Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid arthritis in a genetically homogeneous population

Rheumatoid arthritis (RA) is a multifactorial disease that is increasing in incidence worldwide. It is associated with a complex mode of inheritance, with many genes being involved in the development and progression of the disease. Genome-wide association studies in different populations have recently revealed a significant association between a TRAF1/C5 and a STAT4 polymorphism and the development of RA. In the present study we performed a case-control study in the population of the island of Crete, Greece, aiming to replicate the former findings in a genetically homogeneous cohort of patients. We found that mutated allele A or genotypes A/A and G/A of the TRAF1/C5 rs10818488 SNP were more common in individuals with RA than in control individuals (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.35-2.15, and OR = 2.22, 95% CI = 1.61-3.05, respectively). Similarly, mutated allele T or genotypes T/T and G/T of the STAT4 rs7574865 SNP were also associated with susceptibility to RA (OR = 1.9, 95% CI = 1.46-2.50, and OR = 2.37, 95% CI 1.73-2.25, respectively). Thus, we conclude that mutant alleles or genotypes of both polymorphisms examined are associated with the development of RA in our population.     

Mutual antagonistic relationship between prostaglandin E(2) and IFN-gamma: Implications for rheumatoid arthritis

Prostaglandin E(2) (PGE(2)) is a major mediator of inflammation and is present at high concentrations in the synovial fluid of rheumatoid arthritis (RA) patients. PGE(2), acting through the EP4 receptor, has both pro- and anti-inflammatory roles in vivo. To shed light on this dual role of PGE(2), we investigated its effects in whole blood and in primary human fibroblast-like synoviocytes (FLS). Gene expression analysis in human leukocytes, confirmed at the protein level, revealed an EP4-dependent inhibition of the expression of genes involved in the IFN-gamma-activation pathway, including IFN-gamma itself. This effect of the PGE(2)/EP4 axis on IFN-gamma is a reciprocal phenomenon since IFN-gamma blocks PGE(2) release and blocks EP receptor expression. The mutually antagonistic relationship between IFN-gamma and PGE(2) extends to downstream cytokine and chemokine release; PGE(2) counters the effects of IFN-gamma, on the release of IP-10, IL-8, TNF-alpha and IL-1beta. To gain further insight into IFN-gamma-mediated cellular events in RA, we assessed the effects of IFN-gamma on gene expression in FLS. We observed an IFN-gamma-dependent up-regulation of macrophage-attracting chemokines, and down-regulation of metalloprotease expression. These results suggest the existence of a mutually antagonistic relationship between PGE(2) and IFN-gamma, which may represent a fundamental mechanism of immune control in diseases such as RA.     

The role of physical activity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease, causing progressive damage to the musculoskeletal system. Many patients with RA also suffer from accelerated muscle loss or cachexia, which contributes to the loss of physical function and quality of life. Physical activity plays a central role in the management of the disease as it is essential to maintain muscle strength and endurance, range of motion and the ability to perform activities of daily life. On the other hand, given the nature of the disease, there is always an increased risk for injury. There is a large amount of literature investigating the effect of exercise interventions on muscle function and disease activity. These studies show that exercise clearly improves muscle function without affecting disease activity. Studies including radiographic evaluation of joint damage as an endpoint also show that there is no evidence that exercise, even high-intensity exercise, increases inflammation or joint damage, although care should be taken with patients with severe baseline damage. Regarding daily physical activity (exercise is only one component of physical activity) there is hardly any research done showing either that physical activity is indeed decreased in patients or whether or not there is a relation between daily physical activity and disease activity. The results from studies looking at the effect of exercise on muscle mass or the ability to prevent or reverse cachexia are somewhat contradictory, but it seems that when the training dose is sufficiently large, gains in muscle mass can be achieved.     

The contribution of pain and depression to self-reported sleep disturbance in patients with rheumatoid arthritis

The objective of this article is to assess the contribution of disease activity, pain, and psychological factors to self-reported sleep disturbance in patients with rheumatoid arthritis (RA), and to evaluate whether depression mediates the effects of pain on sleep disturbance. The sample included 106 patients with confirmed RA who participated in an assessment of their disease activity, pain, psychological functioning, and sleep disturbance during a baseline evaluation prior to participating in a prospective study to help them manage their RA. Self-measures included the Rapid Assessment of Disease Activity in Rheumatology, the SF-36 Pain Scale, the Helplessness and Internality Subscales of the Arthritis Helplessness Index, the Active and Passive Pain Coping Scales of the Pain Management Inventory, the Center for Epidemiological Studies Depression Scale, and the Pittsburgh Sleep Quality Index. Hierarchical multiple regression analysis confirmed that higher income, pain, internality, and depression contributed independently to higher sleep disturbance. A mediational analysis demonstrated that depression acted as a significant mechanism through which pain contributed to sleep disturbance. Cross-sectional findings indicate that pain and depression play significant roles in self-reported sleep disturbance among patients with RA. The data suggest the importance of interventions that target pain and depression to improve sleep in this medical condition.     

Pre-miR-146a基因rs2910164位点单核苷酸基因多态性及miR-146a表达与类风湿关节炎相关性研究

目的 探讨pre-miR-146a基因rs2910164位点单核苷酸基因多态性及miR-146a表达与类风湿关节炎相关性.方法 采用聚合酶链反应-连接酶检测反应检测123例类风湿关节炎(RA)患者和220例健康对照者pre-miR-146a rs2910164位点基因多态性,应用实时荧光定量聚合酶链反应检测68例RA患者、10例骨关节炎(OA)患者及20例健康对照外周血单个核细胞中miR-146a的表达水平,并选取10例RA疾病活动患者行激素加免疫抑制剂正规治疗3个月后miR-146a表达水平的测定.收集并计算RA患者临床参数:发病年龄、性别、类风湿因子(RF)和抗环瓜氨酸肽(抗-CCP)抗体、RA疾病活动(DAS28≥3.2)、骨破坏(X＞Ⅰ期).统计学处理采用X2检验、方差分析、t检验和Pearson相关分析.结果 RA组pre-miR-146a rs2910164位点的基因型频率和等位基因频率与健康对照组比较,差异无统计学意义(P均＞0.05).RA患者pre-miR-146ars2910164位点基因型与发病年龄、性别、RF和抗-CCP抗体阳性率、RA疾病活动、骨破坏阳性率及miR-146a表达量均无相关性(P均＞0.05).RA患者组miR-146a的表达量高于健康对照组和OA组(P均＜0.01),后两组miR-146a的表达量无统计学差异(P＞0.05).RA疾病活动组miR-146a表达高于非活动组和对照组(P均＜0.01),后两组miR-146a的表达量无统计学差异(P＞0.05).RA疾病活动患者治疗后miR-146a表达下降(P＜0.05),DAS28评分降低(P＜0.01).RA患者组miR-146a的表达与红细胞沉降率(ESR,即血沉)、C反应蛋白(CRP)及DAS28评分之间呈正相关(P均＜0.01),与RF、抗-CCP抗体滴度无相关性(P均＞0.05).结论 我国汉族人群中,pre-miR-146a rs2910164位点多态性与RA的易感性、临床参数及miR-146a的表达无相关性,RA患者外周血单个核细胞miR-146a表达上调,其表达水平与RA病情活动有关,miR-146a的检测可能是RA病情活动的一个有用的判断指标.     

Multifaceted activities of CCR7 regulate T-cell homeostasis in health and disease

CCR7 is a homeostatically expressed chemokine receptor that is known to regulate the homing of various types of immune cells to primary, secondary, and tertiary lymphoid organs. Recent evidence suggests that, in addition to controlling cell migration, CCR7-mediated signals affect T-cell homeostasis in lymph nodes at various levels and also influence T-cell activation and polarization. In this review, we highlight these findings and discuss recently proposed functions of the CCR7 pathway in the induction and maintenance of chronic inflammation.     

Integration of complementary and alternative medicine in primary care: What do patients want?

Objective

To explore patients’ perspectives towards integration of Complementary and Alternative Medicine (CAM) in primary care.

Methods

A mixed-methods approach was used. This included a survey on use, attitudes and disclosure of CAM, an e-panel consultation and focus group among patients with joint diseases.

Results

A total of 416 patients responded to the survey who suffered from osteoarthritis (51%), rheumatoid arthritis (29%) or fibromyalgia (24%). Prevalence of CAM use was 86%, of which 71% visited a CAM practitioner. Manual therapies, acupuncture and homeopathy were most frequently used. A minority (30%) actively communicated CAM use with their General Practitioner (GP). The majority (92%) preferred a GP who informed about CAM, 70% a GP who referred to CAM, and 42% wanted GPs to collaborate with CAM practitioners. Similar attitudes were found in the focus group and upon e-panel consultation.

Conclusions

Most patients in primary care want a GP who listens, inquires about CAM and if necessary refers to or collaborates with CAM practitioners.

Practice implications

To meet needs of patients, primary care disease management would benefit from an active involvement of GPs concerning CAM communication/referral. This study presents a model addressing the role of patients and GPs within such an integrative approach.     

类风湿性关节炎:膝关节高频超声及超声造影表现与实验室检查的相关性

目的探讨类风湿性关节炎(RA)膝关节滑膜改变的高频超声及CEUS表现与实验室检查的相关性。方法对72例RA患者及30名正常人行高频超声及彩色多普勒超声观察滑膜状态(包括滑膜厚度、关节积液程度、滑膜血流情况);应用CEUS观察膝关节滑膜微循环情况,并分析其与抗环瓜氨酸肽抗体(Anti-ccp)、类风湿因子(RF)、血沉(ESR)、C-反应蛋白(CRP)的相关性。结果超声示,与正常人比较,RA患者膝关节出现不同程度的滑膜增厚、关节积液增多(P<0.01);CEUS更为清晰地显示滑膜内血管翳形成情况;滑膜厚度与CRP(r=0.36,P<0.001)及ESR(r=0.49,P<0.001)、膝关节髌上囊液体厚度与CRP(r=0.44,P<0.001)及ESR(r=0.52,P<0.001)、滑膜厚度与Anti-ccp均有一定相关性(r=0.44,P=0.033)。结论 RA的高频超声及CEUS表现与实验室检查具有相关性,可在一定程度上为诊断RA提供依据。     

中西医结合护理对活动期类风湿关节炎患者康复质量的影响

目的:探讨中西医结合护理对活动期类风湿关节炎(RA)患者康复质量的影响.方法:将120例活动期RA患者随机分为观察组和对照组各60例.对照组给予常规护理,观察组在此基础上给予中西医结合护理.比较两组患者临床症状改善情况、护理满意度及住院时间.结果:两组临床症状改善、护理满意度及住院时间比较差异均有统计学意义(P<0.05).结论:中西医结合护理可提高活动期RA患者的康复治疗效果及护理满意度,改善生活质量,值得推广应用.