Soluble receptors of TNF-alpha with molecular mass 55 kDa in rheumatoid arthritis: clinical role

To evaluate clinical implications of the serum level of soluable receptors of tumor necrosis factor alpha (TNFa) with molecular mass 55 kDa (rTNF-55R) in rheumatoid arthritis, serum levels of rTNF-55R and rTNF-75R were measured with the use of radioimmunoassay in 76 RA patients, 38 donors and in 25 RA patients, 10 donors, respectively. RESULTS: Elevated serum level of rTNF-55R was recorded in 55.3% RA patients. This level correlated with basic clinical and laboratory parameters of RA, the disease activity, values of DAS indices. It is concluded that a serum level of rTNF-55R adequately reflects clinico-laboratory activity of RA and its measurement can be used for assessment of RA activity and treatment efficiency.     

Soluble interleukin-2 receptor: elevated levels in serum and synovial fluid of patients with rheumatoid arthritis

Soluble interleukin-2 receptor (sIL-2R) levels were quantitated in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and degenerative joint disease (DJD). A sandwich immunoassay, employing two monoclonal antibodies against distinct epitopes on the IL-2R, was utilized for measurement. We found a striking elevation of sIL-2R in RA SF as compared with DJD SF (RA, 1319 +/- 135; DJD, 416 +/- 59; p less than 0.001). RA serum sIL-2R levels were also significantly elevated over DJD levels. There was no interaction between rheumatoid factor (RF) and sIL-2R. RA patients with elevated sIL-2R levels had significantly longer disease duration, higher c-reactive protein (CRP) levels in serum and SF, and higher RF levels in serum and SF. The groups were similar in regard to other laboratory variables. The presence of elevated levels of sIL-2R in RA serum and SF confirms the presence of a heightened immune reactivity and in vivo activation of lymphocytes in RA.     

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.     

类风湿性关节炎患者血清白细胞介素的检测

为了解类风湿性关节炎（ＲＡ）患者的免疫损伤机理，应用酶联免疫吸附法（ＥＬＩＳＡ）检测３８例ＲＡ患者血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）和白细胞介素８（ＩＬ－８）含量，并检验其相关性。结果：（１）ＲＡ患者血清ｓＩＬ－２Ｒ和ＩＬ－８水平均比正常对照组显著升高（Ｐ＜０．０１）；血清ｓＩＬ－２Ｒ浓度在类风湿因子（ＲＦ）阳性与阴性组中差异有显著性（Ｐ＜０．０１）；（２）ＲＦ阳性患者血清ｓＩＬ－２Ｒ与ＩＬ－８浓度呈正相关（ｒ＝０．７４，Ｐ＜０．０５）。提示ＲＡ患者Ｔ细胞异常活化以及免疫调节功能紊乱。     

葡萄糖-6-磷酸异构酶在诊断类风湿关节炎中的意义

目的 探讨类风湿关节炎(BA)患者外周血单个核细胞(PBMC)中葡萄糖-6-磷酸异构酶(GPI)mRNA及血清中GPI抗原表达与RA发病机制及活动性的关系,分析比较GPI与抗突变型瓜氨酸波形蛋白(MCV)抗体、抗环瓜氨酸多肽(CCP)抗体、类风湿因子(RE)在RA诊断中的价值.方法 用实时荧光定量逆转录(FQ-RT)-PCR检测60例RA患者(活动期28例、缓解期32例)、30例其他风湿性疾病患者、30名健康体检者PBMC中GPI mRNA的表达水平和含量[以△Ct=Ct1(待测基因)-Ct2(内参基因)来比较基因表达水平的高低];同时用ELISA检测各组血清中GPI和抗MCV抗体,抗CCP抗体和RF水平.结果 RA患者GPI mRNA表达水平[△Ct=4.21(3.04～7.23)]明显高于其他风湿性疾病组[△Ct=8.42(5.16～9.98),P<0.01]和健康对照组[△Ct=8.66(4.90～10.01),P<0.01],活动期组GPI mRNA表达水平[△Ct=3.78(1.28～6.09)]与缓解期组[△Ct=5.88(3.23～8.94)]的差异有统计学意义(H=11.760,P<0.01);RA组血清GPI水平[3.02(2.02～8.39)mg/L]明显高于其他风湿性疾病组[0.20(0.11～0.32)mg/L]和健康对照组[0.18(0.08～0.30)mg/L],且RA活动期组血清GPI水平[4.84(2.81～10.38)mg/L]与缓解期组[2.12(1.26～4.34)mg/L]差异也有统计学意义(H=9.830,P<0.01).同时检测GPI、抗MCV抗体和抗CCP抗体对RA的敏感度分别为68%(41/60)、57%(34/60)、58%(35/60);特异度分别为95%(57/60)、92%(55/60)、93%(56/60).结论 GPI mRNA可能参与了RA的发病过程,并与疾病的活动性相关,血清中GPI对RA诊断有相对较高的敏感度和特异度,可作为临床诊断RA的辅助指标.     

Clinical value of soluble tumor necrosis factor-alpha receptors in patients with systemic lupus erythematosus

The study was undertaken to examine the clinical value of serum levels of soluble receptors of tumor necrosis factor-alpha with a molecular mass of 55 kDa (rTNF-alpha-55R) in patients with systemic lupus erythematosus (SLE). The serum level of rTNF-alpha-55R was measured by enzyme immunoassay (a "Quantikine" set, R&D System, USA) in 73 patients with SLE and 22 donors. In the patients, the mean level of rTNF-alpha-55R was significantly higher than that in donors. Higher serum levels of rTNF-alpha-55R were noted in 43.8% of the patients with SLE. There was a correlation between the level of rTNF-alpha-55R and the progression of SLE (p < 0.05), the exacerbation (p < 0.05), and the clinical manifestations of the disease (cardiac valvular apparatus damage, active lupus nephritis). rTNF-alpha-55R are a marker of the progression and exacerbation of SLE and reflects that there is a prognostically poor factor, i.e. the involvement of the kidneys in a pathological process.     

血清胞苷脱氨酶检测对类风湿关节炎早期诊断的价值

目的探讨测定血清中的胞苷脱氨酶活性对类风湿关节炎患者的诊断价值。方法采用分光光度法测定血清中的胞苷脱氨酶活性。结果正常对照组血清中的胞苷脱氨酶活性没有性别和年龄差异(30名男性:4.89±1.96U/ml,30名女性:4.82±1.72U/ml),63名类风湿性关节炎患者血清胞苷脱氨酶活性为12.51±2.71U/ml,与正常人群比较有显著性差异(P<0.001),且显著高于风湿性关节炎患者(P<0.001),36名风湿性关节炎患者血清中的胞苷脱氨酶活性为5.03±1.83U/ml,与正常对照组比较无显著差异(P<0.05)。结论胞苷脱氨酶活性可作为类风湿关节炎急性感染的早期诊断指标,且在风湿性关节炎与类风湿性关节炎的鉴别诊断中具有重要意义,对类风湿关节炎的预后判断亦有临床价值。     

类风湿关节炎患者外周血白细胞介素-32的表达及临床意义

目的分析类风湿关节炎(RA)患者外周血白细胞介素-32(IL-32)的表达及临床意义。方法选取122例RA患者,根据活动度积分(DAS28)将其分为高活动组45例(DAS285.1)、中低活动组42例(DAS28≥2.6~≤5.1)和缓解期组35例(DAS282.6)。选取同期50例非RA结缔组织病患者作为非RA组,选取同期50名健康志愿者作为对照组。对5组研究对象血清IL-32、TNF-α水平及外周血单核细胞(PBMC)中的IL-32、TNF-α基因相对表达量进行检测和比较。结果高活动组患者PBMC中IL-32、TNF-αmRNA相对表达量和血清IL-32、TNF-α水平最高,其次为中低活动组患者,非RA组患者的血清TNF-α水平显著高于缓解期组和对照组(P0.05)。缓解期、非RA组和对照组PBMC中IL-32、TNF-αmRNA相对表达量和血清IL-32水平的差异均无统计学意义(P0.05),缓解期组和对照组研究对象的血清TNF-α水平的差异无统计学意义(P0.05)。RA患者血清和PBMC中的IL-32、TNF-α水平与RA患者的病情指标均具有相关性(P0.05)。结论 RA患者表现为外周血IL-32水平的显著升高,其水平与其疾病严重程度和活动性程度指标具有相关性,提示了IL-32可能在RA的活动性增强过程中具有重要的作用,可作为评价RA病情的辅助指标。     

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。     

Alpha-2 macroglobulin in serum and synovial fluid of patients with rheumatoid arthritis and osteoarthrosis

AIM: To study concentrations of alpha-2-macroglobulin (A-2-MG) in blood serum and synovial fluid (SF) in patients with rheumatoid arthritis and formulation of basic clinical, laboratory and x-ray criteria of RA activity. MATERIALS AND METHODS: A-2-MG levels were measured in the serum and SF from 151 RA patients and in the serum of 20 patients with osteoarthrosis (OA) and 62 healthy donors. The serum concentration for RA patients was 166 +/- 65.3 mg%, for OA patients--175.26 +/- 36.99 mg% and for healthy donors--177.772 +/- 50 mg%. Mean concentration of SF A-2-MG in RA patients was 98.77 +/- 82.43 mg%. CONCLUSION: Changes in the concentration of A-2-MG are unrelated to inflammation activity in the joints of RA and OA patients. Serum and synovial concentration of this protein corresponds to changes in the concentration of IgM and rheumatoid factors in RA patients.     

Soluble adhesion molecules (P-selectin, ICAM-1 and ICAM-3) in rheumatoid arthritis]

AIM: Investigation of serum levels and clinical role of soluble intercellular molecules of adhesion (pICAM-1, PICAM-3 and pP-selectin) in rheumatoid arthritis (RA). MATERIALS AND METHODS: Enzyme immunoassay with Bender MedSystem kits (Austria) was employed to measure serum concentration of soluble intercellular molecules of adhesion in 36 RA patients. RESULTS: Elevated levels of serum pICAM-1, pICAM-3 and pP-selectin were registered in 74.2, 28.6 and 25.7% of RA patients, respectively. Content of pP-selectin more strongly correlated with activity and severity indices than that of pICAM-3 (p < 0.001). Content of pICAM-1 and clinical picture of RA were unrelated. CONCLUSION: Levels of pP-selectine can characterize RA activity.     

白细胞介素-21及其受体在类风湿关节炎患者血清及外周血单个核细胞中的表达

目的检测类风湿关节炎(RA)患者血清、外周血单个核细胞(PBMC)中白细胞介素-21(IL-21)及其受体(IL-21R)的表达水平,探讨二者之间的相关性及其在RA病理机制中的作用。方法血清IL-21含量采用酶联免疫吸附试验检测,套式实时荧光定量聚合酶链反应法测定PBMC中IL-21R mRNA水平。结果 RA患者组血清中IL-21含量和PBMC中IL-21RmRNA表达水平均高于健康对照组,差异有统计学意义(P<0.01);RA活动期IL-21、IL-21RmRNA水平明显高于非活动期,RA患者经治疗症状改善者IL-21、IL-21R含量明显下调,分别下降21.0%、30.3%,治疗前后比较差异有统计学意义(P<0.01);IL-21和IL-21R表达水平与RA患者关节功能分级有显著相关性,Ⅲ级以上与Ⅰ级、Ⅱ级相比2项指标差异有统计学意义(P<0.01)。结论 IL-21与IL-21R水平检测对RA的诊断和治疗有重要的临床意义。     

程序性细胞死亡因子5在活动性类风湿关节炎患者中的水平变化

目的：探究程序性细胞死亡因子5（programmed cell death factor 5,PDCD5）在类风湿关节炎（rheumatoid arthritis, RA）患者中的表达情况,并探讨PDCD5在RA发病中的可能作用。方法：采用酶联免疫吸附试验检测36例活动性RA患者和35例骨关节炎（osteoarthritis,OA）患者的血清和关节液中的PDCD5、白细胞介素6（interleukin 6,IL-6）水平,另以33名健康人的血清PDCD5水平作为对照（对照组）,比较3组间以上各指标水平的差异。同时再检测RA患者的C反应蛋白（C reaction protein, CRP）、红细胞沉降率（erythrocyte sedimentation rate, ESR）、类风湿因子（rheumatoid factor,RF）和环瓜氨酸肽（cyclic citrullinated peptide, CCP）,记录其肿胀关节数（swollen joint count,SJC）、疼痛关节数（tender joints count, TJC）,作为疾病活动指数参考指标。结果：RA组的血清PDCD5水平[（32.47±12.79） ng/mL]显著高于OA组[（12.79±9.84） ng/mL]及对照组[（18.40±18.97） ng/mL];RA组关节液中的PDCD5水平[（47.75±21.94） ng/mL]亦高于OA组[（19.33±11.25） ng/mL]。RA患者血清中的PDCD5水平与IL-6水平呈负相关（r=-0.431）,但在关节液中未观察到两者间具有相关性。Pearson分析显示,RA患者血清中的PDCD5水平与CRP、ESR、SJC、TJC呈负相关（R值分别为-0.523、-0.701、-0.845、-0.943）,但与CCP及RF水平间无统计学相关性。结论：活动性RA患者的血清及关节液中PDCD5的水平升高,而其表达失调可能与IL-6水平相关。     

Neopterin: new immunological marker of autoimmune rheumatic disease

Serum neopterin (SN), concentration of soluble (s) TNF-receptors (R) with molecular mass 55 kD and sIL-2R, C-reactive protein (CRP), Willebrand factor antigen (WF Ag) were measured in enzyme immunoassay (EIA) or radioimmunoassay (BRAHMS, Berlin, Germany) in 189 patients with autoimmune rheumatic diseases: 52 patients with systemic lupus erythematosus (SLE), 67 patients with rheumatoid arthritis (RA), 44 patients with polymyositis/dermatomyositis and 26 patients with Wegener granulomatosis. SN appeared elevated in autoimmune rheumatic diseases correlating with the disease activity and concentrations of sTNF R and sIL 2R. Assay for neopterin is clinically essential for examination of the immunopathological process activity, prediction of the outcomes, better knowledge about cytokine synthesis profile in autoimmune rheumatic diseases.     

Evidence for locally synthesized and clonally restricted immunoglobulin in the synovial fluid from rheumatoid arthritis patients

In this study, we examined the immunoglobulin (Ig) present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) to determine if it was locally produced and to assess the presence of clonally restricted (oligoclonal) immunoglobulin. We studied SF/serum pairs from 55 RA patients and 23 patients with degenerative joint disease (DJD). We found increases in total protein, IgG, IgA, and IgM in RA vs DJD SF (P less than 0.01). The immunoglobulin present in RA appeared to be locally produced as evidenced by significant increases (P less than 0.01) in the immunoglobulin indices. Regression analysis among the levels of IgG, IgA, and IgM RF and the Ig indices suggested that only a minority of the locally synthesized Ig present was specific for RF. To provide evidence of clonal restriction, we further analyzed the SF specimens by isoelectric focusing and assessed the presence of oligoclonal bands present only in RA SF. In 7/55 RA specimens (13%) we found unique SF IgG bands. All bands were of similar isoelectric point (pI), being quite cathodic with pI greater than 7.5. Our evidence supports synthesis of Ig within RA synovium, with a minority of patients showing prominent and unique SF Ig bands. This suggests an oligoclonal response in SF of some patients, but polyclonal Ig synthesis in most.     

Alteration of tryptophan metabolism in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis

Tryptophan, its metabolites and related enzyme activity in synovial fluid, blood and urine in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were measured. The levels of tryptophan, kynurenine and anthranilic acid in the synovial fluid higher in RA were than in OA, whereas the xanthurenic acid level was equal in RA and OA. Indoleamine 2, 3-dioxygenase activity in the synovial membrane was higher in RA than in OA. 5-Hydroxytryptamine (5-HT) levels in the synovial fluid and the blood and the 5-hydroxyindole acetic acid (5-HIAA) level in the synovial fluid were essentially the same for both diseases. However, the 5-HIAA level in the serum of RA patients was higher than in those with OA, and the 5-HIAA level in the urine of RA patients was lower than in those with OA. In addition, monoamine oxidase-A and B activity in the synovial fluid of RA patients was decreased than in those with OA. These findings suggest that metabolism of tryptophan is altered in patients with RA.     

类风湿关节炎表皮生长因子及β_2微球蛋白的测定

目的　探讨表皮生长因子 (EGF)与 β2 微球蛋白 ( β2 M )在类风湿关节炎 (RA)发病机理及诊断中的意义。方法　用放射免疫分析法 (RIA)测定 71例RA患者血清EGF、β2 M。结果　RA患者血清EGF、β2 M显著升高 ,说明EGF、β2 M在RA的发病中可能起一定作用 ,但与RA的活动性无关。     

RA患者免疫功能失衡与疾病活动情况的关系研究

目的探讨类风湿关节炎(RA)患者免疫功能失衡与患者疾病活动程度的关系。方法选取我院类风湿免疫科确诊的RA患者90例(RA组)、健康体检志愿者60例作为对照组;检测两组对象外周血中Th17细胞、调节性T细胞(Treg)、血清γ干扰素(IFN-γ)、白细胞介素-4(IL-4)、C反应蛋白(CRP)、血沉(ESR),并分析Th17细胞、Treg、IFN-γ、IL-4与患者关节疼痛数目、类风湿关节炎病情评价(DAS28评分)的相关性。结果 RA组患者的Th17细胞、血清IFN-γ均高于对照组(P<0.05),RA组患者的Treg细胞低于对照组(P<0.05);RA组患者的血清CRP、ESR水平均高于对照组(P<0.05);DAS28评分>5.1分RA患者的Th17细胞、血清IFN-γ均高于≤5.1分的患者(P<0.05),DAS28评分>5.1分RA患者的Treg细胞低于≤5.1分的患者(P<0.05);RA患者的Th17细胞、血清IFN-γ与DAS28评分、压痛关节数目呈显著正相关(P<0.05),RA患者的Treg细胞与DAS28评分、压痛关节数目呈显著负相关(P<0.05)。结论 RA患者T细胞及免疫学因子失衡可能与患者疾病活动程度、病情严重程度有关。     

肿瘤坏死因子α,γ干扰素和红细胞生成素与类风湿性关节 …

目的 探讨类风湿性关节炎（ＲＡ）伴慢性病性贫血（ＡＣＤ）的特征,及肿瘤坏死因子α（ＴＮＦα）、γ干扰素（ＩＦＮ－γ）和红细胞生成素（Ｅｐｏ）在其发病中的作用。方法 采用ＥＬＩＳＡ法检测ＲＡ患者血清ＴＮＦα、ＩＦＮ－γ水平及ＲＡ伴ＡＣＤ虱的血清Ｅｐｏ产生的影响及ＴＮＦα、ＩＦＮ－γ和Ｅｐｏ对正常骨髓ＣＦＵ－Ｅ和ＢＦＵ－Ｅ的影响;以及ＲＡ自身血清、Ｅｐｏ对ＲＡ骨髓ＣＦＵ－Ｅ的影响。结果 与正常对照组比     

Serum progranulin level is associated with disease activity following orthopedic surgery in rheumatoid arthritis patients

BackgroundFew studies have focused on the ability of progranulin to predict postoperative disease activity in rheumatoid arthritis (RA) patients who have undergone surgery. This study evaluated serum progranulin levels in active RA patients and analyzed its relationship with postoperative disease activity.MethodsOne hundred thirty-two patients with active RA and 72 healthy subjects were included in this study. Serum progranulin was measured, and clinical data were collected. The postoperative 1-year Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) scores was evaluated as an indicator of disease activity. The predictive value of progranulin in postoperative 1-year disease activity in RA patients was also analyzed.ResultsSerum progranulin was significantly associated with the postoperative 1-year RA disease activity. The mean serum progranulin level in patients with a high disease activity was significantly higher than that of RA patients with low-to-moderate disease activity (54.2 ± 10.6 ng/mL vs. 46.7 ± 8.8 ng/mL). Serum progranulin was also evaluated as an independent predictive factor for postoperative 1-year RA disease activity in multivariate analysis (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.02–8.85).ConclusionsSerum progranulin levels may be a promising indicator of postoperative disease activity in RA patients who underwent orthopedic surgery.