RA患者血栓前状态标志物的变化及意义

目的：探讨类风湿关节炎（RA）患者血栓前状态标志物的变化及意义。方法：采用ELISA测定84例RA患者的血浆凝血酶-抗凝血酶复合物（TAT）、纤维蛋白肽A（FPA）、蛋白C（PC）、血管性血友病因子（vWF）、P-选择素（P-Selectin）、血栓前体蛋白（TpP）、D-二聚体（D-D）含量,以70名健康体检者作为对照组。所有患者进行手和腕关节X线等检查,按美国风湿病学会（ARA）标准进行X线分期。结果：与对照组相比,RA患者组血浆TpP、TAT、vWF、FPA、P-选择素、D-D显著升高（均P〈0.05）,PC显著下降（均P〈0.01）,且随期别的增加而增加或降低（除Ⅲ期与Ⅳ比较外）,均具有显著的统计学意义（均P〈0.05）,活动组（PC除外）与非活动组间比较有显著性差异（均P〈0.05）。结论：RA患者存在血栓前状态标志物明显异常,提示存在血栓前状态,应积极予以防范,以免血栓栓塞事件的发生。     

RANTES Gene Polymorphisms Are Not Associated with Rheumatoid Arthritis and Atopic Dermatitis: A Meta-Analysis

Background: A few recent studies have suggested that regulated on activation, normal T cell expressed and secreted (RANTES) polymorphisms (-403 G/A, -28C/G) are associated with rheumatoid arthritis (RA) and atopic dermatitis (AD). However, there still existed studies that did not confirm this correlation. Objective: The objective of this study was to evaluate the relationships of RANTES and RA and AD using a meta-analysis. Methods: Pubmed, Embase, and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers, and pooled odds ratio (OR) with 95% confidence interval (CI) were calculated. Results: Eight studies were enrolled, including a total of 548 RA cases and 493 controls of -403G/A, 305 RA cases and 303 controls of -28C/G, and 705 AD cases and 578 controls of -403G/A in this meta-analysis. In RA, the overall OR and 95% CI of -403A were 1.41, 1.10–1.82 (p = 0.391) and 2.18, 1.30–3.66 (p = 0.335) in dominant and recessive models, respectively. The overall OR and 95% CI of -28G in RA were 1.35, 0.91–2.01 (p = 0.707) and 3.32, 1.29–8.52 (p = 0.559) in dominant and recessive models, respectively. Moreover, the overall OR and 95% CI of -403A in AD were 1.38, 1.08–1.76 (p = 0.421) and 1.06 and 0.65–1.72 (p = 0.361) in dominant and recessive models, respectively. Conclusions: This meta-analysis showed that RANTES -403G/A and -28C/G were not associated with RA and AD.     

RF、AKA和抗CCP抗体联检对类风湿关节炎诊断的临床价值

目的:探讨类风湿因子(Rheum atoid factor,RF)、抗角质蛋白抗体(antikeratin antibody,AKA)及抗环瓜氨酸肽(anti-cyc lic c itru llinated peptide,CCP)抗体对类风湿关节炎(rheum atoid arthritis,RA)的临床意义和早期应用价值。方法:对40例类风湿关节炎患者、30例系统性红斑狼疮和30名正常健康体检者进行RF、AKA、抗CCP抗体检测,应用速率散射比浊法测定RF,间接免疫荧光法检测AKA,ELISA法测定抗CCP抗体。结果:40例RA患者血清中,RF灵敏度和特异性分别为70.0%、90.0%,AKA灵敏度和特异性分别为35.0%、96.7%,抗CCP抗体灵敏度和特异性分别为85.0%、93.3%,联检RF、AKA及抗CCP抗体灵敏度和特异性分别为97.07%、99.8%。结论:RF、AKA和抗CCP抗体可作为诊断RA比较特异的血清学指标,三项指标联检可在一定程度上弥补RF对RA的诊断不足,提高RA的阳性诊断率,且有助于疾病的预后判断。     

Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to Rheumatoid Arthritis: A Meta-Analysis

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.     

类风湿性关节炎患者IL-6、IL-18和CRP的水平变化及意义

目的：研究类风湿性关节炎（RA）患者血清白细胞介素-6（IL-6）、白细胞介素-18（IL-18）和C-反应蛋白（CRP）水平的变化及其临床意义。方法：收集84例RA患者,以70例健康体检者作对照。采用双抗体夹心酶联免疫吸附法测定血清IL-6、IL-18和免疫荧光法测定CRP的水平,并测定血小板计数（Plt）、血沉（ESR）、类风湿因子（RF）。结果：RA患者的血清Plt、ESR、RF、IL-6、IL-18和CRP的含量明显高于健康对照组（P〈0.01）。RA患者活动期上述指标含量（除RF外）均显著高于稳定期（P〈0.01）,Plt升高RA患者组与Plt正常组相比,RF、ESR、IL-6、IL-18和CRP水平均有明显统计学差异（P〈0.05）。结论：IL-6、IL-18和CRP在RA患者的疾病发展过程中发挥着重要作用,它们的水平变化与RA患者病情有关,联合动态监测有助于临床观察RA患者的病情变化和治疗效果。     

Serum Pro-hepcidin Levels in Rheumatoid Arthritis and Systemic Lupus Erythematosus

Hepcidin is a principal iron regulatory hormone and its expression is stimulated by cytokines. The aim of this study was to determine serum levels of the prohormone form of hepcidin, pro-hepcidin, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The study included 72 RA and 28 SLE patients and 33 healthy controls (HC). Serum iron status, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and pro-hepcidin levels were determined. Pro-hepcidin levels in the RA group was higher than SLE and HC groups (p < 0.05, p < 0.001, respectively). Pro-hepcidin levels did not correlate with disease activity scores, cytokine levels and serum iron status in the RA and SLE groups, while it correlated with TNF-alpha, IL-6 and ferritin levels in the HC group (r = 0.459, p < 0.01, r = 0.374, p < 0.05, r = -0.603, p < 0.01, respectively). Pro-hepcidin levels show extremely wide variations within the groups as do iron status and cytokines. Despite these wide variations correlation analysis do not reveal anything.     

Ghrelin and Obestatin Levels in Rheumatoid Arthritis

Background: Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients. Design: Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet’s disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay. Results: Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (p < 0.05 for both), but when compared with HC group differences were not significant. There was no difference across groups in terms of acylated ghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-α in the HC group (r = 0.400, p < 0.05; r = 0.412, p < 0.05, r = 0.543, p < 0.01 and r = 0.528, p < 0.05, respectively). Conclusions: Our results did not show a significant correlation between circulating ghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.     

抗环瓜氨酸肽抗体检测对类风湿关节炎的临床诊断价值

目的探讨抗环瓜氨酸肽抗体（抗CCP抗体）检测对类风湿关节炎（RA）诊断的意义。方法采用酶联免疫吸附试验（ELISA）检测115份人血清的抗CCP抗体,同时采用免疫透射比浊法定量检测类风湿因子（RF）,包括40例RA患者,45例其它风湿病患者,30名正常人;并分析抗CCP抗体与RF实验结果之间的相关性。结果在40例RA病人中,抗CCP抗体的阳性率为80.0%,在其它风湿病人中的阳性率为7.0%,抗CCP抗体对RA的敏感性和特异性分别为80.0%、96.0%,其敏感性高于RF,但差异无统计学意义（P〉0.05）,特异性明显高于RF（P〈0.05）。联合应用抗CCP抗体与RF进行诊断,二者均阳性时敏感性为65.0%,特异性为97.3%。抗CCP抗体与RF实验结果之间无相关性。结论抗CCP抗体对RA具有较好的敏感性和很高的特异性,可与RF相互补充,联合检测可提高对RA早期诊断的准确性。     

Benefit-Finding Among Patients with Rheumatoid Arthritis: Positive Effects on Interpersonal Relationships

This longitudinal study of patients with rheumatoid arthritis used mixed methods to identify and describe the positive effects of illness on relationships, examine correlates of benefit-finding, and test the relationship between benefit-finding and adjustment outcomes. When asked about interpersonal benefits of their illness, 71.3% of the respondents described interpersonal benefits, whereas 16.2% reported another type of benefit, and 12.5% reported no benefits. The most frequently described benefit was appreciation of support received from loved ones. Less pain, lower psychological distress, and perceiving fewer social constraints were related to finding interpersonal benefits in the illness experience. Interpersonal benefit-finding predicted lower levels of disability at a 12-month follow-up. Findings are discussed with regard to conceptual issues, methodological recommendations, and implications for interventions.     

Immunoelectronmicroscopic Characterization of Intracellular Inclusions in Synovial Fluid Cells of Patients with Rheumatoid Arthritis

Qualitative immunoelectronmicroscopic (IEM) analysis of intracellular inclusions in synovial fluid (SF) cells in rheumatoid arthritis (RA) was performed using the peroxidase-antiperoxidase (PAP) method. Cells from patients with chronic RA were fixed in glutaral-dehyde containing 0.05% saponin to permeabilize membranes before immunologic treatments. Intracellular inclusions of IgG, IgM, and C3 were observed in vacuoles of greater than 75% of both polymorpho-nuclear leukocytes (PMNs) and mononuclear phago-cytic cells. IgA-and fibrinogen-containing inclusions were less frequent. Intracellular staining for albumin was minimal. Other membranous, vesicular, and granular unstained materials of potential importance were also often present in the same vacuoles. Stained inclusions were clearly distinct from lipid bodies, which were negative for immunostaining. Control samples had only occasional, scattered and weak stain that was easily recognizable as nonspecific and thus established the specificity of the reactions. A few lymphocytes in 2 patients showed positive staining for IgG in vacuoles. Extracellular staining of clumps of immunoglobulins, C3, and fibrinogen was also present. The various materials phagocytized by the different SF cells may be important in perpetuation of joint inflammation.     

甲状腺机能亢进症患者血清骨钙素变化的研究

为探讨甲状腺机能亢进症时 ,高甲状腺激素水平对血清骨钙素的影响 ,本文对 87例甲状腺机能亢进患者及 5 2名健康志愿者采用放射免疫法测定了血清骨钙素 (OC)、FT3、FT4 和TSH。结果显示 :健康志愿者血清骨钙素水平随着年龄的增高而逐渐降低 ;男女性别间经统计学处理无显著性差异 (P >0 .0 5 )。各年龄组甲亢患者治疗前OC浓度明显升高 (P <0 .0 0 1) ,经抗甲状腺药物治疗甲亢症状缓解后 ,血清OC浓度也降至正常 ;相关统计分析表明 ,甲亢治疗前、后血清OC与FT3、FT4 之间呈明显的正相关 (FT3:r =0 .84- 0 .2 7　P <0 .0 1;FT4 :r=0 .5 8- 0 .2 9　P <0 .0 1) ;与TSH无相关性。结论 :甲状腺激素可能直接参与加速骨转换过程 ,并以增加骨吸收过程为显著 ,导致骨量丢失 ;提示血清OC可以作为甲亢所致骨代谢改变的诊断及其疗效观察的敏感指标之一。     

IgE Anti-IgG Antibodies in Patients with Juvenile and Adult Rheumatoid Arthritis Including Felty's Syndrome

Anti-IgG; antihodies (anti-IgG) of the IgE class were studied in sera from patients with juvenile rheumatoid arthritis (JRA). rheumatoid arthritis (RA) and patients with Felty's syndrome (FS) by use of an indirect immunofluorescence technique. Forty-two percent of 26 patients with JRA had IgE anti-IgG in serum all in low titers. Positive reactions prevailed in patients with multiple joint involvement. Sixty-three percent of 30 patients with RA and 80% of 20 patients with FS had IgE anti-IgG, the titers found in FS patients being significantly higher. In JRA and FS patients the IgE anti-IgG titers were correlated to the titers of anti-IgG of the IgG class, and for FS patients also with the IgM and IgA classes of anti-IgG. In six of 10 patients with RA the synovial fluid samples from both knees contained IgE anti-IgG. In four of these patients the titers of IgE anti-IgG were higher than in the corresponding serum sample, pointing to a local production. After G-200 Sephadex chromatography IgE anti-IgG were demonstrated in the void volume indicating the presence of these autoantibodies in immune complexes. IgE anti-IgG may be involved in the pathogenesis of JRA and RA by eliciting Type I and III reactions.     

血清中葡萄糖6-磷酸异构酶在类风湿关节炎中的诊断价值

目的探讨血清中葡萄糖6-磷酸异构酶（glucose-6-phosphate isomerase，GPI）抗原在类风湿关节炎（rheumatoid arthritis，RA）患者诊断中的意义。方法用酶联免疫吸附试验（ELISA）检测70例RA患者，26例其他风湿病患者和30例健康对照血清中GPI抗原的浓度，RA患者同时还检测了类风湿因子（RF）。结果70例RA患者血清中GPI浓度为（2．01±1．01）μg／mL，26例其他风湿性疾病组为（0．41±0．18）μg／mL，30例健康对照组为（0．090±0．030）μg／mL，RA患者血清中GPI浓度显著高于其他风湿病组和健康对照组（P〈0．01），在RA活动组和RA非活动组。亦有显著差异（P〈0．05）。通过分段回归分析发现GPI的浓度和RA病情活动成正相关。GPI抗原对RA检测的敏感性为61．4％．特异性为93．3％。结论GPI在部分RA患者血清中显著升高，有可能成为诊断RA及判断其疾病活动性的一个新指标。     

葡萄糖-6-磷酸异构酶对类风湿关节炎诊断价值的系统评价

为了评价血清中葡萄糖-6-磷酸异构酶(glucose-6-phosphate isomerase,GPI)诊断类风湿关节炎(rheumatoidarthritis,RA)的价值,检索1990~2007年相关数据库,关于酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清中GPI诊断RA的诊断性试验文献,提取四格表资料,利用RevMan软件分析。15个研究对GPI检测异质性较大:χ2=191.65,P0.00001,使用已知浓度血清作为标准品的5篇文献,具有同质性(χ2=6.97,P=0.14),合并OR=1.93(95%CI:1.40,2.67),有效性检验Z=4.00(P0.0001)。15个研究合并诊断敏感性为38%,合并特异性为87%,曲线下面积为0.7846;5个使用相同标准品的研究合并诊断敏感性为25%,合并特异性为80%,曲线下面积为0.6279。GPI在RA诊断中的特异性较高而敏感性较差,可与高敏感性的其他标志物联合检测。     

Endometrial Osteopontin mRNA Expression and Plasma Osteopontin Levels are Increased in Patients with Endometriosis

Problem  The aim of this study was to evaluate osteopontin (OPN) mRNA expression in eutopic endometrium and plasma OPN levels in patients with endometriosis.
Method of study  A total of 79 patients with histologically confirmed endometriosis and 43 patients without endometriosis participated in this study. OPN mRNA expression in endometrial tissues was measured by real-time quantitative polymerase chain reaction (PCR) and plasma concentrations of OPN were quantified using a specific commercial sandwich enzyme-linked immunosorbent assays (ELISA).
Results  Osteopontin mRNA expression in endometrial tissue was significantly higher in women with endometriosis than in controls ( P =  0.010). The mean plasma levels of OPN (mean ± S.E.M.) in patients with endometriosis and controls were 407.31 ± 37.80 ng/mL and 165.84 ± 19.29 ng/mL, respectively ( P  < 0.001). Receiver operating characteristic (ROC) analysis for plasma OPN revealed an area under the curve (AUC) of 0.894, with a sensitivity of 93.0%, specificity of 72.4%, positive likelihood ratio of 3.37, and negative likelihood ratio of 0.1 using a cut-off value of 167.68 ng/mL.
Conclusion  Osteopontin may be involved in the pathogenesis of endometriosis and plasma OPN may be a useful non-invasive marker for the diagnosis of endometriosis.     

Chemokine Signaling Pathway Involved in CCL2 Expression in Patients with Rheumatoid Arthritis

Purpose

Rheumatoid arthritis (RA) is an inflammatory joint disorder, the progression of which leads to the destruction of cartilage and bone. Chemokines are involved in RA pathogenesis. In this study, we investigated the chemokine signaling pathway associated with CCL2 in peripheral blood (PB) and synovial tissues (ST) of RA patients based on our previous work about chemokine signaling pathway involved in the activation of CCL2 production in collagen-induced arthritis rat ST.

Materials and Methods

Total RNA was isolated from PB leukocytes and synovium of the knee joint in both RA patients and control populations. Real-time polymerase chain reaction was used to determine CCL4, CCR5, c-Jun, c-Fos, and CCL2 expressions. Serum level of CCL2 was assessed by enzyme-linked immunosorbent assay, and the production of CCL2 in ST was analyzed immunohistochemically.

Results

The expressions of CCL4, CCR5, c-Jun, c-Fos, and CCL2 messenger RNA in RA patients were significantly higher than those in healthy controls, both in ST and on PB leukocyte. Serum CCL2 levels were elevated in RA patients. Histological examination of rheumatoid joints revealed extensive CCL2 expression in RA ST.

Conclusion

CCL2, CCL4, c-Jun, c-Fos, and CCR5 may play an important role in the recruitment of PB leukocytes into the RA joints. These data provide evidence that the chemokine signaling pathway is involved in CCL2 expression in RA patient tissues, which may contribute to chronic inflammation associated with RA. Targeting this signaling pathway may provide a novel therapeutic avenue in RA.     

Interleukin-4 Cellular Gene Therapy and Osteoprotegerin Decrease Inflammation-Associated Bone Resorption in Collagen-Induced Arthritis

To evaluate the respective action of IL-4, an anti-inflammatory cytokine, and OPG, an inhibitor of bone resorption, on the inflammatory process and the associated bone resorption in collagen-induced arthritis (CIA). After CIA induction, DBA/1 mice were treated with OPG or with IL-4 DBA/1 transfected fibroblasts or both OPG + IL-4. CIA significantly improved in IL-4 groups. OPG had no effect on arthritis clinical scores but histologic scores were reduced in OPG, IL-4, and OPG + IL-4 groups vs. nontreated CIA mice. OPG increased significantly BMD and decreased by 45% D-pyridinolin levels. Moreover association of IL-4 and OPG exerted an additive effect of BMD and resorption marker (-68%). Production of IFN-gamma in the supernatants of spleen cells was reduced in IL-4 treated mice. OPG had a moderate effect on IFN-gamma, but potentiated the inhibitory effect of IL-4. OPG and IL-4 prevent bone loss in CIA-mice model and could have additive effects on IFN-gamma secretion.     

类风湿性关节炎患者血清TNF-α和外周血B细胞及T细胞亚群的探讨

目的：探讨了类风湿性关节炎患者血清TNF—α和外周血B淋巴细胞及T淋巴细胞亚群水平的变化。方法：分别应用放射免疫分析和单克隆技术测定了37例类风湿性关节炎患者血清TNF—α,和外周血B淋巴细胞及T淋巴细胞亚群的水平，并以30名正常健康人作比较。结果：类风湿性关节炎患者血清TNF—α和外周血B淋巴细胞数显著地高于正常人水平（P〈0．01），而CD3、CD4、CD4／CD8则显著地低于正常人水平（P〈0．01）。结论：类风湿性关节炎是一种自身调节免疫异常的疾病。     

Immunomodulatory Effect of Nigella sativa Oil on T Lymphocytes in Patients with Rheumatoid Arthritis

Background and objectives: Abundant evidence indicates the involvement of CD4⁺, CD8⁺, and CD4⁺CD25⁺ T lymphocytes in the induction and/or protection of rheumatoid arthritis (RA). We aimed to investigate the modulatory effect of Nigella sativa (NS) oil on the selected T cell subset percentage in females with RA.

Methods: A randomized, double-blinded placebo-controlled, 2 months, parallel-group clinical trial was conducted. Forty-three female patients (20–50 years) with mild to moderate RA were recruited and assigned into NS (n = 23) and placebo (n = 20) groups to receive one gram of NS oil, or starch, capsule in two divided doses, respectively. The disease activity scores of 28 joints (DAS28) were calculated and percentages of CD4⁺, CD8⁺, and CD4⁺CD25⁺ T cells were examined using flow cytometry.

Results: Treatment with NS led to significant reduction of the serum high-sensitivity C-reactive protein (hs-CRP) level and DAS-28 score and an improved number of swollen joints compared with baseline and placebo groups. A relatively comparable CD4⁺ T cell percentage was observed in the NS and placebo groups either in baseline or the end of study. The treatment also resulted in reduced CD8⁺, and increased CD4⁺CD25⁺ T cell percentage and the CD4⁺/CD8⁺ ratio as compared to placebo and baseline. A negative significant correlation between changes in CD8⁺ and changes in CD4⁺CD25⁺ T cells and a positive significant correlation between changes in CD4⁺CD25⁺ T cells and changes in the CD4⁺/CD8⁺ ratio was observed in the NS group.

Conclusion: This study gives strength to the potential relevance of NS in clinical management of RA through modulation of T lymphocytes.