Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
26436849 Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to R 2015 OBJECTIVE: Association of matrix metalloproteinases (MMPs) gene polymorphisms with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify this dispute. METHODS: We systematically searched the electronic PUBMED, EMBASE and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9) gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to the heterogeneity, fixed-effects or random-effects models were used to calculate crude odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: A total of 11 articles involving 2143 cases and 2049 controls were included in this meta-analysis. Overall, no significant associations were observed between MMP-1-1607 1G/2G polymorphism and RA. Stratification by ethnicity, no significant associations were observed in Caucasian populations. Similarly, no significant associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms and RA in overall and Caucasian populations, respectively. However, a weak association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR = 0.813, 95%CI = 0.694-0.953, p = 0.010) in overall populations. CONCLUSIONS: The present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP-2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with more sample size are needed for definitive conclusions.
25956924 Utility of a novel inflammatory marker, GlycA, for assessment of rheumatoid arthritis dise 2015 May 9 INTRODUCTION: GlycA is a novel inflammatory biomarker measured using nuclear magnetic resonance (NMR). Its NMR signal primarily represents glycosylated acute phase proteins. GlycA was associated with inflammation and development of cardiovascular disease in initially healthy women. We hypothesized that GlycA is a biomarker of disease activity and is associated with coronary artery atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: We conducted a cross-sectional study of 166 patients with RA and 90 control subjects. GlycA was measured from an NMR signal originating from N-acetylglucosamine residues on circulating glycoproteins. The relationship between GlycA and RA disease activity (Disease Activity Score based on 28 joints (DAS28)) and coronary artery calcium score was determined. RESULTS: GlycA concentrations were higher in patients with RA (median (interquartile range): 398 μmol/L (348 to 473 μmol/L)) than control subjects (344 μmol/L (314 to 403 μmol/L) (P < 0.001). In RA, GlycA was strongly correlated with DAS28 based on erythrocyte sedimentation rate (DAS28-ESR) and DAS28 based on C-reactive protein (DAS28-CRP) and their components, including tender and swollen joint counts, global health score, ESR and CRP (all P < 0.001). The area under the receiver operating characteristic curve for GlycA's ability to differentiate between patients with low versus moderate to high disease activity based on DAS28-CRP was 0.75 (95% confidence interval (CI): 0.68, 0.83). For each quartile increase in GlycA, the odds of having coronary artery calcium increased by 48% (95% CI: 4%, 111%), independent of age, race and sex (P = 0.03). CONCLUSION: GlycA is a novel inflammatory marker that may be useful for assessment of disease activity and is associated with coronary artery atherosclerosis in patients with RA.
26606398 Association of Triple Therapy With Improvement in Cholesterol Profiles Over Two-Year Follo 2016 Mar OBJECTIVE: To evaluate long-term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial. METHODS: Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time. RESULTS: Mixed-effect models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level, or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups (P < 0.001-0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol (P < 0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2-year followup. CONCLUSION: Decreases in RA disease activity over long-term followup were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during 2 years of followup was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. Additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.
27995997 TIARP attenuates autoantibody-mediated arthritis via the suppression of neutrophil migrati 2016 Dec 20 TNFα-induced adipose-related protein (TIARP) is a six-transmembrane protein expressed on macrophages, neutrophils and synoviocytes. We reported recently that mice deficient in TIARP (TIARP(-/-)) spontaneously develop arthritis and are highly susceptible to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effects of TIARP on neutrophils and fibroblast-like synoviocytes (FLS) have not been elucidated. We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP(-/-) mice. Arthritis in TIARP(-/-) mice transferred with K/BxN serum was significantly exacerbated compared with WT mice. We characterized the differences in neutrophils between wild-type (WT) and TIARP(-/-) mice by DNA microarray. Overexpression of CXCR1 and CXCR2 was noted in TIARP(-/-) neutrophils. Neutrophils of TIARP(-/-) mice showed strong migration activity, which was markedly facilitated by CXCL2 in vitro and in vivo. Moreover, enhanced production of CXCL2 and IL-6 and cell proliferation was noted in TIARP(-/-) TNFα-stimulated FLS. Blockade of IL-6R significantly attenuated serum-transferred TIARP(-/-) arthritis with diminished neutrophil recruitment in joints. Our findings suggested that TIARP independently down-regulated CXCL2 and IL-6 production by FLS, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, with resultant reduction of neutrophil migration into arthritic joints.
27270893 Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RI 2016 Jun 27 The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA). Adalimumab bound to monocyte membrane TNF from RA patients and unexpectedly enhanced its expression and its binding to TNF-RII expressed on T reg cells. As a consequence, adalimumab expanded functional Foxp3(+) T reg cells equipped to suppress Th17 cells through an IL-2/STAT5-dependent mechanism. Our data not only highlight the beneficial effect of membrane TNF on T reg cell numbers during chronic inflammation, but in addition reveal how a therapeutic antibody that is thought to act by simply blocking its target can enhance the regulatory properties of this proinflammatory cytokine.
26262880 Increased Risk of Acute Pancreatitis in Patients with Rheumatoid Arthritis: A Population-B 2015 The study was conducted to determine whether patients with rheumatoid arthritis (RA) are at increased risk of acute pancreatitis compared with those without RA and to determine if the risk of acute pancreatitis varied by anti-RA drug use. We used the large population-based dataset from the National Health Insurance (NHI) program in Taiwan to conduct a retrospective cohort study. Patients newly diagnosed with RA between 2000 and 2011 were referred to as the RA group. The comparator non-RA group was matched with propensity score, using age and sex, in the same time period. We presented the incidence density by 100,000 person-years. The propensity score and all variables were analyzed in fully adjusted Cox proportional hazard regression. The cumulative incidence of acute pancreatitis was assessed by Kaplan-Meier analysis, with significance based on the log-rank test. From claims data of one million enrollees randomly sampled from the Taiwan NHI database, 29,755 adults with RA were identified and 119,020 non-RA persons were matched as a comparison group. The RA cohort had higher incidence density of acute pancreatitis (185.7 versus 119.0 per 100,000 person-years) than the non-RA cohort. The adjusted hazard ratio (HR) was 1.62 (95% CI [confidence interval] 1.43-1.83) for patients with RA to develop acute pancreatitis. Oral corticosteroid use decreased the risk of acute pancreatitis (adjusted HR 0.83, 95% CI 0.73-0.94) but without a dose-dependent effect. Current use of disease modifying anti-rheumatic drugs or tumor necrosis factor blockers did not decrease the risk of acute pancreatitis. In conclusion, patients with RA are at an elevated risk of acute pancreatitis. Use of oral corticosteroids may reduce the risk of acute pancreatitis.
26978417 [Correction of an inflammatory process with an interleukin-1 inhibitor in the combination 2015 AIM: To enhance the efficiency of treatment in patients with secondary osteoarthritis (ОА) in the presence of comorbid condition, by using an interleukin-1 inhibitor (IL-1i) and laser therapy (LT). SUBJECTS AND METHODS: A total of 248 patients aged 38 to 65 years with RA and secondary OA who had predominantly Stage II in accordance with the Disease Activity Score 28 (DAS28) were examined. According to the received therapy, the patients were divided into 4 groups: 1) IL-1i + LT + mrthotrexate (MT); 2) IL-1i + MT; 3) LT + MT; 4) MT. The efficiency of treatment was evaluated from changes in the KOOS (Knee injury and Osteoarthritis Outcome Score), DAS 28, IL-1, and cartilage oligomeric matrix protein (COMP) 6 months later. RESULTS: There were statistically significant functional improvements in KOOS and DAS28 in Groups 1 and 2 patients with secondary OA in RA. Clinical efficacy was confirmed by positive changes in serum IL-1 and COMP levels. CONCLUSION: Incorporation of an IL-1i into a therapy regimen for secondary OA in RA patients during basic therapy could not only improve the functional status of patients, but also decrease activity of the underlying disease according to the DAS 28.
27657857 Effects of Koumine on Adjuvant- and Collagen-Induced Arthritis in Rats. 2016 Oct 28 To examine the effect of koumine, a Gelsemium alkaloid, on two experimental models of rheumatoid arthritis (RA), rats with adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) were administered koumine (0.6, 3, or 15 mg/kg/day) or vehicle through gastric gavage (i.g.). Clinical evaluation was performed via measurements of hind paw volume, arthritis index (AI) score, mechanical withdrawal threshold, organ weight, and by radiographic and histological examinations. Levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and antitype II collagen (CII) antibody were also examined. In rats with AIA, koumine reduced the AI score and mechanical allodynia of the injected hind paw in a dose-dependent manner and significantly inhibited increase in thymus and liver weights. In rats with CIA, koumine inhibited increase in hind paw volume, AI score, and mechanical allodynia in a dose-dependent manner and reduced joint space narrowing. Furthermore, koumine also attenuated the increase in the expression of IL-1β and TNF-α, as well as the robust increase of serum anti-CII antibodies in response to immunization. These results suggested that koumine effectively attenuated arthritis progression in two rat models of RA and that this therapeutic effect may be associated with its immunoregulatory action.
26343085 Tenosynovitis US scoring systems follow synovitis and clinical scoring systems in RA and a 2015 Sep AIMS: To investigate by ultrasonography (US) in a cohort of active RA patients starting biologic therapy the responsiveness of tenosynovitis of wrist and hands compared to the responsiveness of synovitis in a 6 month period follow-up, to compare the responsiveness of finger flexor tenosynovitis with the responsiveness of wrist extensor tenosynovitis and to describe the subclinical synovitis and tenosynovitis in RA patients in clinical remission. MATERIAL AND METHODS: Fifty seven patients with active RA starting biologic therapy were included. Clinical, laboratory, and US evaluations were performed at baseline, 1, and 6 months. US evaluation included wrist and MCPs 2-5 joints, bilaterally for synovitis and extensor tendons compartments 2, 4, and 6 and finger flexors 2-5 for tenosynovitis. Eighteen US scores based on semiquantitative or binary grades were calculated at each visit. Responsiveness of synovitis and tenosynovitis scores was calculated using the standardized response mean (SRM). RESULTS: The responsiveness of US tenosynovitis was lower comparing with the responsiveness of US synovitis but both showed large effect of therapy. Furthermore, tenosynovitis responsiveness was similar to CRP responsiveness (SRM -0.90). Finger flexors tenosynovitis showed a higher responsiveness than extensor tenosynovitis on GS (-0.94 compared to -0.63) and a lower SRM on PD (-0.56 compared to -0.85). Tenosynovitis scores remission was overlapping clinical remission according to CDAI and SDAI in 100% of cases. Overall there was less subclinical tenosynovitis than subclinical synovitis at final visit according to clinical activity indices. CONCLUSION: Tenosynovitis US scoring in RA may be as good as synovitis scoring for characterization of disease activity and responsiveness.
27754414 The Inflammatory Role of Platelets: Translational Insights from Experimental Studies of Au 2016 Oct 14 Beyond their indispensable role in hemostasis, platelets have shown to affect the development of inflammatory disorders, as they have been epidemiologically and mechanistically linked to diseases featuring an inflammatory reaction in inflammatory diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disorders. The identification of novel molecular mechanisms linking inflammation and to platelets has highlighted them as new targets for therapeutic interventions. In particular, genetic and pharmacological studies have identified an important role for platelets in neuroinflammation. This review summarizes the main molecular links between platelets and inflammation, focusing on immune regulatory factors, receptors, cellular targets and signaling pathways by which they can amplify inflammatory reactions and that make them potential therapeutic targets.
26670453 Comparison of comorbidities of the Egyptian rheumatoid arthritis patients to the global co 2016 May The aims of this study are to present the results of Egyptian RA patients included in COMORA cohort and compare it to general COMORA cohort, concerning prevalence of comorbidities, and level of application of recommendations related to detection/prevention of comorbidities. Three-hundred eight Egyptian RA patients included in the cross-sectional, observational, multi-center, international study "COMORA", were compared to the total number of 3612 RA patients. The CRF of COMORA was used in all patients. CRF collects demographic and disease characteristics, comorbidities, risk factors, and compliance with recommendations regarding management of comorbidities. Data were analyzed according to COMORA protocol. Egyptian RA patients were significantly younger, had more active disease, and were more functionally disabled. They showed more frequent use of NSAIDs, methotrexate and steroids and significantly lower use of bDMARDs when compared to non-Egyptians. Egyptian patients had the highest ever HCV prevalence, while depression, hypertension, smoking and dyslipidemia were less prevalent in Egyptians. Prevalence of malignancy risk factors was highly deficient among Egyptians; primarily due to lack of screening. Further, following recommendations for monitoring comorbidities is significantly deficient among Egyptian patients. Egyptian patients had more active disease and more functional impairment than the rest of the COMORA cohort; with lower use of bDMARDs, that is possibly related to the economic situation. Also, there is a clear gap in screening and monitoring comorbidities. Awareness among Egyptian healthcare providers (and possibly similar third-world countries) to detect and manage RA-related comorbidities is required.
27627584 Proteome Analysis of Rheumatoid Arthritis Gut Mucosa. 2017 Jan 6 Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5366 proteins. The abundance of dihydrofolate reductase (DHFR) was statistically significantly increased in RA-patient biopsies compared with controls and correlated with the administered dosage of methotrexate (MTX), the most frequently prescribed immunosuppressive drug for RA. Additionally, our data suggest that treatment with Leflunomide, a common alternative to MTX, increases DHFR. The findings were supported by immunohistochemistry with confocal microscopy, which furthermore demonstrated that DHFR was located in the cytosol of the intestinal epithelial and interstitial cells. Finally, we identified 223 citrullinated peptides from 121 proteins. Three of the peptides were unique to RA. The list of citrullinated proteins was enriched in extracellular and membrane proteins and included known targets of anticitrullinated protein antibodies (ACPAs). Our findings support that the colon mucosa could trigger the production of ACPAs, which could contribute to the onset of RA. The MS data have been deposited to ProteomeXchange with identifiers PXD001608 and PXD003082.
24525913 Hypoxia and STAT3 signalling interactions regulate pro-inflammatory pathways in rheumatoid 2015 Jun OBJECTIVE: To examine the effect of hypoxia on Signal Transducer and Activator of Transcription 3 (STAT3)-induced pro-inflammatory pathways in rheumatoid arthritis (RA). METHODS: Detection of phospho-STAT3 was assessed in RA synovial tissue and fibroblasts (RASFC) by immunohistology/immunofluorescence. Primary RASFCs and a normal synoviocyte cell line (K4IM) were cultured under hypoxic and normoxic conditions±Stat3-siRNA, HIF-siRNA or WP1066 (JAK2-inhibitor). HIF1α, p-STAT3, p-STAT1 and Notch-1IC protein expression were analysed by western blot. Functional mechanisms were quantified by invasion chamber, matrigel and migration assays. IL-6, IL-8, IL-10 and matrixmetalloproteinases (MMP)-3 were quantified by ELISA. Notch-1 receptor, its DLL-4 ligand and downstream target genes (hrt-1, hrt-2) were quantified by real-time PCR. The effect of WP1066 on spontaneous secretion of pro/anti-inflammatory cytokines and Notch signalling was examined in RA synovial explants ex vivo. RESULTS: p-STAT3 was increased in RA synovium compared with control (p<0.05). Hypoxia induced p-STAT3, p-STAT1 and HIF1α expression, an effect blocked by Stat3-siRNA and WP1066. Hypoxia-induced cell invasion, migration and cytokine production were inhibited by Stat3-siRNA (p<0.05) and WP1066 (p<0.05). While HIF1α siRNA inhibited hypoxia-induced p-STAT3 detection, Stat3-siRNA also inhibited hypoxia-induced HIF1α. Furthermore, hypoxia-induced Notch-1IC, DLL4, hrt-1 and -2 expression were significantly inhibited by WP1066 (p<0.05). Finally, in RA synovial explant cultures ex vivo, WP1066 decreased spontaneous secretion of IL-6, IL-8 and MMP3 (p<0.05), Notch-1 mRNA (p<0.05) and induced IL-10 (p<0.05). CONCLUSIONS: This is the first study to provide evidence of a functional link between HIF1α, STAT3 and Notch-1 signalling in the regulation of pro-inflammatory mechanisms in RA, and further supports a role for STAT blockade in the treatment of RA.
25044486 Self-perceived oral health and periodontal parameters in chronic periodontitis patients wi 2016 Feb AIM: It is hypothesized that self-perceived oral health and periodontal status are worse in chronic periodontitis (CP) patients with rheumatoid arthritis (RA) compared to CP patients without RA. The aim of the present study was to assess self-perceived oral health and periodontal parameters in CP patients with and without RA. METHODS: Fifty CP patients with RA and 50 CP patients without RA were included. Information regarding sociodemographic characteristics and self-perceived oral symptoms were collected using a questionnaire. Periodontal parameters (plaque index, bleeding on probing, probing depth, clinical attachment loss, number of missing teeth, and marginal bone loss) were recorded. RESULTS: There was no significant difference in socioeconomic status, education status, self-perceived oral symptoms, and periodontal parameters among CP patients with and without RA. CONCLUSIONS: Self-perceived oral health and periodontal parameters are mainly governed by the intensity of CP, and the role of RA in this context seems to be rather secondary.
26036272 Blood-based identification of non-responders to anti-TNF therapy in rheumatoid arthritis. 2015 Jun 3 BACKGROUND: Faced with an increasing number of choices for biologic therapies, rheumatologists have a critical need for better tools to inform rheumatoid arthritis (RA) disease management. The ability to identify patients who are unlikely to respond to first-line biologic anti-TNF therapies prior to their treatment would allow these patients to seek alternative therapies, providing faster relief and avoiding complications of disease. METHODS: We identified a gene expression classifier to predict, pre-treatment, which RA patients are unlikely to respond to the anti-TNF infliximab. The classifier was trained and independently evaluated using four published whole blood gene expression data sets, in which RA patients (n = 116 = 44 + 15 + 30 + 27) were treated with infliximab, and their response assessed 14-16 months post treatment according to the European League Against Rheumatism (EULAR) response criteria. For each patient, prior knowledge was used to group gene expression measurements into disease-relevant biological signaling mechanisms that were used as the input features for regularized logistic regression. RESULTS: The classifier produced a substantial enrichment of non-responders (59 %, given by the cross validated test precision) compared to the full population (27 % non-responders), while identifying nearly a third of non-responders. Given this classifier performance, treatment of predicted non-responders with alternative biologics would decrease their chance of non-response by between a third and a half, substantially improving their odds of effective treatment and stemming further disease progression. The classifier consisted of 18 signaling mechanisms, which together indicated that higher inflammatory signaling mediated by TNF and other cytokines was present pre-treatment in the blood of patients who responded to infliximab treatment. In contrast, non-responders were classified by relatively higher levels of specific metabolic activities in the blood prior to treatment. CONCLUSIONS: We were able to successfully produce a classifier to identify a population of RA patients significantly enriched in anti-TNF non-responders across four different patient cohorts. Additional prospective studies are needed to validate and refine the classifier for clinical use.
26099641 Is there a role for Digital X-ray Radiogrammetry as surrogate marker for radiological prog 2015 Jun 23 INTRODUCTION: The established scoring techniques based on radiographs present limitations in the evaluation of structural integrity due to high effectiveness of innovative therapeutic strategies. The aim of this study was to evaluate the periarticular mineralisation as detected by Digital X-ray Radiogrammetry (DXR) as surrogate marker for structural integrity during the course of rheumatoid arthritis (RA). METHODS: 11 centers throughout Germany contributed data of 94 patients with verified RA. The patients were treated with leflunomide or methotrexate during a mean observation period of 22 months. All patients underwent complete computerized calculations of bone mineral density (BMD) and metacarpal index (MCI) by DXR using digitized hand radiographs. The radiological assessment of disease progression was estimated by the Sharp Score. RESULTS: The Sharp Score revealed no significant change during the study period. DXR-BMD revealed minimal decrease of -1.4 % (leflunomide group) versus a higher reduction of -4.3 % (methotrexate group). Regarding DXR-MCI, a reduction of -2.2 % (leflunomide group) and -4.9 % (methotrexate group) was observed. CONCLUSION: Quantitative data of hand bone mass estimated by the presented DXR-technique may be a complementary precise tool in the identification of RA-related radiographic changes and in the assessment of structural integrity.
26458977 High serum cholesterol predicts rheumatoid arthritis in women, but not in men: a prospecti 2015 Oct 12 INTRODUCTION: Environmental exposures, including smoking, hormone-related factors, and metabolic factors, have been implicated in the etiology of rheumatoid arthritis (RA). A previous study has indicated that blood lipid levels may influence the development of RA. The objective of this study was to investigate the impact of serum total cholesterol and triglycerides on the risk of RA in a prospective study. METHODS: Among participants in a large population-based health survey (n = 33,346), individuals who subsequently developed RA were identified by linkage to four different registers and a structured review of the medical records. In a nested case-control study, with controls, matched for age, sex, and year of inclusion, from the health survey database, the relation between serum lipids (levels of total cholesterol and triglycerides) and future RA development was examined. RESULTS: In total, 290 individuals (151 men and 139 women) whose RA was diagnosed a median of 12 years (range of 1-28) after inclusion in the health survey were compared with 1160 controls. Women with a diagnosis of RA during the follow-up had higher total cholesterol levels at baseline compared with controls: odds ratio (OR) 1.54 per standard deviation; 95 % confidence interval (CI) 1.22-1.94. This association remained statistically significant in multivariate models adjusted for smoking and a history of early menopause and in analyses stratified by rheumatoid factor status and time to RA diagnosis. Total cholesterol had no significant impact on the risk of RA in men (OR 1.03; 95 % CI 0.83-1.26). Triglycerides did not predict RA in men or women. CONCLUSIONS: A high total cholesterol was a risk factor for RA in women but not in men. This suggests that sex-specific exposures modify the impact of lipids on the risk of RA. Hormone-related metabolic pathways may contribute to RA development.
24972750 Meta-analysis of SLC22A4 and RUNX1 polymorphisms : Associations with rheumatoid arthritis 2015 May OBJECTIVE: The aim in this study was to determine whether solute carrier family 22, member 4 (SLC22A4), and runt-related transcription factor 1 (RUNX1) polymorphisms are associated with susceptibility to rheumatoid arthritis (RA) in populations of different ethnicities. METHODS: We conducted a literature search using the MEDLINE and EMBASE, and performed a meta-analysis using a fixed or random effects model. RESULTS: A total of 26 comparative studies from 14 articles met the study inclusion criteria. Studies on the SLC22A4 polymorphism involved 12,458 RA patients and 9283 controls, and studies on the RUNX1 polymorphism involved 3958 RA patients and 3773 controls. The meta-analysis showed no association between the 22 + 21 genotype of the SLC22A4 F1 and RA in overall group [odds ratio (OR) 1.074, 95 % confidence interval (CI) 0.952-1.212, p = 0.245]. After stratification by ethnicity, the meta-analysis indicated that the 22 + 21 genotype of the SLC22A4 F1 was associated significantly with RA in the East Asian population, but not in the European population (OR 1.124, 95 % CI 1.018-1.240, p = 0.021; OR 0.981, 95 % CI 0.773-1.243, p = 0.871). CONCLUSION: This meta-analysis demonstrates that the SLC22A4 F1 polymorphism is associated with susceptibility to RA in East Asians, but not in Europeans.
24722995 PBMC and exosome-derived Hotair is a critical regulator and potent marker for rheumatoid a 2015 Feb Despite growing importance of long non-coding RNAs (lncRNAs) in normal physiological and disease conditions, our knowledge of RA-related lncRNAs remains limited. Therefore, we aimed to identify lncRNA signatures that have prognostic values in RA. There was a notably high expression level of Hotair in blood mononuclear cells and serum exosome of rheumatoid arthritis (RA) patients, leading the migration of active macrophage. In contrast, markedly lower level of Hotair was detected in differentiated osteoclasts and rheumatoid synoviocytes and enforced expression of Hotair led to significantly decreased levels of MMP-2 and MMP-13. This exploratory study provides novel empirical evidence that Hotair could be one of potential biomarkers for diagnosing RA.
25902038 [(18)]F FDG PET/CT imaging to monitor the therapeutic effect of liposome-encapsulated pred 2015 Jul 10 Current treatment of rheumatoid arthritis includes systemic administration of glucocorticoids. To improve joint targeting and anti-inflammatory efficacy these glucocorticoids are encapsulated in long-circulating liposomes. The present study aimed to monitor therapeutic effects of prednisolone (PLP)-containing PEG-liposomes in murine antigen-induced arthritis (AIA) using [(18)F]FDG PET/CT. Mono-articular arthritis was induced in male C57Bl6/J mice. At 0, 3, 7 and 12 days after arthritis induction, inflamed joints were macroscopically scored (0 = unaffected to 4 = immobile) and [(18)F]FDG PET/CT images were acquired. In a second experiment, to study the feasibility to monitor therapeutic effects of PLP encapsulating PEG-liposomes, mice were treated with a single i.v. injection of PLP-containing PEG-liposomes (10 mg/kg) or empty PEG-liposomes 3 days after arthritis induction. Inflamed joints were macroscopically scored and images were acquired at -3, 0, 4 and 9 days after treatment. PET images were analyzed quantitatively, and mice were dissected to allow histological analysis of the joints. With progression of arthritis, [(18)F]FDG uptake in inflamed joints increased significantly (day 0: 2.5 ± 0.9%ID/ml, day 7: 4.4 ± 0.4%ID/ml, p = 0.0159), while no changes were observed in unaffected paws (day 0: 2.5 ± 1.1%ID/ml, day 7: 2.7 ± 0.8%ID/ml, p = 0.3466). In the second experiment, macroscopic scoring revealed suppression of joint swelling after treatment with PLP-containing PEG-liposomes. In line with that, [(18)F]FDG uptake did not change in the treated mice (day -3: 1.9 ± 0.3%ID/ml, day 4: 2.2 ± 0.2%ID/ml, p = 0.3466), while it increased in mice that developed arthritis (day -3: 2.0 ± 0.2%ID/ml, day 4: 3.1 ± 0.6%ID/ml, p = 0.0225). Histological analysis confirmed therapeutic efficacy, which showed less inflammation (p = 0.0354) and bone erosion (p = 0.0298) in treated mice. These data show that [(18)F]FDG PET/CT could be used to monitor the progression of AIA and confirmed rapid and profound anti-inflammatory effects of PLP-containing PEG-liposomes that were also observed macroscopically and microscopically.