. Coping with stress without smoking, commitment, mental preparedness, willpower and interventions were facilitators of quitting. CONCLUSIONS: Becoming aware of the effects of smoking on arthritis provides an important motivation to quit smoking that may counter RA-specific barriers to smoking cessation. Further research is needed to test whether similar incentives and facilitators of smoking cessation exist in other chronic illnesses, and how to develop interventions to address these motivational processes.
29023518 Factors associated with the risk of gingival disease in patients with rheumatoid arthritis 2017 Gingival disase and rheumatoid arthritis (RA) are linked at both the epidemiologic and pathogenesis levels. In this study, we aimed to identify environmental factors associated with RA and gingival disease and to investigate factors that protect the gingival tissue in RA patients. This retrospective study analyzed 754 RA patients with gingival disease selected from the NHANES database who completed the mobile examination center interview/examination between 1999 and 2004. Data collected included demographics, lifestyle, dietary intake, and biomarkers. The study included 173 RA patients with gingival disease. Multivariate logistic regression analysis showed that the odds of gingival disease were significantly increased with male gender. However, the odds of gingival disease was significantly decreased with increased vitamin C intake (OR = 0.996, p = 0.041), and higher serum vitamin D levels (OR = 0.979, p = 0.011). Given the significant association between the prevalence of gingival disease and RA, identification of risk factors of gingival disease will be useful as a screening tool in national health surveys to improve the management of periodontal disease in patients with RA.
28611082 A population-based cohort study of rheumatoid arthritis-associated interstitial lung disea 2017 Oct OBJECTIVES: To compare mortality risks in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and patients with RA without ILD. DESIGN: Matched cohort study. SETTING: The study was conducted in Denmark, using nationwide, prospectively collected data. PARTICIPANTS: Among patients with RA diagnosed between 2004 and 2016, 679 patients with RA-ILD were matched for birth year, gender and age at RA diagnosis with 11 722 patients with RA but without ILD. MAIN OUTCOME MEASURES: Mortality risks were assessed using Kaplan-Meier mortality curves, and hazard rate ratios (HRRs) for death were estimated using Cox proportional hazards regression models. RESULTS: The number of prevalent RA patients more than doubled from 15 352 to 35 362 individuals during the study period. RA-ILD was seen in 2.2% of incident RA patients. 34.0% of RA-ILD cases were diagnosed within 1 year prior to and 1 year after the RA diagnosis. One-year mortality was 13.9% (95% CI, 11.4% to 16.7%) in RA-ILD and 3.8% (95% CI, 3.5% to 4.2%) in non-ILD RA, 5-year mortality was 39.0% (34.4% to 43.5%) and 18.2% (17.3% to 19.1%) and 10-year mortality was 60.1% (52.9% to 66.5%) and 34.5% (32.8% to 36.1%), respectively. The HRRs for death were 2 to 10 times increased for RA-ILD compared with non-ILD RA, irrespective of follow-up period. Stratified analysis showed that the HRR for death was highest in the first months after the diagnosis of RA-ILD was made, especially in patients diagnosed with RA before diagnosis of ILD. HRR was higher in males and in patients without comorbidity as assessed by the Charlson Comorbidity Index. CONCLUSIONS: ILD is a serious complication in RA, with a significantly increased mortality compared with a large matched cohort of RA comparisons without ILD.
27565000 Tofacitinib in Combination With Conventional Disease-Modifying Antirheumatic Drugs in Pati 2017 Apr OBJECTIVE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared patient-reported outcomes (PROs) in patients with RA treated with tofacitinib or placebo in combination with conventional disease-modifying antirheumatic drugs (DMARDs). METHODS: In a 12-month, phase III randomized controlled trial (ORAL Sync), patients (n = 795) with active RA and previous inadequate response to therapy with ≥1 conventional or biologic DMARD were randomized 4:4:1:1 to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, placebo advanced to 5 mg BID, or placebo to 10 mg BID, in combination with stable background DMARD therapy. PROs included patient global assessment of arthritis (PtGA), patient assessment of arthritis pain (Pain), physical function (Health Assessment Questionnaire disability index [HAQ DI]), health-related quality of life (Short Form 36 health survey [SF-36]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), and sleep (Medical Outcomes Study Sleep [MOS Sleep]). RESULTS: At month 3, statistically significant improvements from baseline versus placebo were reported in PtGA, Pain, HAQ DI, all 8 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 10 mg BID, and in PtGA, Pain, HAQ DI, 7 SF-36 domains, FACIT-F, and MOS Sleep with tofacitinib 5 mg BID. Improvements were sustained to month 12. Significantly more tofacitinib-treated patients reported improvements of greater than or equal to the minimum clinically important differences at month 3 versus placebo in all PROs, except the SF-36 role-emotional domain (significant for tofacitinib 10 mg BID). CONCLUSION: Patients with active RA treated with tofacitinib combined with background conventional DMARD therapy reported sustained, significant, and clinically meaningful improvements in PROs versus placebo.
29071988 [Review on Modern Repair Mechanism of Moxibustion for Treating Inflammatory Damage of Rheu 2017 Jun 25 Rheumatoid arthritis (RA) is a chronic inflammatory disease. Persistent inflammation of the synovial membrane is the main characteristic pathological symptom. Moxibustion for treating RA has achieved significant clinical effect in recent years. A large number of experimental studies have also shown that moxibustion promoted the repair of inflammatory damage induced by RA. Based on summarizing 10 years related literatures, the authors analyzed the repair mechanisms of moxibustion for inflammatory damage in RA from central mechanisms including glucocorticoid receptor, melatonine, hypothalamic-pituitary-adrenal axis, and cholinergic nerve to peripheral mechanisms including local inflammatory mediators, cytokine, and inflammatory cell signaling pathway, so as to provide evidences and reference for further research.
28215392 The clinical outcomes of atlanto-axial arthrodesis in patients with rheumatoid arthritis - 2017 May PURPOSE: The purpose of this study was to evaluate the clinical outcomes of atlanto-axial arthrodesis in rheumatoid arthritis (RA) patients with cervical myelopathy using the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). METHODS: Twenty patients who underwent surgery to treat atlanto-axial subluxation (AAS) were reviewed. RESULTS: The rates of success rates for each domain were as follows: cervical spine function, 11 of 18 patients (61.1%); upper extremity function, 3 of 15 patients (20%); lower extremity function, 8 of 18 patients (44.4%); bladder function, 5 of 13 patients (38.5%); and quality of life, 3 of 20 patients (15%). Significant differences of success rate were found between the following domains: cervical spine function and upper extremity function, cervical spine function and the quality of life, and lower-extremity function and quality of life. There were significant differences in the pre- and post-surgery visual analogue scale (VAS) scores for pain or stiffness in the neck or shoulders, and pain or numbness in the arms and hands. CONCLUSION: Atlanto-axial arthrodesis in RA patients provided a better outcome for cervical spine function, with improvement in VAS scores for pain or stiffness in the neck or shoulders. This surgery provided improvement of pain or numbness of the upper extremities but not of upper-extremity function. In contrast, the surgery achieved a relatively good recovery in lower-extremity function but little improvement of pain or numbness of the lower extremities. The success rate with regard to quality of life was found to be significantly lower than the success rates observed for cervical spine function and lower-extremity function.
26179634 Ulcerative keratitis in patients with rheumatoid arthritis in the modern biologic era: a s 2017 Feb AIM: To assess the prevalence, clinical characteristics, treatment, and outcomes of patients who developed ulcerative keratitis (UK) during the course of rheumatoid arthritis (RA) in the modern biologic era. METHOD: We retrospectively reviewed the medical records of 589 patients with RA who visited our department between April 2003 and October 2014, and identified patients who developed UK. We also obtained data about clinical characteristics of RA and UK, complications, treatment, and both visual and life prognoses of these patients. RESULTS: Among 589 patients with RA, eight patients (1.4%) were diagnosed with UK. The mean age at the onset of RA was 61.0 years, while the mean age at the onset of UK was 73.0 years. Most of the patients were seropositive and had established RA with a relatively low disease activity. Secondary Sjögren's syndrome was observed in two patients. Peripheral UK occurred as a complication of scleritis, while central UK was not associated with scleritis. Although the mean duration of follow-up was only 3.7 years, visual and life prognoses were both tolerable with therapy, including the use of topical and systemic corticosteroids and calcineurin inhibitors, sometimes combined with biologic disease-modifying antirheumatic drugs (DMARDs) and corneal transplantation. CONCLUSION: This retrospective study demonstrated that the prevalence of UK in patients with RA was 1.4%. Immediate combination therapy, including topical and systemic corticosteroids and calcineurin inhibitors, together with biologic DMARDs and corneal transplantation, was effective for treating RA patients who developed UK in the modern biologic era.
28102843 IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovia 2017 Jan 19 Fibroblast-like synoviocytes (FLSs) are a major cell population of the pannus that invades cartilage and bone in rheumatoid arthritis (RA). FLS resistance to apoptosis is a major characteristic of RA. The aims of this study were to investigate the effects of interleukin-17 (IL-17) and IL-17-producing T helper (Th17) cells on resistance to apoptosis in FLSs from RA patients (RA FLSs) and their roles in mitochondrial dysfunction and autophagy. Mitochondrial function was assessed in RA FLSs and FLSs from osteoarthritis patients (OA FLSs). FLSs were treated with IL-17 and their morphological features, respiratory level and mitochondrial gene expression were measured. The effects of IL-17 and Th17 cells on the relationship between autophagy and apoptosis were evaluated by measuring the expression of apoptosis-related genes using sodium nitroprusside or 3-methyladenine. The mitochondria of FLSs isolated from RA and osteoarthritis patients displayed different morphological and physiological features. RA FLSs exhibited greater autophagosome formation and greater dysfunction of mitochondrial respiration compared with OA FLSs. IL-17 induced mitochondrial dysfunction and autophagosome formation in RA FLSs, suggesting that they were resistant to apoptosis. Autophagy-related antiapoptosis induced by IL-17 was restored by inhibition of autophagy, suggesting a relationship between mitochondrial dysfunction and cell survival in RA FLSs. Th17 cells and IL-17 increased autophagy of RA FLSs by causing mitochondrial dysfunction. Our findings suggest that, in RA, interactions between RA FLSs and Th17 cells may be involved in the tumorous growth of FLSs and the formation of pannus in joints.
27369647 Ultrasound can be useful to predict an evolution towards rheumatoid arthritis in patients 2017 May INTRODUCTION: Ultrasound (US) subclinical synovitis in prerheumatoid arthritis (RA) patients has been demonstrated in anticitrullinated antibodies (ACPA) positive patients to be predictive for future development of RA. The aim of the study was to assess the value of the US as a predictive factor for the future development of RA in patients with polyarthralgia without ACPA. METHOD: Eighty consecutive ACPA-patients with polyarthralgia without clinical synovitis or ACPA before the US examination were included. To detect significant US synovitis, we applied the criteria of a US score (SONAR) validated among RA patients and controls. The diagnosis of RA was based on the ACR/EULAR criteria. RESULTS: Significant US synovitis were present at baseline in 20 (25%) of the patients. The mean (SD) follow-up time was 18 (7) months in both groups. Seven (9%) patients developed a clear RA and 2 another inflammatory arthritis. US synovitis at baseline was significantly associated with evolution to RA: 5/20 (25%) versus 2/60 (3%) (P<0.05). The free time to RA was significantly shorter when US synovitis were present (P<0.01). Moreover, after multivariate analysis, US appeared to be the only independent predictor of an evolution to RA (OR: 7.4). Results remained similar after including all patients developing another inflammatory arthritis. CONCLUSIONS: Our study suggests that US can be used as a predictor for the evolution to RA or other inflammatory arthritis in patients presenting polyarthralgia without ACPA.
28927869 What have we learned from BeSt? 2018 Jan BACKGROUND: How have the long term outcomes of RA improved in the last decade? METHODS: Patients with DMARD naïve RA were randomized to 4 treatment strategies: 1. sequential DMARD monotherapy, 2. step-up combination therapy, 3. initial combination therapy including prednisone or 4. including infliximab. Treatment-to-target was aimed at DAS≤2.4 (three-monthly calculations). Functional ability (HAQ), radiologic damage progression (Sharp/vanderHeijde Score) and overall survival were reported. RESULTS: Patients in arms 3 and 4 showed earlier clinical improvement. Up to 50% achieved DAS-remission (<1.6), up to 29% achieved drug free remission. Damage progression was well suppressed (median after 10years in completers 2 SHS points), functional ability approached normality (mean HAQ 0.6). There was no increased mortality (Standardized Mortality Ratio 1.16, 95% CI 0.92-1.46). CONCLUSIONS: Early treatment determines early clinical improvement, treatment-to-target determines long term outcomes. Prevention of relevant radiologic damage progression and disability, drug free remission and normalized survival are realistic goals.
27908302 Rituximab increases peripheral natural killer cells in patients with rheumatoid arthritis. 2017 Mar OBJECTIVES: The clinical response of rituximab (RTX) is related to the degree of B cell depletion, although other circulating lymphocytes may be affected. We investigated the changes in lymphocyte sub-populations in rheumatoid arthritis (RA) patients treated with RTX and their relationship with the therapeutic response, with attention to natural killer (NK) cells. METHODS: In fifty-one RA patients peripheral blood B and T lymphocytes and NK cells subtypes were counted by flow cytometry before and 3, 6 and 12 months after RTX administration. Patients were evaluated for disease activity with DAS28-CRP and EULAR response criteria at each visit. RESULTS: RTX significantly increased from baseline values CD56+3- cells (28 %, 19 % and 25 %; p<0.001, p=0.009 and p=0.004 respectively for month 3, 6 and 12) and CD56dimCD16+ cells (41%, 24% and 36%; p<0.001, p=0.001 and p<0.001 respectively for month 3, 6 and 12). CD56bri16- cells were unaffected by RTX treatment. The increase in both CD56+3- and CD56dimCD16+ cells was significantly greater in patients who were re-treated with another course of RTX at month 6 (p=0.046 and p=0.010 respectively). An inverse correlation between disease activity score and increase in NK cells was demonstrated. No significant changes were observed in CD3+, CD4+ and CD8+ cells during the whole observation period. CONCLUSIONS: In RA patients, RTX treatment is associated with significant and persistent increase in CD56+3- and CD56dimCD16+ NK cells. A correlation with disease activity is probable, although the association with clinical response remains to be proved.
27829535 A critical role of transcription factor YY1 in rheumatoid arthritis by regulation of inter 2017 Feb Previous studies have revealed a critical role of YY1, a "Yin Yang" transcription factor, in cancer development and progression. However, whether YY1 has any role in rheumatoid arthritis (RA) remains unknown. This study aims to explore the potential role of YY1 in RA pathogenesis. In this study, we found that YY1 was over-expressed in RA patients and CIA mice. Blocking of YY1 action with YY1 shRNA lentivirus ameliorated disease progression in CIA mice. We further analyzed the signaling pathway involved by ingenuity pathway analysis (IPA), results showed IL-6 signaling and JAK/Stat signaling pathway was significantly inhibited by LV-YY1-shRNA treatment. Moreover, we observed that blocking of YY1 reduced IL-6 production and downregulated Th17 population. Finally, we showed YY1 positively regulated IL-6 transcription by binding to the promoter region of the IL-6 gene. In conclusion, YY1 plays a critical role in promoting IL-6 transcription in RA which contribute to the inflammation of RA via stimulation of Th17 differentiation. Thus, YY1 is likely a key molecule involved in the inflammation process of RA. Targeting of YY1 may be a novel therapeutic strategy for RA.
28551592 Heterogeneity of the cytokinome in undifferentiated arthritis progressing to rheumatoid ar 2017 Sep OBJECTIVES: To conduct a comprehensive analysis of cytokine concentrations in sera and mononuclear cell supernatants in order to examine inter- and intra-individual cytokine variations in undifferentiated arthritis progressing to rheumatoid arthritis and healthy control groups. METHODS: Patients with UA (undifferentiated arthritis) developing RA (rheumatoid arthritis) (UA→RA) (n=16) and healthy controls (n=16) were enrolled into the study. UA→RA patients were followed up for six months since the final RA diagnosis. Cytokines IFN-γ, IL-10, TNF, IL-17A, IL-6, IL-1β, IL-2 in sera and mononuclear cell supernatants in 72h and 120h culture variants with- and without anti-CD3 stimulations were assayed using flow cytometric bead array. RESULTS: The cytokine profile of UA→RA differs from the healthy individual cytokine profile. It is possible to observe specific cytokine pattern characterizing each patient, which alters during course of disease. Specifically, we can distinguish three UA→RA cohorts: the group of patients susceptible to the therapy, characterized by the drop of cytokine levels between 1st and 3rd visit with visible decrease of cytokines in 2nd visit and then secondary slighter increase in 3rd visit; the group of patients refractory or clinically worsening on the therapy, characterized by the highest cytokine levels at 2nd visit with secondary decrease in 3rd visit; and the group of patients with variable responses to the therapy without any specific common cytokine pattern. The cytokine patterns in supernatants of PBMC stimulated anti-CD3 for 72h and 120h are very similar. CONCLUSIONS: The personal profile including multiplexed cytokine patterns in serum and supernatant may be potentially used for optimization of therapy introduction and monitoring.
29063462 The role of microalbuminuria as a predictor of subclinical cardiovascular events in rheuma 2018 Mar Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects many body tissues and leads to major morbidity and mortality. Renal disease in RA is clinically important because it restricts the management of primary disease and increases mortality. The objectives of this study are to (1) investigate the difference between RA patients with and without microalbuminuria (MAU) and (2) find out the relation between MAU and disease activity as well as subclinical cardiovascular effects. Ninety RA patients were divided into two groups according to the presence of MAU, in addition to 30 healthy volunteers. ESR, hs-CRP, RF, lipid profile, urinary microalbumin, GFR, renal function tests, carotid intima media thickness (cIMT), flow-mediated dilatation of the brachial artery (FMD), ECG, and echocardiographic examination were performed for patients and controls. MAU positive RA patients revealed significantly higher lipid profile, ESR, hs-CRP, DAS 28, cIMT, and lower FMD as well as ECG and echocardiographic abnormalities compared to MAU negative RA patients. Moreover, there was significant positive correlation between MAU and DAS28, hs-CRP, LDL, cIMT as well as negative correlation with FMD%. In our study, all RA patients with MAU had a normal serum creatinine concentration and gave a negative result with Albustix. MAU is significantly correlated with ESR, hs-CRP, lipid profile, cIMT, and FMD% in RA patients; therefore, it can be used as an index to measure disease activity as well as subclinical cardiovascular affection in RA patients.