Association of serum hepatoma‐derived growth factor levels with disease activity in rheumatoid arthritis: A pilot study

BackgroundHepatoma‐derived growth factor (HDGF) is reported to play an important role in tumorigenesis and cancer progression. However, growing evidence indicates its participation in immune system activation. This study analyzed the relationship among serum HDGF levels, disease activity, and laboratory markers in patients with rheumatoid arthritis (RA).MethodsBlood samples from 165 patients with RA, 42 with osteoarthritis (OA), and 28 healthy controls, were used to evaluate the serum HDGF levels. Correlations of serum HDGF levels with age, 28‐joint count disease activity score (DAS28), and laboratory findings were assessed by Pearson correlation and receiver operator characteristic (ROC) curve analyses to obtain HDGF optimal cutoffs according to the disease status. Immunohistochemical staining was performed on the knee synovial tissue samples from patients with RA and OA (n = 10 each) to investigate HDGF joint expression.ResultsSerum HDGF levels were significantly correlated with DAS28 erythrocyte sedimentation rate (r = 0.412, p < 0.001) and C‐reactive protein values (r = 0.376, p < 0.001). The optimal cutoffs of serum HDGF levels from the ROC analysis were 5.79 and 5.14 for the differentiation of active/inactive disease and remission/non‐remission, respectively. The ideal cutoff of serum HDGF levels to differentiate RA and OA was determined as 5.47. Serial serum HDGF level analyses in 21 patients with RA revealed that serum HDGF levels significantly decreased after improvement in disease activity (p = 0.046). HDGF expression was not observed in the synovial tissues of the patients with RA and OA.ConclusionSerum HDGF level could be a potential laboratory biomarker for the severity of RA.     

类风湿关节炎患者血清IL-35的水平及其与疾病活动度的关系

目的探讨类风湿关节炎(RA)患者血清IL-35表达水平与疾病活动度的相关性。方法选取确诊RA患者118例,分为活动期组62例和缓解期组56例。同时选取90例健康人作为对照,ELISA法检测RA患者及对照者血清IL-35水平,实时荧光定量PCR检测外周血单个核细胞(PBMC)中IL-35亚基EBI3和P35 mRNA表达水平。分析血清IL-35水平与DAS28评分、C反应蛋白(CRP)、红细胞沉降率(ESR)、类风湿因子(RF)、关节肿胀数(SJC)和关节压痛数(TJC)等的相关性。结果活动期组RA患者血清中IL-35浓度(38.09±16.90)pg/m L显著低于对照组[(82.25±15.82)pg/m L,P0.01)]和缓解期组[(72.96±11.74)pg/m L,P0.01)];依据DAS28评分将活动期组RA患者分为轻度、中度和重度组,血清IL-35水平(pg/m L)在3组中依次降低(轻度60.95±7.31,中度39.68±9.51,重度28.02±9.16),轻度组与中度或重度组间差异具有统计学意义(P0.05)。活动期组和缓解期组患者血清IL-35水平与SJC、CRP和DAS28评分呈负相关性(P0.05),与ESR、TJC、RF无相关性。PBMC中P35 mRNA在RA活动期组中显著降低,低于健康对照组和缓解期组(0.47±0.18 vs 1.91±1.121.82±0.53,P0.01),但EBI3 mRNA在活动期组(1.62±0.68)、缓解期组(1.48±0.77)及对照组(1.86±1.21)中差异无统计学意义(P0.05)。结论活动期组RA患者血清IL-35水平显著下降,且伴随P35 mRNA水平下降,并与RA疾病活动度密切相关,可作为RA疾病活动度评价的潜在指标。     

类风湿关节炎患者血脂水平分析

目的分析类风湿关节炎（RA）患者血脂水平，探讨RA患者心血管疾病的危险性增高与血脂的相关性。方法以RA患者142例（活动组93例、非活动组49例）作为研究对象，86例健康体检者为正常对照，收集晨起空腹静脉血，采用酶法测定血清中甘油三酯（TG）、总胆固醇（TC）和高密度脂蛋白胆固醇（HDL—C）浓度，低密度脂蛋白胆固醇（LDL-C）浓度通过公式进行计算。类风湿因子（RF）和C-反应蛋白（CRP）采用浊度分析法测定。结果与健康对照组比较，RA活动组血清中TC、HDLC、LDL-C水平和RA非活动组TC、HDL—C水平均显著降低（P〈0．001，P〈0．05）；RA活动组与RA非活动组比较，所有指标差异均不具有统计学意义（P〉0．05）。结论RA患者心血管疾病的危险性增高不能完全为血浆TG、TC、HDL-C和LDL-C水平的增减等传统因素所解释，还可能与炎症和血脂在质上的改变等因素有关。     

Relationship between serum ferritin,iron stores and disease activity in rheumatoid arthritis

Summary Bone marrow aspirate from the sternum of 40 patients with active or inactive rheumatoid arthritis (RA) was stained with Perls’ Prussian blue for iron determination. In these patients serum ferritin concentrations were correlated with other indices of iron stores and disease activity. In patients with active RA and without bone marrow iron stores, serum ferritin was significantly lower than in patients with either active or inactive RA and iron stores. In patients with bone marrow iron stores, serum ferritin was directly correlated with erythrocyte sedimentation rate (ESR), Ritchie index, α₁-antitrypsin, α₁-acid glycoprotein and desferrioxamine (DFO)-induced sideruria, while an inverse correlation of serum ferritin with hemoglobin and serum iron was observed. In all patients serum ferritin was significantly correlated only with DFO-induced sideruria and unsaturated iron-binding capacity (UIBC). Thus, serum ferritin is an index of iron stores also in rheumatoid arthritis. In active disease, higher than expected values of serum ferritin are probably due to a shifting of iron from the circulating pool to the reticuloendothelial cells of the synovial membrane.     

类风湿因子与类风湿关节炎疾病活动性及症状程度的相关性(英文)

背景:评价类风湿关节炎患者病情活动性和症状程度传统上一直使用类风湿因子参数,但在目前的临床实践中常出现类风湿因子的数值变化与患者临床改善情况不相符.目的:探讨类风湿因子与类风湿关节炎疾病的活动性及严重程度的相关性.设计、时间及地点:随机横断面调查,于2006-09/2007-09在中山大学附属第三医院风湿免疫科完成.参试者:选择76例类风湿关节炎患者,男11例,女65例,平均年龄(44±13)岁,均符合活动期类风湿关节炎的诊断.方法:对患者的关节功能、X射线分期、休息痛、晨僵、压痛关节数、压痛关节指数、肿胀关节数、肿胀关节指数、日常生活能力、血沉、C-反应蛋白、类风湿因子、血红蛋白等指标进行评估.应用Pearson相关或Spearman等级相关分析类风湿因子分别与这些因子之间的相关性,其中对于服从正态分布的数据进行Pearson相关分析,对于非正态分布的数据进行Spearman相关分析.主要观察指标:类风湿因子分别与上述因子之间的相关性.结果:类风湿因子与年龄、病程、关节功能、X射线分期、休息痛、晨僵、压痛关节数、压痛关节指数、肿胀关节数、肿胀关节指数、日常生活能力、血沉、C-反应蛋白、血红蛋白之间的相关系数均无显著性差异(P＞0.05).结论:类风湿因子与类风湿关节炎疾病活动性和症状程度无相关性.     

类风湿性关节炎辨证分型与白细胞介素6、18血清水平的关系

目的:探讨白细胞介素6(IL-6)和白细胞介素18(IL-18)血清水平与类风湿性关节炎(RA)中医辨证分型的关系。方法:采用酶联免疫吸附试验(ELISA)双抗体夹心法检测RA患者和健康人的外周血IL-6和IL-18的血清水平,分析不同证型两指标之间及其与C反应蛋白、类风湿因子含量的相关性。结果:RA患者IL-6和IL-18血清水平与健康人比较差异具有显著性,活动期RA患者IL-6水平显著高于稳定期患者(P<0.05)。风寒湿阻型患者血清IL-6浓度明显高于痰瘀互结型与肝肾两虚型(P<0.05),而与风湿热郁型无明显差异(P>0.05);而风寒湿阻型患者血清IL-18浓度明显高于风湿热郁型与肝肾两虚型(P<0.05),而与痰瘀互结型无明显差异(P>0.05)。结论:IL-6血清水平与RA的活动性密切相关,且与其中医辨证分型存在一定的联系。     

Plasma growth differentiation factor‐15 in patients with “lone” atrial fibrillation

BackgroundGrowth differentiation factor‐15 (GDF‐15) is a member of the transforming growth factor β superfamily, correlated with various stimuli, including cardiovascular disease. The association between plasma GDF‐15 level and “lone” AF, that is, AF of unknown etiology (UeAF), is uncertain.MethodsAll patients aged 60 years or younger. AF patients were hospitalized for primary catheter ablation. Patients with sinus rhythm admitted for other diseases during the same period were included in the control group. ELISA was used to measure plasma GDF‐15 concentrations.Results60 UeAF patients, 60 paroxysmal AF (PAF) patients, and 70 control patients were enrolled. The mean age was 44.6 years. In the UeAF group, no patients had traditional clinical risk factors. The plasma GDF‐15 level in the UeAF group was (1028.5 ± 180.5) pg/ml, higher than in the control group, and moderately lower than in the PAF group. In all patients, positive correlations were found between plasma GDF‐15 level and age (R = 0.210, p < 0.05), and between plasma GDF‐15 level and left atrial diameter (LAD; R = 0.338, p < 0.05; in the UeAF group: R = 0.475, p < 0.05; in the PAF group: R = 0.504, p < 0.05).ConclusionsOur study first investigated the role of GDF‐15 in UeAF. The plasma GDF‐15 level in UeAF patients was higher than in sinus rhythm patients and lower than in PAF patients. Moreover, GDF‐15 was positively correlated with age and LAD. The role of GDF‐15 in UeAF needs further study.     

Tumor necrosis factor‐alpha stimulated gene‐6: A biomarker reflecting disease activity in rheumatoid arthritis

BackgroundTo explore the serum tumor necrosis factor‐alpha stimulated gene‐6 (TSG‐6) level and its association with disease activity in rheumatoid arthritis (RA) patients.MethodsWe recruited 176 RA patients, 178 non‐RA patients (lupus erythematosus, osteoarthritis, ulcerative colitis, ankylosing spondylitis and psoriasis) and 71 healthy subjects. Serum TSG‐6 levels were detected by enzyme‐linked immunosorbent assay (ELISA). RA patients were divided into inactive RA and active RA groups by disease activity score of 28 joints based on C‐reactive protein (DAS28‐CRP). The receiver operating characteristic (ROC) curve and Spearman''s rank correlation test analyzed the correlation between TSG‐6 concentration and RA disease activity.ResultsTumor necrosis factor‐alpha stimulated gene‐6 levels in the RA group were increased (p < 0.01). TSG‐6 concentrations indicated an upward tendency with increased disease activity; The area under the curve (AUC) of TSG‐6 for diagnosing RA and assessing the severity of RA were 0.78 and 0.80, respectively; The combination of TSG‐6 and anti‐mutated citrullinated vimentin antibodies (anti‐MCV) (sensitivity:98.4%)improved the diagnostic accuracy of RA. Binary logistic regression analysis showed that TSG‐6 was an independent risk factor related to the severity of RA, and OR (95% CI) was 1.2 (1.003–1.453).ConclusionThe TSG‐6 levels in RA patients were elevated and related to disease activity. Therefore, TSG‐6 may serve as a new potential biomarker for evaluating RA disease activity.     

Increased serum sialic acid levels in primary osteoarthritis and inactive rheumatoid arthritis

Accumulation of oxidized proteins and impaired antioxidant system have been shown to be associated with arthritis. Serum sialic acid (SA) is known as a parameter of inflammation. In the present study, to explore the potential role of SA in arthritis, we measured serum SA levels, plasma protein oxidation, and antioxidant status in patients with primary osteoarthritis (POA) and inactive rheumatoid arthritis (RA). Inactive RA (iRA) was defined upon the American College of Rheumatology criteria for clinical remission of RA. A total of 40 patients (20 POA patients, including 4 male subjects, and 20 iRA female patients) and 20 healthy female subjects were included in this study. SA, antioxidants, and protein oxidation levels were determined spectrophotometrically in serum or plasma samples. Serum SA levels were significantly increased in POA (3.34 +/- 0.37 mM, p < 0.0001) and iRA (3.11 +/- 0.47 mM, p < 0.05), compared with healthy controls (2.41 +/- 0.16 mM). Plasma total antioxidant activity, plasma superoxide dismutase activity and serum reduced glutathione levels were significantly decreased in patients with POA and those with iRA, whereas plasma carbonyl content and serum total protein were increased in those patients. Moreover, plasma total thiol levels were significantly increased in iRA and decreased in POA. Thus, increased SA and protein oxidation levels are associated with the decreased antioxidant levels in POA and iRA patients. These results suggest that SA may be considered as a potent defense molecule against oxidative damage in arthritis. Antioxidant therapy may halt or ameliorate the progression of arthritis.     

C-反应蛋白与类风湿关节炎疾病活动度的相关性研究

目的探讨C-反应蛋白(CRP)与类风湿关节炎疾病活动度的相关性。方法选择112例类风湿关节炎患者为观察组,其中62例为活动期患者,50例为非活动期患者,同时选择50例健康者为对照组,比较两组超敏C-反应蛋白(hs-CRP)、抗环瓜氨酸肽抗体(抗CCP)、类风湿因子(RF)及红细胞沉降率(ESR)的差别。结果观察组患者hs-CRP、抗CCP、RF及ESR水平明显高于对照组(P<0.01),活动期患者上述检测指标明显高于非活动期患者(P<0.01);观察组患者hs-CRP、抗CCP、RF与ESR显著相关(P<0.05)。结论 hs-CRP可作为类风湿关节炎疾病活动期的敏感指标之一,与抗CCP、RF及ESR联合检测对病情有预测价值。     

Serum leptin levels in rheumatoid arthritis and relationship with disease activity

OBJECTIVES: This study was performed to evaluate serum leptin levels in rheumatoid arthritis (RA) patients and investigate the correlation with serum tumor necrosis factor alpha (TNF-alpha) levels and clinical and laboratory parameters of disease activity. METHODS: Fifty patients with RA and 34 control subjects were included. Disease activity score 28 (DAS28) was calculated for each patient. Laboratory activity was assessed by examining erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Immunoradiometric assay was used for measuring serum leptin levels (ng/mL). Serum TNF-alpha levels (pg/mL) were measured by sandwich enzyme-linked immunosorbent assay method in 41 of 50 RA patients and in 24 control subjects. RESULTS: Age, sex and body mass index (BMI) did not show a statistically significant difference between RA and control subjects (P > 0.05). Serum leptin levels were higher in RA (P = 0.000). In RA patients, there were no correlations between serum leptin levels and disease duration, swollen and tender joint counts, DAS28, CRP, ESR, serum TNF-alpha levels, oral glucocorticoid and methotrexate usage (P > 0.05). There was no statistically significant serum leptin level difference between patients with high disease activity and mild and low disease activity (P = 0.892). Serum leptin levels positively correlated with BMI in both patient and control groups (P < 0.05). In both groups, mean serum leptin levels were higher in women than men. CONCLUSIONS: Even though serum leptin levels were found to be significantly higher in RA patients than in control subjects in this study, there was no correlation between serum leptin levels and TNF-alpha levels, clinical and laboratory parameters of disease activity. However serum leptin levels positively correlated with BMI in both patient and control groups. In RA, circulating leptin levels do not seem to reflect disease activity.     

The relationship between serial measures of disease activity and outcome in rheumatoid arthritis

Disease activity was measured annually over a median periodof 7 years (range 5–9) in a cohort of 127 patients withrheumatoid arthritis. The measurements were plotted, and thearea under the resultant curve measured. The relationship ofserial measures of disease activity (area under the curve) tooutcome (measured radiologically, functionally and by globalassessment) was investigated. A significant correlation wasfound between persistent disease activity and radiographic deterioration.Similar results were found for functional outcome, as measuredby Steinbrocker grade, health assessment questionnaire scoreor global assessment (by analogue score). Single measures ofdisease activity did not predict outcome. Although imprecise,current methods of measuring disease activity in RA, if measuredserially, are valuable in predicting outcome over a 5–10year period.     

类风湿性关节炎血清25-羟维生素D水平变化及意义

目的观察类风湿性关节炎(RA)患者血清25-羟维生素D[25-(OH)D]水平变化,并研究其临床意义。方法采用化学发光法检测60例RA患者(RA组)与60例健康人(对照组)外周血血清25-(OH)D。结果 RA组血清25-(OH)D水平为(34.37±8.87)nmol/L,对照组为(61.33±7.74)nmol/L,两组比较差异有统计学意义(t=-6.892,P0.05),RA患者血清25-(OH)D水平与RA患者年龄、体质量指数(BMI)、晨僵时间、关节压痛数(TJC)、关节肿胀数(SJC)、C反应蛋白(CRP)、红细胞沉降率(ESR)、疾病总体疼痛(VAS)评分、生活质量(HAQ)评分以及疾病活动度(DAS28)评分呈负相关(r=-0.201、-0.255、-0.362、-0.296、-0.273、-0.198、-0.323、-0.356、-0.379、-0.418,P0.05);与病程、类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体滴度等无相关性(P0.05)。结论 RA患者血清25-(OH)D水平明显低下,与RA疾病活动度相关。     

血清巨噬细胞移动抑制因子与类风湿关节炎活动性的关系

背景：巨噬细胞移动抑制因子作为肿瘤坏死因子a和白细胞介素1β的上游细胞因子，其调控作用在类风湿性关节炎发病机制中居重要地位。目的：分析血清巨噬细胞移动抑制因子与类风湿关节炎活动性的相关性。设计、时间及地点：非随机化同期对照及病例对照观察，于2005—09／200610在解放军白求恩国际和平医院完成。对象：选择门诊及住院类风湿性关节炎患者60例，另选同期健康者30例做对照组，其年龄、性别均与病例组匹配。方法：分析60例类风湿性关节炎患者的临床资料，根据DAS（disease activity score）积分将其分为类风湿性关节炎活动组及缓解组，并与30名正常人作对照。主要观察指标：①比较两组患者晨僵时间、关节压痛指数、关节肿胀指数、类风湿因子半定量、C反应蛋白、血沉、血小板计数。②采用双抗体夹心ELISA法检测血清巨噬细胞移动抑制因子浓度，比较类风湿性关节炎活动组、缓解组、健康对照组血清巨噬细胞移动抑制因子、白细胞介素1β、肿瘤坏死因子a水平。③分析类风湿性关节炎活动组血清巨噬细胞移动抑制因子水平与炎性指标、临床观察指标的相关性。结果：类风湿性关节炎活动组血清巨噬细胞移动抑制因子水平显著高于缓解组及正常对照组（P〈0．05），但缓解组较正常组差异无显著性意义（P〉0．05）。类风湿性关节炎活动组血清巨噬细胞移动抑制因子水平与炎性指标白细胞介素1β、肿瘤坏死因子α、血沉、C-反应蛋白、血小板计数以及关节肿胀指数和关节压痛指数均呈正相关，而与年龄、病程、晨僵时间和类风湿因子半定量则无相关性。结论：血清巨噬细胞移动抑制因子水平在类风湿性关节炎活动期显著增高，与炎性指标及关节肿痛呈正相关，提示可以作为类风湿性关节炎病情活动的血清标志物。     

类风湿关节炎患者血清炎症因子与骨质疏松的关系

目的探索及分析类风湿关节炎患者的血清白细胞介素-34(IL-34)、类风湿因子(RF)、细胞核因子κB受体活化因子配体(RANKL)等指标水平变化,且观察其变化与骨质疏松的关系。方法收集2016年1月至2017年1月间该院接收的患类风湿关节炎的40例患者作为研究组,同时取同期于本院进行健康体检的40例健康人群作为对照组。通过酶联免疫吸附试验(ELISA)对2组对象的血清IL-34、RANKL水平进行检测,通过乳胶凝集法对2组对象的血清RF水平进行检测,同时常规检测患者的骨密度(BMD)、红细胞沉降率(ESR)、C反应蛋白(CRP)、抗CCP抗体,并经改良DAS28评分对类风湿关节炎的疾病活动度进行评估。结果研究组的血清IL-34、RF及RANKL等指标水平高于对照组,BMD低于对照组,且差异均具有统计学意义(P0.05);研究组的骨质疏松发生率大于对照组,差异具有统计学意义(P0.05);研究组中骨质疏松患者的IL-34、RF、RANKL水平高于骨量正常组,差异具有统计学意义(P0.05);经Spearman秩相关分析发现,研究组的血清IL-34水平与ESR、CRP、抗CCP抗体及DAS28评分等指标均呈正相关(P0.05),血清IL-34、RF及RANKL水平与BMD呈均呈负相关(P0.05)。结论类风湿关节炎患者的血清IL-34、RF、RANKL水平均有明显上升,且以上指标均与BMD呈负相关,提示可能IL-34协同参与了骨质疏松的出现。