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1.
Yufeng Yin Di Liang Lidan Zhao Yang Li Wei Liu Yan Ren Yongzhe Li Xiaofeng Zeng Fengchun Zhang Fulin Tang Guangliang Shan Xuan Zhang 《PloS one》2014,9(4)
Objective
Patients with rheumatoid arthritis (RA) are at risk to develop RA-associated interstitial lung disease (RA-ILD). This retrospective study aimed to investigate the potential association of the positivity of serum anti-cyclic citrullinated peptide antibody (anti-CCP2) and rheumatoid factor (RF) with RA-ILD in RA patients.Methods
A total of 285 RA patients were recruited at the inpatient service of Peking Union Medical College Hospital in China between 2004 and 2013. Individual patients were evaluated for the evidence of ILD. The concentrations of serum anti-CCP2 and RF in individual patients were measured. The potential risk factors for ILD in RA patients were assessed by univariate and multivariate models.Results
There were 71 RA patients with RA-ILD, accounting for 24.9% in this population. The positive rates of anti-CCP2 and RF in the patients with RA-ILD were significantly higher than that in the patients with RA-only (88.7% vs. 67.3%, p<0.001; 84.5% vs. 70.6%, p = 0.02, respectively). Univariate and multivariate logistic regression analysis revealed that RA patients with positive serum anti-CCP2, but not RF, were associated with an increased risk of ILD (crude odds ratio [cOR] 3.83, 95% confidence interval [CI] 1.74–8.43, p<0.001; adjusted odds ratio [aOR] 3.50, 95% CI 1.52–8.04, p<0.001).Conclusion
Our findings suggest that positive serum anti-CCP2, but not RF, may be associated with RA-ILD in RA patients. 相似文献2.
Citrullination, a posttranslational modification of peptidyl arginine to citrulline, plays an essential role in rheumatoid arthritis (RA). Citrullination is catalyzed by a group of peptidylarginine deiminases (PADs) including PADI 1, 2, 3, 4 and 6. Many studies have indicated that the gene encoding PADI4 is a factor in susceptibility to RA. Some studies have detected PADI2 expression in RA synovial tissues, suggesting that PADI2 also plays an important role in the disease. This study evaluated the possible association between the PADI2-encoding gene and RA. Seventeen tag SNPs across the PAD locus were genotyped using a custom-designed Illumina 96-SNP VeraCode microarray. Peripheral blood samples were collected from patients with RA (n = 267), ankylosing spondylitis (AS, n = 51) and healthy controls (n = 160). The results of genotyping were verified using Sequenom MassARRAY in an independent cohort of 307 patients with RA, 324 patients with AS and 509 healthy controls. A western blot analysis was performed using synovial tissue from patients with RA (n = 7), osteoarthritis (OA, n = 7) and AS (n = 5) to determine the levels of expression of PADI2. A microarray analysis revealed a significant association between three selected PADI2 SNPs (rs2235926, rs2057094, rs2076616) and the presence of RA. The increased susceptibility to RA associated with rs2235926 (OR = 1.706733, 95% CI = [1.576366–1.866587], p = 0.000839) and rs2057094 (OR = 1.360432, 95% CI = [1.065483–1.869482], p = 0.003291) was further confirmed by the Sequenom MassARRAY. No tag SNPs in the PADI2 locus showed a significant association with AS. Increased expression of PADI2 was detected in RA synovial tissues compared with samples from patients with OA and AS. PADI2 is significantly associated with RA and may be involved in the pathogenesis of the disease. 相似文献
3.
目的:探讨血清抗角蛋白抗体谱对类风湿关节炎预后的判断价值。方法:选择早期、活动性类风湿关节炎患者82例(病程≤6个月),分为病例组(抗角蛋白抗体谱阳性组,n=39)和对照组(抗角蛋白抗体谱阴性组,n=43),均给予相同的治疗方案,在治疗前、治疗后12个月、治疗后24个月分别记录全部患者的关节肿胀数、关节压痛数、晨僵时间和红细胞沉降率的变化,通过治疗前及治疗后24个月分别记录手足X线正位片、Sharp评分和DAS28评分标准进行评价。结果:治疗12个月后病例组临床指标的改善较对照组差(P〈0.01);24个月后病例组X线分期变化情况进展明显大于对照组(P〈0.01)。结论:抗角蛋白抗体阳性谱患者的临床指标和影像学变化情况较抗角蛋白抗体谱阴性患者对治疗的反应较差,更易发生关节破坏。 相似文献
4.
Na Yu Fang Han Xiaojun Lin Chun Tang Jinghua Ye Xiaoyan Cai 《Biological trace element research》2016,169(1):46-51
5.
Association of SLC22A4 Gene Polymorphism with Rheumatoid Arthritis in the Chinese Population
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Tian‐li Ren Zhi‐jun Han Cheng‐jian Yang Yuan‐xing Hang De‐yu Fang Ke Wang Xue Zhu Xiao‐jing Ji Fan‐fan Zhou 《Journal of biochemical and molecular toxicology》2014,28(5):206-210
Rheumatoid arthritis (RA) is a chronic inflammatory disease with complex genetic factors. Single‐nucleotide polymorphisms (SNPs) in the SLC22A4 gene have been previously reported to be associated with RA in Japanese but not European populations. This study further investigated the association of SLC22A4 polymorphisms, in particular slc2F1/slc2F2, with RA in the Chinese population, the largest Asian population. A total of 160 human subjects with 95 RA patients and 65 healthy controls were genotyped for slc2F1‐G/A and slc2F2‐C/T polymorphisms. The results showed that there was a significant difference in the genotype distribution of these two polymorphisms between the two groups. In addition, the presence of slc2F1 A allele and slc2F2 T allele carries a 1.93‐fold and 2.14‐fold increased risk for anticyclic citrullinated peptide (CCP) positivity, respectively. Overall, this study provided evidence that SLC22A4 gene polymorphisms played important roles in the etiology of RA in the largest Asian population, the Chinese population. 相似文献
6.
Gao-yun Yang Xue Chen Ya-chun Sun Chen-li Ma Ge Qian 《International journal of biological sciences》2013,9(8):759-765
Background: Human chemokine-like factor 1 (CKLF1), a recently discovered chemokine, has a broad spectrum of biological functions in immune-mediated diseases. It is highly expressed on Th2 lymphocytes and is a functional ligand for human CCR4. CKLF1 has a major role in the recruitment and activation of leucocytes, which plays an important role in the pathogenesis of allergic diseases. The present study was designed to determine the expression of CKLF1 in skin and serum in patients with atopic dermatitis (AD).Methods: The CKLF1 protein expression in skin lesion was analyzed by immunohistochemistry and ELISA. The mRNA expression of CKLF1 in skin lesion was detected by Real-time PCR. The serum levels of CKLF1, IgE, eotaxin, IL-4, IL-5, and IL-13 were measured by ELISA.Results: Histopathological changes in the skin of AD patients showed local inflammation with epidermal thickening and significant inflammatory cellular infiltration. Immunohistochemistry results demonstrated that CKLF1-staining positive cells were located in the epidermal and dermis, and that the CKLF1 expression in AD patients was significantly higher than that in normal control. The CKLF1 mRNA expression in AD patients was significantly higher than that in healthy controls. Serum CKLF1 and IgE levels were significantly increased in AD patients, as were the serum levels of IL-4, IL-5, IL-13 and eotaxin.Conclusions: Both CKLF1 protien and mRNA levels are overexpressed in the skin lesion of AD patients, along with an increase in serum CKLF1 level, indicating that CKLF1 may play an important role in the development of atopic dermatitis. 相似文献
7.
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. 相似文献
8.
Kresten Krarup Keller Jesper Skovhus Thomsen Kristian Stengaard-Pedersen Frederik Dagn?s-Hansen Jens Randel Nyengaard Ellen-Margrethe Hauge 《PloS one》2012,7(12)
Introduction
Arthritic bone loss in the joints of patients with rheumatoid arthritis is the result of a combination of osteoclastic bone resorption and osteoblastic bone formation. This process is not completely understood, and especially the importance of local inflammation needs further investigation. We evaluated how bone formation and bone resorption are altered in experimental autoimmune arthritis.Methods
Twenty-one female SKG mice were randomized to either an arthritis group or a control group. Tetracycline was used to identify mineralizing surfaces. After six weeks the right hind paws were embedded undecalcified in methylmethacrylate. The paws were cut exhaustively according to the principles of vertical sectioning and systematic sampling. 3D design-based methods were used to estimate the total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast-covered bone surfaces. In addition the presence of adjacent inflammation was ascertained.Results
The total number of osteoclasts, mineralizing surfaces, eroded surfaces, and osteoclast covered surfaces were elevated in arthritic paws compared to normal paws. Mineralizing surfaces were elevated adjacent to as well as not adjacent to inflammation in arthritic mice compared to normal mice. In arthritic mice, eroded surfaces and osteoclast covered surfaces were larger on bone surfaces adjacent to inflammation than on bone surfaces without adjacent inflammation. However, we found no difference between mineralizing surfaces at bone surfaces with or without inflammation in arthritic mice.Conclusions
Inflammation induced an increase in resorptive bone surfaces as well as formative bone surfaces. The bone formative response may be more general, since formative bone surfaces were also increased when not associated with inflammation. Thus, the bone loss may be the result of a substantial local bone resorption, which cannot be compensated by the increased local bone formation. These findings may be valuable for the development of new osteoblast targeting drugs in RA. 相似文献9.
10.
目的:检测类风湿性关节炎患者血清EBV(Epstein-Barr virus)衣壳抗原IgA抗体(VCA-IgA),分析EBV感染与类风湿性关节炎的相关性.方法:用酶联免疫吸附试验(ELISA)检测92例确诊为类风湿性关节炎患者和80例体检健康者血清VCA-IgA抗体,分析两组人群EBV VCA-IgA阳性率.结果:类风湿性关节炎患者VCA-IgA抗体阳性率为9.8%(9/92);健康对照组阳性率为2.4% (2/85)(x2=4.038,P<0.05).结论:类风湿性关节炎患者血清EBV VCA-IgA抗体检出率明显高于健康对照组,提示部分类风湿性关节炎患者发病与EBV感染有关. 相似文献
11.
目的:分析应用英夫利昔单抗(INF)治疗的类风湿关节炎(RA)患者的临床和实验等指标,筛选出可预测INF疗效的因素.方法:以应用INF治疗的40例RA患者为研究对象,收集基线和第14用的临床和实验等指标.应用聚合酶链反应一限制性片断长度分析法(PCR-RFLP)检测RA患者的肿瘤坏死因子α-308(TNFα-308)A/G的基因多态性.达到ACR50%-70%改善的的被判断为INF治疗反应好.采用Logistic回归模型筛选出可预测疗效的因素.结果:治疗14周后.携带TNF-308G/G基因型的RA患者,达到ACR20、ACR50、ACR70改善标准的患者人数的百分率分别为93%、64%和30%;A/G基因型,ACR20、ACR50、ACR70的百分率分别为60%、40%和20%.多因素Logistic回归分析显示,基线值中高DAS28评分和携带TNF-308G/G基因型的RA患者,对INF治疗反应好,其OR值分别为1.97(95%CI为1.74-3.13,P<0.01)和2.02(95%CI为1.93-3.91,P<0.01).结论:高DAS28评分及携带TNF-308 G/G基因型的RA患者对INF治疗有更好的应答.RA患者的DAS28评分及携带TNF-308 G基因型可能可作为INF治疗RA疗效的预测指标. 相似文献
12.
Michael V. Holmes Benyu Jiang Karen McNeill Melinda Wong Stephen P. Oakley Bruce Kirkham Phil J. Chowienczyk 《PloS one》2010,5(4)
Background
Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA).Methodology/Principal Findings
Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P<0.01).Conclusions/Significance
These findings argue against a causal role of CRP in atherogenesis and are consistent with a protective effect of CRP on EDNO bioavailability. 相似文献13.
《Gender Medicine》2012,9(6):490-510.e5
BackgroundData on the effect of gender in rheumatoid arthritis (RA) in non-Caucasian populations is scarce. Latin America and the Caribbean (LAC) is a large population with unique characteristics, including high admixture.ObjectiveOur aim was to examine the effect of gender in patients with RA in LAC.MethodsThis was a 2-phase study. First we conducted a cross-sectional and analytical study in which 1128 consecutive Colombian patients with RA were assessed. Second, a systematic review of the literature was done to evaluate the effect of gender in LAC patients with RA.ResultsOur results show a high prevalence of RA in LAC women with a ratio of 5.2 women per man. Colombian women with RA are more at risk of having an early age at onset and developing polyautoimmunity and abdominal obesity, and they perform more household duties than their male counterparts. However, male gender was associated with the presence of extra-articular manifestations. Of a total of 641 potentially relevant articles, 38 were considered for final analysis, in which several factors and outcomes related to gender were identified.ConclusionsRA in LAC women is not only more common but presents with some clinical characteristics that differ from RA presentation in men. Some of those characteristics could explain the high rates of disability and worse prognosis observed in women with RA in LAC. 相似文献
14.
15.
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. 相似文献
16.
Sho Mokuda Yosuke Murata Naoya Sawada Kenichiro Matoba Akihiro Yamada Makoto Onishi Yasuaki Okuda Kazuo Jouyama Eiji Sugiyama Kiyoshi Takasugi 《PloS one》2013,8(8)
Factor XIII is one of the twelve coagulation factors and also known as a fibrin-stabilizing factor. In 2012, we encountered a male RA patient with hemorrhagic factor XIII deficiency who had been treated with tocilizumab for two years. There are few reports regarding the relationship between tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)) and factor XIII. We measured the factor XIII activity levels in the plasma of 40 RA patients (10 patients treated without biologics, 30 patients treated with biologics (15 patients treated with necrosis factor inhibitors and 15 patients treated with tocilizumab)) and 19 healthy controls. Consequently, the tocilizumab group exhibited lower levels than the other three groups according to the Steel-Dwass test (P<0.01). Furthermore, we compared the plasma factor XIII activity levels and the plasma factor XIII concentrations in the RA patients treated with biologics. Pearson''s correlation test was used to assess the relationship between the factor XIII activity levels and the plasma factor XIII concentrations (r = 0.449, P = 0.019). According to the multiple regression analysis, the treatment with tocilizumab is an independent risk factor for plasma factor XIII reduction in RA patients. In conclusion, RA patients treated with tocilizumab, an IL-6R blocker, are at risk of developing acquired factor XIII deficiency. The mechanisms underlying the reduced factor XIII activity observed in RA patients treated with tocilizumab may result from the quantitative reduction in the plasma. These data imply that IL-6 plays an important role in maintaining the factor XIII activity level. 相似文献
17.
Rheumatoid arthritis (RA) is a chronic, systematic autoimmune disease that mainly affects joints and bones. Although the precise etiology is still unknown, Th17 cell is being recognized as an important mediator in pathogenesis of RA. VSTM1-v2 is a novel cytokine which has recently been reported to promote the differentiation of Th17 cells. This study is performed to study whether VSTM1-v2 can be recognized as a biomarker of RA, and is correlated to IL-17 expression. We obtained peripheral blood mononuclear cells (PBMCs) from 40 patients with RA and 40 age- and sex- matched healthy controls by standard Ficoll-Paque Plus density centrifugation. The mRNA expression levels of VSTM1-v2 and IL-17A in PBMCs were detected by real time-PCR. Disease activity parameters of RA were measured by routine methods. Our results showed that VSTM1-v2 mRNA expression in PBMCs from RA patients was significantly increased in comparison of that in healthy individuals. The VSTM1-v2 mRNA expression level was positively correlated with IL-17A mRNA expression level, DAS28, CRP and ESR, but was not correlated to RF, Anti-CCP or ANA. VSTM1-v2 might be a biomarker of RA and a novel factor in the pathogenesis of RA. 相似文献
18.
Vesa-Petteri Kouri Juri Olkkonen Emilia Kaivosoja Mari Ainola Juuso Juhila Iiris Hovatta Yrj? T. Konttinen Jami Mandelin 《PloS one》2013,8(1)
Introduction
Patients with rheumatoid arthritis (RA) have disturbances in the hypothalamic-pituitary-adrenal (HPA) axis. These are reflected in altered circadian rhythm of circulating serum cortisol, melatonin and IL-6 levels and in chronic fatigue. We hypothesized that the molecular machinery responsible for the circadian timekeeping is perturbed in RA. The aim of this study was to investigate the expression of circadian clock in RA.Methods
Gene expression of thirteen clock genes was analyzed in the synovial membrane of RA and control osteoarthritis (OA) patients. BMAL1 protein was detected using immunohistochemistry. Cell autonomous clock oscillation was started in RA and OA synovial fibroblasts using serum shock. The effect of pro-inflammatory stimulus on clock gene expression in synovial fibroblasts was studied using IL-6 and TNF-α.Results
Gene expression analysis disclosed disconcerted circadian timekeeping and immunohistochemistry revealed strong cytoplasmic localization of BMAL1 in RA patients. Perturbed circadian timekeeping is at least in part inflammation independent and cell autonomous, because RA synovial fibroblasts display altered circadian expression of several clock components, and perturbed circadian production of IL-6 and IL-1β after clock resetting. However, inflammatory stimulus disturbs the rhythm in cultured fibroblasts. Throughout the experiments ARNTL2 and NPAS2 appeared to be the most affected clock genes in human immune-inflammatory conditions.Conclusion
We conclude that the molecular machinery controlling the circadian rhythm is disturbed in RA patients. 相似文献19.