Low Incidence of Rheumatoid Factor and Autoantibodies in Nigerian Patients with Rheumatoid Arthritis

Sera from 53 Nigerian patients satisfying the American Rheumatism Association criteria for a diagnosis of definite or probable rheumatoid arthritis and sera from sick and healthy Nigerian controls were tested for rheumatoid factor, autoantibodies, and immunoglobulin levels. Rheumatoid factor and autoantibodies were found no more frequently in patients with rheumatoid arthritis than in controls. These findings confirm the clinical impression that Nigerian patients with polyarthritis satisfying the criteria for a diagnosis of rheumatoid arthritis differ from Caucasian patients with the disease in a number of important respects. They suggest that either these patients do not have rheumatoid arthritis but a distinct clinical syndrome or that in Nigeria the course of rheumatoid arthritis is modified by genetic or environmental factors.     

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.     

A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

A_2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A_2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A_2AAR stimulation in a rat model of arthritis. We investigated A_2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A_2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A_2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A_2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A_2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A_2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A_2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A_2AARs in lymphocytes from RA patients. The effectiveness of A_2AAR stimulation in a rat model of arthritis supported the role of A_2AAR agonists as potential pharmacological treatment for RA.     

Risk of Rheumatoid Arthritis in Patients with Type 2 Diabetes: A Nationwide Population-Based Case-Control Study

Objective

Type 2 diabetes is associated with chronic, low-grade inflammation and could potentially trigger the progression of other, more prominent inflammatory diseases such as rheumatoid arthritis (RA). Therefore, we aimed to investigate the risk of incident RA in Taiwanese patients with type 2 diabetes using a population-based health claims database.

Methods

This nationwide, population-based, case-control study used administrative data to identify 1,416 patients with RA (age ≥20 years) as cases and 7,080 controls that were frequency-matched for sex, 10-year age group, and year of catastrophic illness certificate application date (index year). All subjects were retrospectively traced back, up to 13 years prior to the index year, for their first diagnosis of type 2 diabetes. Logistic regression analysis was conducted to quantify the association between incident RA and type 2 diabetes.

Results

The odds of developing RA were significantly higher in female (odds ratio [OR] 1.46, 95% confidence interval [95% CI] 1.24–1.72) but not in male (OR 1.00, 95% CI 0.72–1.37) patients who had previously diagnosed with type 2 diabetes. Subgroup analysis indicated that the odds of developing RA were more prominent in younger females (20 to 44 years of age) with type 2 diabetes. In addition, the odds of developing RA in female patients with type 2 diabetes were higher in those with a shorter time interval between the diagnosis of type 2 diabetes and RA.

Conclusions

This large nationwide, population-based, case-control study showed an elevated risk of RA in female Taiwanese patients with type 2 diabetes. Our findings were consistent with the hypothesis that chronic low-grade inflammation in type 2 diabetes may elicit the development of RA in genetically susceptible individuals.     

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。     

Gelsolin蛋白在类风湿性关节炎和系统性红斑狼疮的临床诊断及疾病活动度评价中的意义

目的:分析gelsolin蛋白对类风湿性关节炎(rheumatoid arthritis,RA)和系统性红斑狼疮(systemic lupus erythematosus,SLE)的临床诊断及疾病活动度评价的意义。方法:采集RA 30名和SLE 47名及健康人群50名的临床资料及血清标本,定量Western Blot法检测血清gelsolin水平。分析gelsolin蛋白与RA和SLE患者临床表现及疾病活动度的相关性。结果:RA、SLE和正常对照组之间性别、年龄、血红蛋白、血小板、血红细胞、血白细胞之间没有显著差异;RA患者出现CRP、转氨酶、RF、CCP异常的阳性率明显高于SLE患者(P0.05);而SLE患者出现白蛋白、尿蛋白、尿红细胞、尿素氮、ANA、肌酐异常增高的几率高于RA患者(P0.05)。gelsolin蛋白在SLE和RA血清中的含量均显著低于正常人(P0.05),且RA患者含量更低(P0.05)。gelsolin蛋白滴度与RA的疾病活动度无明显相关性(r=0.089,P=0.652),而与SLE的疾病活动度呈显著负相关(r=0.646,P0.05)。gelsolin蛋白正常组RA患者的转氨酶升高、CRP、RF、CCP阳性率均显著高于SLE患者(P0.05)。gelsolin蛋白降低组SLE患者的白蛋白、尿蛋白、尿红细胞、尿素氮、ANA、肌酐阳性率显著高于RA患者(P0.05)。结论:gelsolin蛋白滴度检测可作为RA和SLE临床辅助诊断手段,其滴度变化可作为SLE疾病活动度进展的预判指标。     

A Potential Role of Myeloid DAP12-Associating Lectin (MDL)-1 in the Regulation of Inflammation in Rheumatoid Arthritis Patients

The pathogenic roles of myeloid DAP12-associating lectin-1(MDL-1) and DAP12 in human rheumatoid arthritis (RA) remain unknown. Frequencies of MDL-1-expressing monocytes in 22 active RA patients, 16 inactive RA patients, 12 osteoarthritis (OA) patients and 10 healthy controls (HC) were determined by flow-cytometry analysis. The mRNA expression levels of MDL-1 and DAP12 on PBMCs were evaluated by quantitative PCR, and their protein expression levels in the synovium were examined by immunohistochemistry. Significantly higher median percentages of circulating MDL-1-expressing monocytes were observed in active RA patients (53.6%) compared to inactive RA patients (34.1%), OA patients (27.9%), and HC (21.2%). Levels of MDL-1 and DAP12 gene expression in PBMCs and their protein expression in the synovium were significantly higher in active RA patients than in inactive RA or OA patients. MDL-1 levels were positively correlated with parameters of disease activity, articular damage, and levels of proinflammatory cytokines. MDL-1 activator (Dengue virus type 2 antigen) stimulation on PBMCs resulted in significantly enhanced levels of proinflammatory cytokines in RA patients compared to those in OA patients or HC, indicating that MDL-1 activation is functional. Frequencies of MDL-1-expressing monocytes and levels of MDL-1 and DAP12 gene expression significantly decreased after effective therapy. Concordant overexpression of MDL-1 and DAP12 were correlated with increased production of proinflammatory cytokines in RA patients, suggesting their roles in regulating articular inflammation.     

Enhanced Mitochondrial Radical Production in Patients with Rheumatoid Arthritis Correlates with Elevated Levels of Tumor Necrosis Factor alpha in Plasma

Mitochondrial dysfunction contributes to cell damage in a number of human diseases. One significant mechanism by which mitochondria damage cells is by producing reactive oxygen species from the respiratory chain. In this study we measured the production of reactive oxygen species by leukocyte mitochondria in blood from rheumatoid arthritis patients. To do this we used the chemiluminescence of lucigenin, which is accumulated by mitochondria within cells and reacts with superoxide to form a chemiluminescent product. By using specific inhibitors we could distinguish between the production of reactive oxygen species by mitochondria and by NADPH oxidase. There was a five-fold increase in mitochondrial reactive oxygen species production in whole blood and monocytes from patients with rheumatoid arthritis, when compared to healthy subjects or patients with non-rheumatic diseases. There was no increase in mitochondrial reactive oxygen species production by neutrophils from rheumatoid arthritis patients. The enhanced mitochondrial radical production in rheumatoid arthritis patients correlated significantly with increased levels of tumor necrosis factor alpha in plasma (p<0.0001). As tumor necrosis factor alpha is known to increase mitochondrial reactive oxygen species production the elevated mitochondrial radical formation seen in rheumatoid arthritis patients may be due to activation of the mitochondrial radical production. These data suggest that elevated mitochondrial oxidative stress contributes to the pathology of rheumatoid arthritis.     

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。     

Increased Risk of Acute Pancreatitis in Patients with Rheumatoid Arthritis: A Population-Based Cohort Study

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.     

A Comparison of Disease Burden in Rheumatoid Arthritis,Psoriatic Arthritis and Axial Spondyloarthritis

Objective

The main objective of this study was to compare disease burden in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA).

Methods

In this cross-sectional study, all the RA (1093), PsA (365) and ax-SpA (333) patients who visited the out-patient clinic of the Hospital of Southern Norway Trust during the year 2013 were included; the RA patients all had a RA diagnosis verified by the treating rheumatologist, the PsA patients all fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria and the ax-SpA patients all fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for ax-SpA. Patient-reported health status, demographic variables, medications, and composite scores of disease activity were assessed. The main analyses were performed using General Linear Models adjusted for age, sex and multiple comparisons. Correlation analyses were performed using Spearman’s rho.

Results

The reported pain, joint pain, patient’s global assessment and fatigue were similar in PsA and ax-SpA, but significantly lower in RA. The 28-joint Disease Activity Score (DAS28) (0.3±0.1, p = 0.003), Clinical Disease Activity Index (CDAI) (1.0±0.4, p = 0.028) and Routine Assessment of Patient Index Data 3 (RAPID3) (0.4±0.1, p = 0.004) were all significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation with DAS28 (rho = 0.521, p<0.001) and CDAI (rho = 0.768, p<0.001) in RA and PsA, and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (rho = 0.902, p<0.001) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.865, p<0.001) in ax-SpA and PsA.

Conclusion

In conclusion, patient- reported outcome measures were similar in our population of PsA and ax-SpA patients, but significantly lower for the RA patients. Composite disease activity measures were lower in RA than in PsA and ax-SpA, but the magnitude of these differences was small and probably not of clinical significance. Our study indicates that disease burden in RA, PsA and ax-SpA may be more similar than previously demonstrated.     

The Risk of Metabolic Syndrome in Patients with Rheumatoid Arthritis: A Meta-Analysis of Observational Studies

Background

Observational studies suggest an association between the incidence of rheumatoid arthritis (RA) and the prevalence of metabolic syndrome (MetS). However, the relationship between RA and MetS is controversial and research in this area is currently lacking.

Objective

The aim of this study was to assess whether the prevalence of MetS was higher in a group of RA patients compared to subjects without RA.

Design

A PubMed database search was conducted during April 2013 to identify observational studies of RA and risk of MetS. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments, and the method used to control for potential confounding factors. A random-effects model was used for the risk estimates.

Results

Our meta-analysis of four cross-sectional controlled studies plus eight case-control studies involving a total of 2283 cases and 4403 controls identified a significant association between RA and risk of MetS, with an overall OR of 1.24 (95% CI, 1.03-1.50).

Conclusion

This meta-analysis provides further evidence supporting patients with RA have a higher prevalence of MetS than subjects without RA. In addition, the geographic region of the population and the criteria used for MetS diagnosis could influence the association. However, these observations would need to be evaluated using prospective, randomized studies.     

Mannose Binding Lectin and Susceptibility to Rheumatoid Arthritis in Brazilian Patients and Their Relatives

Introduction

Rheumatoid arthritis (RA) is a commonly occurring systemic inflammatory auto immune disease and is believed to be associated with genetic factors. The innate immune complement protein Mannose binding lectin (MBL) and their MBL2 genetic variants are associated with different infectious and autoimmune diseases.

Methods

In a Brazilian cohort, we aim to associate the functional role of circulating MBL serum levels and MBL2 variants in clinically classified patients (n = 196) with rheumatoid arthritis including their relatives (n = 200) and ethnicity matched healthy controls (n = 200). MBL serum levels were measured by ELISA and functional MBL2 variants were genotyped by direct sequencing.

Results

The exon1+54 MBL2*B variant was significantly associated with an increased risk and the reconstructed haplotype MBL2*LYPB was associated with RA susceptibility. Circulating serum MBL levels were observed significantly lower in RA patients compared to their relatives and controls. No significant contribution of MBL levels were observed with respect to functional class, age at disease onset, disease duration and/or other clinical parameters such as nodules, secondary Sjögren syndrome, anti-CCP and rheumatoid factor. Differential distribution of serum MBL levels with functional MBL2 variants was observed in respective RA patients and their relatives.

Conclusions

Our results suggest MBL levels as a possible marker for RA susceptibility in a Brazilian population.     

Control of Oxidative Damage in Rheumatoid Arthritis By Gold(I)-Thiolate Drugs

The roles of anti-arthritic gold(I)-thiolate drugs such as disodium aurothiomalate ('Myocrisin') in the modulation or promotion of oxygen radical-mediated oxidative damage in vivo ate reviewed. In particular, the precise molecular mechanisms by which these novel second-line agents exert their therapeutic effects are discussed in terms of (i) the direct and indirect control of enzymes involved in the generation or scavenging of reactive oxygen speices (ROS) such as superoxide ion, hydrogen peroxide and hydroxyl radical, (ii) the protection of proteins and relevant enzyme systems against attack by ROS and (iii) their direct involvement in the production (at appropriate 'target' sites) or scavenging of ROS in vivo. In addition, the role of the orally-effective gold(I)-phosphine complex auranofin in the control of oxidative damage in rheumatoid arthritis is also discussed.