Differential Gene Expression in Synovium of Rheumatoid Arthritis and Osteoarthritis

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the major types of arthritis. Although both diseases are characterized by joint destruction, their etiologies are different. To get insights into pathophysiological pathways, we used the suppression subtractive hybridization (SSH) method to identify differentially expressed genes in RA. DNA sequencing identified 12 gene products including cytoskeletal γ-actin and extracellular matrix components such as fibronectin, collagen IIIα₁, and superficial zone protein. Interferon γ-inducible genes such as a novel thiol reductase, two genes of unknown function (HSIFNIN4, RING3), and annexin II were also found. Two genes encoded proteins involved in proliferation such as elongation factor 1α and the granulin precursor. Furthermore, the protease cathepsin B and synovial phospholipase A2 group IIA were detected by SSH. To confirm the differential expression of the genes, we performed RT-PCR analyses of RA and OA synovial tissues. Compared to OA patients, 9 of the 12 genes were overexpressed in RA, suggesting that SSH is a powerful tool for the detection of differential gene expression in synovial tissues. Further characterization of the gene products may help to identify pathophysiological mechanisms in arthritic diseases.     

Associations between APOE Genotypes and Disease Susceptibility,Joint Damage and Lipid Levels in Patients with Rheumatoid Arthritis

Objective

Apolipoprotein E (APOE) genotypes are associated with cardiovascular disease (CVD) and lipid levels. In rheumatoid arthritis (RA), an association has been found with disease activity. We examined the associations between APOE genotypes and disease susceptibility and markers of disease severity in RA, including radiographic joint damage, inflammatory markers, lipid levels and cardiovascular markers.

Method

A Norwegian cohort of 945 RA patients and 988 controls were genotyped for two APOE polymorphisms. We examined longitudinal associations between APOE genotypes and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) as well as hand radiographs (van der Heijde Sharp Score(SHS)) in 207 patients with 10 year longitudinal data. Lipid levels, cardiovascular markers and history of CVD were compared across genotypes in a cross sectional study of 136 patients. Longitudinal radiological data of cohorts from Lund and Leiden were available for replication. (N = 935, with 4799 radiographs).

Results

In the Norwegian cohort, associations between APOE genotypes and total cholesterol (TC) and low-density lipoproteins (LDL) were observed (ε2<ε3/ε3<ε4, p = 0.03 and p = 0.02, respectively). No association was present for acute phase reactant or CVD markers, but a longitudinal linear association between APOE genotypes and radiographic joint damage was observed (p = 0.007). No association between APOE genotypes and the severity of joint destruction was observed in the Lund and Leiden cohorts, and a meta- analysis combining all data was negative.

Conclusion

APOE genotypes are associated with lipid levels in patients with RA, and may contribute to dyslipidemia in some patients. APOE genotypes are not consistently associated with markers of inflammation or joint destruction in RA.     

A Comprehensive Molecular Interaction Map for Rheumatoid Arthritis

Background

Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA).

Methodology

Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA.

Significance

We find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being -at the moment- a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable .xml CellDesigner format at ‘www.picb.ac.cn/ClinicalGenomicNTW/temp.html’ and ‘www.celldesigner.org’.     

类风湿关节炎患者自我效能水平及相关因素分析

目的：探讨类风湿关节炎患者自我效能水平及影响因素,为科学的护理干预提供依据。方法：采用一般自我效能感量表（GSES）对随机抽样的267例类风湿关节炎患者进行调查。测定调查患者的自我效能水平。结果：267例类风湿关节炎患者自我效能水平较低。结论：多种因素影响类风湿患者的自我效能水平,这些影响因素包括：患者文化程度,收入,医疗付费方式,病程等。     

类风湿关节炎患者自我效能水平及相关因素分析

目的:探讨类风湿关节炎患者自我效能水平及影响因素,为科学的护理干预提供依据。方法:采用一般自我效能感量表(GSES)对随机抽样的267例类风湿关节炎患者进行调查,测定调查患者的自我效能水平。结果:267例类风湿关节炎患者自我效能水平较低。结论:多种因素影响类风湿患者的自我效能水平,这些影响因素包括:患者文化程度,收入,医疗付费方式,病程等。     

Increased Reactive Oxygen Species Formation and Oxidative Stress in Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune inflammatory disorder. Highly reactive oxygen free radicals are believed to be involved in the pathogenesis of the disease. In this study, RA patients were sub-grouped depending upon the presence or absence of rheumatoid factor, disease activity score and disease duration. RA Patients (120) and healthy controls (53) were evaluated for the oxidant—antioxidant status by monitoring ROS production, biomarkers of lipid peroxidation, protein oxidation and DNA damage. The level of various enzymatic and non-enzymatic antioxidants was also monitored. Correlation analysis was also performed for analysing the association between ROS and various other parameters.MethodsIntracellular ROS formation, lipid peroxidation (MDA level), protein oxidation (carbonyl level and thiol level) and DNA damage were detected in the blood of RA patients. Antioxidant status was evaluated by FRAP assay, DPPH reduction assay and enzymatic (SOD, catalase, GST, GR) and non-enzymatic (vitamin C and GSH) antioxidants.ResultsRA patients showed a higher ROS production, increased lipid peroxidation, protein oxidation and DNA damage. A significant decline in the ferric reducing ability, DPPH radical quenching ability and the levels of antioxidants has also been observed. Significant correlation has been found between ROS and various other parameters studied.ConclusionRA patients showed a marked increase in ROS formation, lipid peroxidation, protein oxidation, DNA damage and decrease in the activity of antioxidant defence system leading to oxidative stress which may contribute to tissue damage and hence to the chronicity of the disease.     

血清VEGF水平与类风湿性关节患者炎症指标的相关性

目的:研究类风湿性关节炎(RA)患者血清血管内皮生长因子(VEGF)与炎症指标的相关性。方法:随机选取2014年1月至2015年12月我院收治RA患者59例,包括32例RA活动期患者(RA活动期组)与27例RA缓解期患者(RA缓解期组),另抽取同期30例健康体检者作为对照组。应用双抗体夹心酶联免疫吸附法检测三组血清VEGF水平及白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α),用免疫比浊法检测C-反应蛋白(CRP)水平,并采用Pearson相关分析RA患者血清VEGF水平与三项炎性因子之间的相关性。结果:三组血清VEGF以及CRP、IL-6、TNF-α整体比较,差异均有统计学意义(均P0.05),且以上各指标在RA活动期组、RA缓解期组、对照组中依次降低,两两比较差异均有统计学意义(均P0.05)。RA患者的血清VEGF与CRP、IL-6、TNF-α水平均呈正相关关系(r=0.556、r=0.517、0.682,均P0.05)。结论:血清VEGF及CRP、IL-6、TNF-α在RA患者病理改变过程中均表达过度,且VEGF与炎性因子间存在协同相关作用。     

类风湿关节炎患者血脂水平与疾病活动度的相关性研究

目的:观察类风湿关节炎(RA)患者血脂的变化,以及血脂水平与疾病活动度之间的相关性。方法:对71例RA患者和77例正常对照的血脂水平进行回顾性分析,并对RA患者的血脂水平与其疾病活动度进行相关性分析。结果:RA患者的血清总胆固醇(TC)、甘油三酯(TG)水平均高于正常对照组(P0.01),高密度脂蛋白(HDL)水平降低(P0.01)。DAS28评分与TC(r=0.49,P0.01)、TG(r=0.38,P0.01)和LDL(r=0.55,P0.01)呈正相关,与HDL呈负相关(r=-0.57,P0.01),血沉与TC(r=0.26,P=0.03)、TG(r=0.28,P=0.02)呈正相关,C反应蛋白与TC(r=0.65,P0.01)、TG(r=0.30,P=0.01)和LDL(r=0.39,P0.01)均呈正相关。结论:RA患者存在血脂水平异常,且与疾病活动度相关。对血脂进行干预可能改善RA患者的长期预后。     

IGFs and IGF-Binding Proteins in the Synovial Fluid of Patients with Rheumatoid Arthritis and Osteoarthritis

International Journal of Peptide Research and Therapeutics - The progressive damage of human articular cartilage is associated with loss of integrity of its extracellular matrix components. Their...     

A Pilot Study on Zinc Levels in Patients with Rheumatoid Arthritis

The aim of the study was to evaluate zinc levels in three biological compartments (serum, erythrocytes and hair) in patients with rheumatoid arthritis (RA) as compared to healthy individuals. Zinc levels in serum, erythrocytes and hair (in 74 patients with RA and 30 healthy individuals) were assessed by atomic absorption spectroscopy. The mean hair zinc content was significantly lower in RA patients as compared to healthy individuals (p < 0.001). Moreover, a positive correlation was observed in the RA patient group between the erythrocyte zinc levels and the prednisone dose (r _s = 0.48, p < 0.05), and a negative correlation was found in this population between the serum zinc levels and disease duration (r _s = −0.42, p < 0.0006). In conclusion, it seems that hair may be a useful complementary study material for evaluating “zinc status” in rheumatoid arthritis patients.