Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis

We attempted to determine whether various cytokine levels in the serum and synovial fluid (SF) of rheumatoid arthritis (RA) patients are influenced by the performance of filtration leukocytapheresis (LCP). The filtration LCP procedure that used a Cellsorba® column (LCP group: n=22; responder subgroup: n=17, non‐responder subgroup: n=5) or sham apheresis (control group; n=7) was repeated three times at 1‐week intervals. Serum (LCP group, n=22; control group, n=7) and SF (LCP group, n=6; control group, n=3) samples were collected before and after LCP. Levels of tumor necrosis factor α (TNFα), interleukins (IL‐1β, IL–2, IL‐6, IL‐8, IL‐10, and IL‐15), granulocyte–macrophage colony–stimulating factor (GM‐CSF), monocyte chemoattractant protein–1 (MCP‐1), RANTES were measured by an enzyme‐linked immunosorbent assay. Serum TNFα, IL‐15, and RANTES were significantly reduced only in the LCP group. Serum IL‐10 significantly increased only in the LCP group. In the LCP subgroup, serum IL‐15, GM‐CSF, and RANTES levels were reduced significantly, while serum IL‐10 levels increased significantly only in the responder group after treatment. Serum TNFα levels were reduced significantly in both subgroups. Changes in serum IL‐10 correlated positively with the improvement of patient's assessment of pain and global severity, and physician's assessment of global severity. These results indicate that the removal of leukocytes from the peripheral blood of RA patients provokes dynamic changes in some cytokine levels in the serum and/or synovial fluid. These changes may explain some of the mechanisms by which the articular symptoms are improved by filtration LCP. J. Clin. Apheresis. 16:74–81, 2001. © 2001 Wiley‐Liss, Inc.     

Edaravone inhibits the disease activity in rheumatoid arthritis

A male patient with rheumatoid arthritis (RA) developed acute stroke and was treated with the free radical scavenger, edaravone. Polyarthralgia improved with a reduction in serum C-reactive protein concentration soon after the start of edaravone administration. The disease activity score 28 (DAS28) also decreased. Edaravone appears to be effective for the control of RA. The usefulness of this potentially novel therapeutic agent should be tested in a well designed randomized controlled trial.     

Self-determination of patients with rheumatoid arthritis: model development during action research

The purpose of this article is to describe the content and the development of the model to promote self-determination of patients with rheumatoid arthritis from a point of view of patients and nurses. For the patients the data were gathered using semistructured interviews and for the nurses through three focus groups in the initial and evaluation phases. The data were analysed by themes using qualitative content analysis. The model consisted of the concept of self-determination, impediments to and preconditions for self-determination, promoting and focusing on consequences. Patient's activity was a new view of the concept. Impediments to self-determination were linked to limitations and preconditions to patients' freedom to express themselves. Support developed an important factor promoting self-determination. The results indicate a clear need for various types of supportive nursing care to promote self-participation in patient care.     

类风湿关节炎患者天然、氧化脂蛋白(a)水平

目的分析类风湿关节炎(RA)患者天然、氧化脂蛋白(a)[Lp(a)]水平及其与炎症的关系,探讨Lp(a)在RA患者心血管病发生中的意义。方法选择RA患者56例,其中活动性24例,非活动性32例;正常对照60例。对受检者天然、氧化Lp(a)水平以及炎症指标进行检测。结果活动性RA患者天然、氧化Lp(a)水平均高于非活动性RA患者和对照组,而非活动组和对照组间无变化。血沉和C反应蛋白均分别与天然、氧化Lp(a)呈正相关。结论RA患者天然、氧化Lp(a)水平发生显著变化,炎症反应对Lp(a)代谢具调节作用,参与动脉粥样硬化的发生、发展。     

Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice

Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation, host defense, and the neuro-immuno-endocrine network. IL-1 receptor antagonist (ra) is an endogenous inhibitor of IL-1 and is supposed to regulate IL-1 activity. However, its pathophysiological roles in a body remain largely unknown. To elucidate the roles of IL-1ra, IL-1ra-deficient mice were produced by gene targeting, and pathology was analyzed on different genetic backgrounds. We found that all of the mice on a BALB/cA background, but not those on a C57BL/6J background, spontaneously developed chronic inflammatory polyarthropathy. Histopathology showed marked synovial and periarticular inflammation, with articular erosion caused by invasion of granulation tissues closely resembling that of rheumatoid arthritis in humans. Moreover, elevated levels of antibodies against immunoglobulins, type II collagen, and double-stranded DNA were detected in these mice, suggesting development of autoimmunity. Proinflammatory cytokines such as IL-1beta, IL-6, and tumor necrosis factor alpha were overexpressed in the joints, indicating regulatory roles of IL-1ra in the cytokine network. We thus show that IL-1ra gene deficiency causes autoimmunity and joint-specific inflammation and suggest that IL-1ra is important in maintaining homeostasis of the immune system. Possible involvement of IL-1ra gene deficiency in RA will be discussed.     

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a Th1/Th17‐mediated autoimmune disease whose current treatment, consisting in the blockage of inflammatory cytokines by disease‐modifying antirheumatic drugs, is not effective for all patients. The therapeutic potential of mesenchymal stromal/stem cells' (MSCs) immunomodulatory properties is being explored in RA. Here, we investigate the effect of human bone marrow (BM)‐MSCs on the expression of cytokines involved in RA physiopathology by the distinct functional compartments of CD4⁺ and CD8⁺ T cells from RA patients. Peripheral blood mononuclear cells from healthy individuals (n = 6) and RA patients (n = 12) were stimulated with phorbol myristate acetate plus ionomycin and cultured in the presence/absence of BM‐MSCs. The expression of (interleukin) IL‐2, tumor necrosis factor alpha (TNF‐α), and interferon‐gamma (IFN‐γ) was evaluated in naive, central memory, effector memory, and effector CD4⁺ and CD8⁺ T cells, whereas IL‐6, IL‐9, and IL‐17 expression was measured in total CD4⁺ and CD8⁺ T cells. mRNA expression of IL‐4, IL‐10, transforming growth factor beta (TGF‐β), cytotoxic T‐lymphocyte‐associated antigen 4, and/or forkhead box P3 was quantified in fluorescence‐activated cell sorting‐purified CD4⁺ T cells, CD8⁺ T cells, and CD4⁺ Treg. BM‐MSCs inhibited the production of TNF‐α, IL‐17, IL‐6, IL‐2, IFN‐γ, and IL‐9 by T cells from RA patients, mainly by reducing the percentage of cells producing cytokines. This inhibitory effect was transversal to all T cell subsets analyzed. At mRNA level, BM‐MSCs increased expression of IL‐10 and TGF‐β by CD4⁺ and CD8⁺ T cells. BM‐MSCs displayed a striking inhibitory action over T cells from RA patients, reducing the expression of cytokines involved in RA physiopathology. Remarkably, BM‐MSC‐derived immunomodulation affected either naive, effector, and memory T cells.     

蜂针疗法治疗类风湿性关节炎的疗效观察

目的观察蜂针疗法对类风湿关节炎患者的临床疗效。方法将75例符合类风湿性关节炎诊断标准的患者随机分为蜂针组、药物组和蜂针+药物组。比较3组的疗效。结果治疗结束后以及治疗结束后3个月随访,3组患者关节疼痛度、关节肿胀度、关节压痛度、晨僵时间(h)、关节疼痛数变化、HAQ、ESR、RF、CRP均有显著差异(P0.05)。结论蜂针疗法能有效缓解类风湿关节炎患者的临床症状。     

Calprotectin levels in rheumatoid arthritis and their correlation with disease activity: a meta-analysis

Objective: We evaluated the relationship between calprotectin levels and rheumatoid arthritis (RA), and the correlation between plasma/serum calprotectin and RA activity.

Methods: We searched PUBMED, EMBASE, and Cochrane databases and performed meta-analyses comparing plasma/serum or synovial fluid calprotectin levels in RA patients and controls, and correlation coefficients between calprotectin levels and disease activity for 28 joints (DAS28) as well as C-reactive protein (CRP) in RA patients.

Results: Sixteen studies including 849 RA patients and 266 controls were available for meta-analysis. Meta-analysis showed that calprotectin levels were significantly higher in the RA group than in the control group (SMD = 2.337, 95% CI = 1.544–3.130, p < 1.0 × 10^–8). Stratification by rheumatoid factor (RF) status revealed significantly elevated calprotectin levels in the RF-positive RA group compared to that of the RF-negative RA group (SMD = 0.574, 95% CI = 0.345–0.804, p = 9.2 × 10^–7). Meta-analysis of correlation coefficients identified a significant positive correlation between calprotectin levels and CRP or DAS28 (correlation coefficient for CRP = 0.566, 95% CI = 0.512–0.615, p < 1.0 × 10^–8; correlation coefficient for DAS28 = 0.438, 95% CI = 0.269–0.518, p = 2.5 × 10^–6). Calprotectin levels in synovial fluid were significantly higher in the RA group than in the control group (SMD = 2.891, 95% CI = 1.067–4.715, p = 0.002).

Conclusions: Our meta-analysis demonstrates that circulating and synovial fluid calprotectin levels are high in patients with RA, and that circulating calprotectin levels positively correlate with RA activity.     

抗氧化能力在类风湿性关节炎患者中的临床意义及与疾病活动的关系

目的探讨抗氧化能力在类风湿性关节炎(RA)发病机制及疾病进展中的作用。方法选取RA患者91例作为病例组,根据RA疾病活动性评分(DAS 28)将病例组分为低活动组和中高活动组,健康体检者70例作为健康对照组,并记录相关临床及实验室指标。检测血清总抗氧化状态(TAS)和超氧化物歧化酶(SOD)水平,并分析其与RA各项临床及实验室指标的相关性。应用SPSS 17.0进行统计学分析。结果 RA组中高活动组TAS、SOD水平显著低于低活动组及健康对照组,低活动组TAS、SOD水平显著低于健康对照组,差异有统计学意义(P0.05)。RA患者血清TAS、SOD水平与类风湿因子(RF)、压痛关节数(TJC)、肿胀关节数(SJC)、C-反应蛋白(CRP)、红细胞沉降率(ESR)、DAS 28呈负相关(P0.05)。结论氧化应激参与RA的致病过程,血清抗氧化标志物SOD和TAS水平与疾病活动性相关可用于RA辅助诊断和疗效观察。     

High HDL-cholesterol in women with rheumatoid arthritis on low-dose glucocorticoid therapy

Background Dyslipidaemia has been described in non‐treated rheumatoid arthritis (RA), and improves after therapy with disease modifying anti‐rheumatic drugs or glucocorticoids; however, it has generally been perceived that glucocorticoids adversely affect lipid metabolism. The association of low dose glucocorticoid therapy with plasma lipid levels was evaluated in female RA patients. Materials and methods A cross‐sectional study was conducted in 78 female RA patients [mean age: 60 (12) years; mean disease duration: 13 (9) years]. Sixty‐five (83%) were on glucocorticoid therapy [total equivalent mean prednisone dose: 5·1 (1·7) mg d^?1]. Each patient was assessed through a self‐reported questionnaire, structured interview and physical examination. Blood samples were obtained for routine biochemistry, lipid profile and haematological tests. Lipid profiles of RA patients who were and were not on glucocorticoid therapy were compared. Results Clinical and laboratory features of the two groups of patients were similar, except for the Health Assessment Questionnaire and body mass index, which were significantly higher in the patients on glucocorticoid therapy. These patients had 14·7% higher serum high‐density lipoprotein cholesterol (HDL‐c) levels than untreated patients (P = 0·043), mainly at the expense of HDL2 subfraction, which was 24·4% higher (P < 0·039), whereas HDL3‐c was only 7·4% higher (P = 0·219). Serum levels of glucose and total cholesterol, triglyceride, low‐density lipoprotein cholesterol (LDL ‐c), very low‐density lipoprotein cholesterol, apolipoproteins A‐I and B were not increased in patients on glucocorticoid therapy. Conclusions Low dose glucocorticoid therapy in RA patients is associated with an increase in HDL‐c, without increasing LDL‐c or triglyceride. These lipid changes may overall be considered favourable.     

抗环瓜氨酸肽抗体联合类风湿因子诊断类风湿关节炎的临床意义

目的探讨类风湿关节炎(RA)血清标志物抗环瓜氨酸肽(CCP)抗体的临床价值,并分析其与类风湿因子(RF)的关联性。方法采用化学发光法检测CCP抗体,使用免疫散射比浊法检测RF,并对结果进行统计学分析。结果 113例RA患者抗CCP抗体对RA诊断的敏感性73.5%,阳性83例;84例非RA患者抗CCP抗体特异性97.6%,阳性2例。82例抗CCP抗体与RF检测结果相同(72.6%)。两者无相关性(P0.05)。抗CCP抗体与RF联合检测的敏感性84.1%,特异性98.8%。结论抗CCP抗体与RF抗体联合检测可提高RA的特异性。     

The effects of knee extensor and flexor muscle training on the timed-up-and-go test in individuals with rheumatoid arthritis

Background and Purpose. Rheumatoid arthritis frequently results in functional impairment. This study investigated the effect of a specific exercise regimen on function. Method. A randomized controlled assessor-blinded (N = 36) compared the effect of knee extensor and f lexor muscle training on pain, the timed up and go (TUG) test and the Health Assessment Questionnaire in subjects with non-acute rheumatoid arthritis. Results. Knee extensor and flexor muscle training increased isokinetic torques at speeds of 60°/sec^?1 and 120°/sec^?1 as measured by an isokinetic dynamometer (p = 0.02–0.003). The experimental group experienced a reduction in pain (p = 0.03), an improvement in TUG time (p = 0.01) and in function as measured by the Health Assessment Questionnaire (p = 0.04). Conclusions. Specific knee muscle training can be administered safely in people with non-acute rheumatoid arthritis, and may produce functional benefits.     

类风湿性关节炎患者36例护理指导

目的：研究类风湿性关节炎护理指导对疾病康复的作用。方法：给患者讲解RA基本知识,使其正确掌握服药方法,对活动期患者给予生活护理,稳定期帮助督促关节功能锻炼。结果：护理指导12周、24周时总有效率分别是80．7％和86．1％,临床和实验室指标都有不同程度的改善,关节功能分级护理指导前Ⅱ～Ⅳ级占88．9％,24周时降至55．6％,有显著性差异（P＜0．01）。期间未发生严重不良反应。结论：RA患者的护理指导能有效改善病情,降低致残率。     

14847例就诊患者类风湿关节炎相关自身抗体检测结果分析

目的：探讨就诊人群中抗环瓜氨酸肽（CCP）抗体、抗角蛋白抗体（AKA）、抗 RA33抗体、磷酸6葡萄糖异构酶（GPI）、类风湿因子（RF）等类风湿关节炎相关抗体的阳性分布趋势,及其在不同疾病中的分布与临床应用价值。方法用固相酶联免疫吸附法（ELISA）检测抗 CCP 抗体、抗 RA33抗体、磷酸6葡萄糖异构酶（GPI）、用间接免疫荧光法检测 AKA,用免疫比浊法检测 RF。结合患者临床资料分析这些自身抗体在不同年龄、性别和疾病中的阳性分布趋势及临床应用价值。结果抗 CCP 抗体、AKA、抗 RA33抗体、GPI、RF 例就诊人群的阳性率分别为26．22％、6．65％、7．13％、41．19％、32．95％;女性中抗 RA33抗体阳性率高于男性,男性抗 CCP 抗体阳性率高于女性（P ＜0．05）。在 RA 患者组各种抗体阳性率明显高于其他组,且抗体滴度也明显高于其他组。结论抗 CCP 抗体、AKA、抗 RA33抗体、GPI、RF 主要见于类风湿关节炎患者,但是也可出现在其他疾病中,但滴度较低。因此在临床诊疗过程需综合分析,应避免片面根据自身抗体检查结果所致误诊。     

类风湿关节炎单独甲氨蝶呤与三联疗法治疗的系统评价

背景：目前类风湿关节炎在治疗上选择甲氨蝶呤单独疗法还是三联疗法存在争议。目的：系统评价甲氨蝶呤单独疗法与甲氨喋呤＋羟氯喹＋柳氮磺吡啶三联疗法比较治疗类风湿关节炎的有效性和安全性。方法：计算机检索 Cochrane 图书馆、PubMed、EMBASE NRR （http：//www.updatesoftware.com/National）、CCT（http：//www.control ed-trails.com）和中国生物医学文献数据库（CBM）。手工检索（中文主要骨科杂志）。收集甲氨蝶呤单独疗法与甲氨喋呤＋羟氯喹＋柳氮磺吡啶三联疗法比较治疗类风湿关节炎的随机对照试验,并评价纳入研究的方法学质量。统计采用Cochrane协作网提供的Revman 5.0软件进行分析。结果与结论：共纳入随机对照试验4篇,共297例患者,方法学质量均为B 级。Meta分析结果表明,甲氨蝶呤单独疗法与三联疗法比较,甲氨蝶呤单独疗法在血沉方面的改善要大于三联疗法[MD=7.0195%CI（2.82,11.19）,P=0.001],三联疗法在关节改善情况方面优于单独疗法[OR=0.6295%（0.41,0.95）,P=0.03],在不良反应上,两者差异无显著性意义。而ACR因文献未提供详细数据未能做Meta分析。与三联疗法治疗相比,甲氨蝶呤单独疗法更明显降低成人类风湿关节炎的血沉,但在关节功能改善方面三联疗法要优于甲氨蝶呤单独疗法。而在不良反应上,两组差异无显著性意义。因这次系统评价纳入的病例数较少,尚需更多设计严格的大样本随机对照研究来增加证据的强度。     

类风湿性关节炎患者IL-15、IL-18的水平变化及意义

目的 研究类风湿性关节炎(RA)患者血清IL-15、IL-18的变化及其临床意义.方法 收集30例RA患者,以20例骨关节炎(OA)患者和10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-15、IL-18的水平,并测定类风湿因子和C反应蛋白.结果 RA患者的血清IL-15、IL-18的含量明显高于OA组及健康体检组,RA患者的类风湿因子明显高于对照组,C反应蛋白的含量在各组间差异无统计学意义.结论 IL-15、IL-18在RA患者的疾病发展过程中发挥着重要作用,阻断IL-15、IL-18的生物活性,为靶向治疗RA患者提供了新思路.     

类风湿关节炎患者血清中C反应蛋白、脂联素水平与患者病情严重程度及患者关节功能的关系

目的探讨类风湿关节炎(RA)患者血清中C反应蛋白(CRP)、脂联素(APN)水平与患者病情严重程度及患者关节功能的关系。方法选择2014年9月至2016年8月该院治疗的85例RA患者纳入RA组,同期20例健康体检者为对照组,检测患者血清中CRP、APN,探讨CRP、APN水平与患者RA患者病情及患者关节功能的关系。结果 RA患者CRP为(23.63±5.36)pg/mL明显高于对照组;APN、APN/CRP分别为(4.64±1.74)ng/mL、0.37±0.06,明显低于对照组,差异均有统计学意义(P0.05)。RA患者关节损伤越严重,APN、APN/CRP越低,而CRP水平越高,且组间差异均有统计学意义(P0.05)。病情活动分级越高的患者APN、APN/CRP越低,而CRP水平越高,且差异有统计学意义(P0.05)。Logistic分析结果提示APN(P=0.04)、APN/CRP(P=0.01)是RA患者出现骨损伤的独立危险因素。结论血清中CRP、APN水平与RA患者病情严重程度及患者关节功能密切相关。     

抗环瓜氨酸肽抗体在类风湿关节炎中的应用

目的类风湿关节炎(RA)是一种致畸性较高的自身免疫性疾病,本实验探讨抗环瓜氨酸肽抗体(抗-CCP)和类风湿因子(RF)对RA的诊断作用。方法用酶联免疫吸附试验法测定抗-CCP,用速率散射免疫比浊检测RF。结果 380例RA患者抗-CCP和RF阳性率分别为63.4%、68.2%;152例非RA患者抗-CCP和RF阳性率2.0%、15.1%;抗-CCP和RF对RA诊断的灵敏度分别为63.4%、68.9%,特异性分别为98%、84.9%,二者联合时特异性达到97.4%。结论抗-CCP在RA诊断中有良好的灵敏度和特异性,二者联合能极大地提高RA诊断的准确性。     

Circulating levels of prolactin are elevated in patients with rheumatoid arthritis: a meta-analysis

Background: Prolactin (PRL), an inflammatory hormone with cytokine properties, has long been proposed to play a crucial role in the pathogenesis of autoimmune disorders, including rheumatoid arthritis (RA). However, the circulating levels of PRL in RA were discordant among published studies.

Methods: PubMed, Embase, and The Cochrane Library database were systematically searched from inception up to 30 June 2018. The available studies were obtained from the initial search in accordance with the rigorous inclusion and exclusion criteria. Relevant data from the included literatures were extracted. Methodological quality was evaluated in order to refine the final search results. All statistical analyses were conducted using software STATA version 12.0.

Results: Of 698 articles were yielded for eligibility, a finally analysis involving 628 RA cases and 430 controls from 14 published studies were included. When compared to healthy controls, there was a significantly higher level of circulating PRL in patients with RA with a pooled SMD of 1.08 (95% CI = 0.41 to 1.74, P< 0.001), particularly in Asians, age ≥50, enzyme-linked immunosorbent assay (ELISA) group and subjects with erythrocyte sedimentation rate (ESR) ≥25 mm/h.

Conclusions: Our meta-analysis demonstrates a significantly higher level of circulating PRL in RA patients when compared to healthy controls, and it was associated with region, age, measurement type and ESR.