抗CCP、抗RA33等4种自身抗体在类风湿关节炎诊断中的应用

目的探讨类风湿关节炎(RA)患者检测血清抗环瓜氨酸肽(CCP)抗体、抗RA33抗体、抗角蛋白抗体(AKA)的临床意义.方法采用ELISA检测抗CCP和抗RA33,间接免疫荧光法检测AKA,免疫比浊法检测类风湿因子(RF).共检测46例RA患者、30例系统性红斑狼疮(SLE)患者、24例骨关节炎(OA)患者和30名正常对照.结果 46例RA患者中抗CCP、抗RA33、AKA和RF的阳性率分别为52.2%(24/46)、17.8%(8/46)、21.7%(10/46)和69.6%(32/46).而30例SLE患者其阳性率分别为3.3%(1/46)、6.7%(2/46)、0%(0/46)和26.7%(8/46),24例OA患者无一例阳性.30名正常对照者中仅1例抗CCP阳性,其余指标均为阴性.结论抗CCP、抗RA33和AKA均是RA特异性诊断指标,但三者与RF可相互补充,选择适当的指标联合检测有助于提高诊断的敏感性和特异性.     

AKA、APF及抗CCP联合检测与类风湿关节炎的早期诊断

目的联合检测类风湿关节炎(RA)患者血清中的抗环瓜氨酸抗体(CCP)和抗角蛋白抗体(AKA)、抗核周因子抗体(APF),探讨RA的早期诊断方法。方法对已确诊的71例RA患者、207例非RA的自身免疫病患者同时测定抗CCP抗体(ELISA法)和AKA、APF(间接免疫荧光法)。结果AKA、APF及抗CCP抗体对早期RA的敏感性分别为46.5%、77.5%和69.0%;特异性分别为100%、100%和98.8%。CCP及APF的阳性检出率高于AKA(p<0.01)而与类风湿因子(RF)无差异(p=0.067).RF弱阳性或阴性的RA患者,AKA、APF及CCP可为阳性。结论CCP抗体及APF对RA具有较好的敏感性和高度的特异性,联合检测AKA、APF、CCP抗体可作为早期RA病人及RF阴性RA病人的早期诊断指标。     

抗CCP、抗RA33等4种自身抗体在类风湿关节炎诊断中的应用

目的　探讨类风湿关节炎 (RA)患者检测血清抗环瓜氨酸肽 (CCP)抗体、抗RA33抗体、抗角蛋白抗体(AKA)的临床意义。方法　采用ELISA检测抗CCP和抗RA33,间接免疫荧光法检测AKA ,免疫比浊法检测类风湿因子 (RF)。共检测 4 6例RA患者、30例系统性红斑狼疮 (SLE)患者、2 4例骨关节炎 (OA)患者和 30名正常对照。结果　 4 6例RA患者中抗CCP、抗RA33、AKA和RF的阳性率分别为 5 2 .2 % (2 4 / 4 6 )、17.8% (8/ 4 6 )、2 1.7% (10 / 4 6 )和 6 9.6 % (32 / 4 6 )。而 30例SLE患者其阳性率分别为 3.3% (1/ 4 6 )、6 .7% (2 / 4 6 )、0 % (0 / 4 6 )和2 6 .7% (8/ 4 6 ) ,2 4例OA患者无一例阳性。 30名正常对照者中仅 1例抗CCP阳性 ,其余指标均为阴性。结论　抗CCP、抗RA33和AKA均是RA特异性诊断指标 ,但三者与RF可相互补充 ,选择适当的指标联合检测有助于提高诊断的敏感性和特异性。     

RF、抗CCP抗体、抗AKA及CRP联合检测在类风湿关节炎诊断中的应用价值

目的探究类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体、抗角蛋白抗体(AKA)及C反应蛋白(CRP)联合检测用于类风湿关节炎(RA)的诊断价值。方法选择2016年12月至2019年1月于该院住院治疗的65例RA患者及62例非RA的自身免疫性疾病患者作为研究对象,测定两组患者RF、抗CCP抗体、抗AKA及CRP水平,比较两组患者各项指标阳性表达情况,分析各项指标单项或联合检测的诊断效能。结果 RA组患者RF、抗CCP抗体、抗AKA、CRP阳性率均明显高于非RA组,差异均有统计学意义(P<0.05);抗AKA、抗CCP抗体对RA的诊断特异度高于RF、CRP,RF对RA的诊断特异度高于CRP,差异均有统计学意义(P<0.05);RF联合CRP、抗CCP抗体联合抗AKA、抗CCP抗体联合CRP、抗AKA联合CRP及3项指标联合、4项指标联合诊断的灵敏度明显高于单项指标检测;联合检测中,抗CCP抗体+抗AKA诊断的特异度及准确度最高;4项指标联合诊断的灵敏度、特异度、准确度、阳性预测值、阴性预测值分别为92.31%、40.32%、66.93%、61.86%、83.33%。结论 RF、抗CCP抗体、抗AKA及CRP对RA具有一定的诊断价值,4项指标联合检测可提高灵敏度及特异度,可提高RA的早期诊断效能。     

抗环瓜氨酸肽抗体、抗角质蛋白抗体和类风湿因子在类风湿性关节炎诊断中的意义

目的 探讨抗环瓜氨酸肽(CCP)抗体、抗角质蛋白(AKA)抗体和类风湿因子(RF)对类风湿性关节炎(RA)诊断的临床意义.方法 分别应用ELISA、间接免疫荧光法及速率散射比浊法检测42例类风湿性关节炎患者的抗CCP抗体、AKA和RF,计算其灵敏度、特异性,并采用Kendall' Tau-b检验进行相关分析.结果 42例RA患者抗CCP抗体、AKA和RF的灵敏度和特异性分别为54.7%、97.37%;30.9%、97.37%;85.7%、78.95%,经统计学分析,抗CCP抗体与AKA存在相关性,而抗CCP抗体与RF之问不存在相关性.结论 抗CCP抗体有较高的灵敏度和特异性,是RA较好的诊断指标.联合检测抗CCP抗体、AKA和RF有利于提高RA的早期诊断率.     

3项联合检测对类风湿关节炎的诊断价值

目的探讨类风湿因子(RF)、抗环瓜氨酸多肽抗体(抗CCP)和抗角蛋白抗体(AKA)在类风湿关节炎(RA)中联合检测的价值。方法采用化学发光方法测定抗CCP,采用间接免疫荧光法检测AKA,采用免疫比浊法测定RF。结果抗CCP的阳性率在RA患者中为65.45%,在非RA中为3.33%,并且3项指标对RA诊断的敏感性和特异性分别为抗CCP 65.45%;97.83%,AKA 33.64%、96.83%;RF 75.45%、78.98%。RA患者的3项指标阳性率均明显高于非RA患者和健康体检者,差异有统计学意义(P<0.05)。结论抗CCP具有较好的灵敏度和特异性;联合检测抗CCP、AKA与RF可明显提高对RA诊断的特异性。     

抗环瓜氨酸肽抗体、抗角质蛋白抗体和类风湿因子在类风湿性关节炎诊断中的意义

目的探讨抗环瓜氨酸肽(CCP)抗体、抗角质蛋白(AKA)抗体和类风湿因子(RF)对类风湿性关节炎(RA)诊断的临床意义。方法分别应用ELISA、间接免疫荧光法及速率散射比浊法检测42例类风湿性关节炎患者的抗CCP抗体、AKA和RF,计算其灵敏度、特异性,并采用Kendall’Tau-b检验进行相关分析。结果42例RA患者抗CCP抗体、AKA和RF的灵敏度和特异性分别为54.7%、97.37%;30.9%、97.37%;85.7%、78.95%,经统计学分析,抗CCP抗体与AKA存在相关性,而抗CCP抗体与RF之间不存在相关性。结论抗CCP抗体有较高的灵敏度和特异性,是RA较好的诊断指标,联合检测抗CCP抗体、AKA和RF有利于提高RA的早期诊断率。     

自身抗体检测在类风湿关节炎的临床诊断价值评价

目的研究类风湿因子(RF),抗环瓜氨酸肽(CCP)抗体,抗角蛋白抗体(AKA)三种自身抗体联合检测在类风湿关节炎(RA)中的临床诊断价值。方法抗CCP抗体采用酶联免疫吸附实验,AKA采用间接免疫荧光法,RF采用速率散射比浊法。检测240例病人血清中的RF,抗CCP抗体和AKA。结果 RF,抗CCP抗体和AKA三个特异性指标在RA组阳性率分别为78.7%,77.3%,63.4%明显高于非RA组,差异有统计学意义(P<0.05)。RF,抗CCP抗体和AKA在类风湿关节炎的诊断中灵敏度分别为78.7%、77.3%、63.3%,特异度为77.8%、92.2%、98.8%,阳性预测值85.5%、94.3%、98.9%,阴性预测值68.6%、70.9%、61.8%,阳性似然比3.55、9.91、52.75,阴性似然比0.27、0.25、0.37,诊断符合率78.3%、82.9%、76.7%。将三者串联检测的灵敏度和特异度为59.3%和98.9%。三者并联检测的灵敏度和特异度为87.3%和70.0%。结论在RA的诊断中RF,抗CCP抗体和AKA有较高的特异性和灵敏度,尤其是抗CCP抗体的诊断评价指标最好。三个指标串联检测可以提高特异度减少误诊率,三个指标并联检测可以提高灵敏度降低漏诊率,因此三个指标联合检测指导临床对RA的早期诊断具有重要价值。     

抗环瓜氨酸肽抗体、类风湿因子与抗角蛋白抗体在类风湿关节炎诊断中的价值比较

目的比较抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)与抗角蛋白抗体(AKA)在类风湿性关节炎(RA)诊断中的作用。方法对118例(RA 61例,非RA 57例)患者血清同时进行抗CCP抗体、RF和AKA检测,检测方法分别为酶联免疫吸附试验(ELISA)、BECKMAN全自动蛋白分析仪、间接免疫荧光法。结果RA组中3种抗体的阳性率显著高于非RA组(P<0.01);抗CCP抗体对RA诊断的敏感性(67.2%)明显高于AKA(41.6%,P<0.01),且两者显著相关(P=0.004),与RF(77.0%)差异无显著性;抗CCP抗体对RA诊断的特异性(94.7%)明显高于RF(73.7%,P<0.01)与AKA(91.2%),差异无显著性;抗CCP抗体和RF联合检测的敏感性达90.2%。结论抗CCP抗体有适度的敏感性和很高的特异性,对诊断RA具有良好的应用价值;联合检测抗CCP抗体和RF具有更高的敏感性。     

抗角蛋白抗体与抗环瓜氨酸肽抗体在早期类风湿关节炎诊断中的意义比较

目的比较抗角蛋白（antikeratin antibody,AKA）抗体与抗环瓜氨酸肽（cyclic citrullinated peptides,CCP）抗体在早期类风湿关节炎诊断中的意义。方法对40例类风湿关节炎（rheumatoid arthritis,RA）患者、40例非RA患者和40例健康人采用酶联免疫吸附法（ELISA）检测抗CCP抗体,用免疫比浊法检测类风湿因子（rheumatoid factor,RF）,用间接免疫荧光法检测抗AKA抗体,并作比较。结果RA患者抗CCP抗体、抗AKA抗体、RF阳性率分别为82．5％、67．5％、90％,敏感性分别为82．5％、67．5％、90％,特异性分别为97．2％、95％、80％;非RA患者抗CCP抗体、AKA、RF的阳性率为分别2．5％、5％、32．5％;正常对照组1例抗CCP抗体弱阳性,2例AKA低滴度阳性。结论抗CCP抗体及AKA均为早期类风湿关节炎特异性诊断指标,但抗CCP抗体敏感性及特异性高于AKA,联合检测抗CCP抗体、AKA、RF有利于RA的早期诊断。     

A proinflammatory role for IL-18 in rheumatoid arthritis

IL-18 is a novel cytokine with pleiotropic activities critical to the development of T-helper 1 (Th1) responses. We detected IL-18 mRNA and protein within rheumatoid arthritis (RA) synovial tissues in significantly higher levels than in osteoarthritis controls. Similarly, IL-18 receptor expression was detected on synovial lymphocytes and macrophages. Together with IL-12 or IL-15, IL-18 induced significant IFN-gamma production by synovial tissues in vitro. IL-18 independently promoted GM-CSF and nitric oxide production, and it induced significant TNF-alpha synthesis by CD14(+) macrophages in synovial cultures; the latter effect was potentiated by IL-12 or IL-15. TNF-alpha and IFN-gamma synthesis was suppressed by IL-10 and TGF-beta. IL-18 production in primary synovial cultures and purified synovial fibroblasts was, in turn, upregulated by TNF-alpha and IL-1beta, suggesting that monokine expression can feed back to promote Th1 cell development in synovial membrane. Finally, IL-18 administration to collagen/incomplete Freund's adjuvant-immunized DBA/1 mice facilitated the development of an erosive, inflammatory arthritis, suggesting that IL-18 can be proinflammatory in vivo. Together, these data indicate that synergistic combinations of IL-18, IL-12, and IL-15 may be of importance in sustaining both Th1 responses and monokine production in RA.     

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IL-18检测的影响因素分析

目的探讨不同的保存时间、温度对类风湿关节炎(RA)患者外周血与关节积液IL-18水平的影响。方法将12例RA患者的血清与关节积液按照不同保存时间与温度条件分为A组(血清,室温0h)、B组(全血,室温36h)、C组(全血,室温72h)、D组(全血,4℃72h)、E组(血清,室温72h)、F组(关节液,室温0h)、G组(关节液,室温72h),用ELISA检测各组IL-18浓度变化。结果 B、D、E组IL-18浓度明显高于A组(均P<0.05);F组IL-18浓度与A组比较差异无统计学意义(P>0.05)。非参数两关联样本检验显示C组IL-18浓度明显高于A、B、D组;G组IL-18浓度明显高于F组(P<0.05)。结论外周血及关节积液IL-18水平变化趋势一致,IL-18检测受时间和温度影响,且温度影响更显著。     

Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis.

By using a sandwich ELISA, soluble human IL-6 receptor (sIL-6 R) levels were measured in the sera of 20 healthy children and of 25 patients with systemic juvenile rheumatoid arthritis (JRA). In patients with systemic JRA, serum sIL-6 R levels (114.6 +/- 37.7 ng/ml) were significantly lower (P < 0.01) than those of healthy children (161.2 +/- 45.5 ng/ml). Serum sIL-6 R levels were negatively correlated (r = -0.610, P < 0.001) with serum IL-6 levels measured with the B9 cells. The serum IL-6/sIL-6 R complex was detected using an ELISA based on a monoclonal antibody to IL-6 for capture and on a monoclonal antibody to human sIL-6 R for detection. Healthy controls had little, if any, detectable serum IL-6/sIL-6 R complex (OD 0.024 +/- 0.027), while the majority of patients with systemic JRA presented measurable serum IL-6/sIL-6 R complex (OD 0.492 +/- 0.546). IL-6 levels estimated in the circulating IL-6/sIL-6 R complexes were in the range of nanograms per milliliter and approximately 20-fold higher than those measured by the B9 cells. Since serum C-reactive protein concentrations were much more correlated with serum levels of IL-6/sIL-6 R complexes (r = 0.713, r2 = 0.51, P < 0.0001) than with the serum IL-6 levels measured with the B9 cells (r = 0.435, r2 = 0.19, P = 0.05), the large quantities of serum IL-6 present in IL-6/sIL-6 R complexes appear to be biologically relevant in vivo, at least as far as the induction by IL-6 of acute phase protein production.     

IL-32、MMP-13及IL-1O在类风湿关节炎中的表达及意义研究

目的探讨白细胞介素-32（IL-32）、基质金属蛋白酶-13（MMP-13）、白细胞介素-10（IL-10）在类风湿关节炎（RA）发生、病程发展中的意义。方法采用ELISA法,检测115例RA、76例对照组血清中IL-32、MMP-13及IL-10的水平,并与抗环瓜氨酸肽（CCP）抗体、类风湿因子（RF）、超敏C反应蛋白（hs-CRP）、红细胞沉降率（ESR）等指标进行相关性分析。结果 RA组与对照组比较,IL-32、MMP-13、IL-10水平升高,有统计学意义（P〈0.05）,RA重度活动期组IL-32、MMP-13显著高于稳定期组（P〈0.05）,IL-32、MMP-13水平与抗CCP抗体、ESR、hs-CRP、RF、DAS28、关节肿胀数和关节压痛数呈显著正相关（P〈0.01）,IL-10与ESR、hs-CRP呈正相关（P〈0.05或P〈0.01）。结论 IL-32、MMP-13及IL-10与RA的形成、病程发展有密切关系,可作为观察RA病情活动、疗效判断及预后的新依据。     

Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis

Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.     

Anakinra: an inhibitor of IL-1 for the treatment of rheumatoid arthritis

Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.     

Sex influences on the penetrance of IL-1beta and IL-1RN genotypes for rheumatoid arthritis in the Chinese population

Polymorphism (variable number of tandem repeats) in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and two single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene may be associated with an increased risk of rheumatoid arthritis (RA). This study used sex stratification to investigate a correlation of the three genetic polymorphisms with the risk of RA, on patients with RA and healthy controls. Polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were performed. The frequencies of the IL-1beta+3954 allele and genotype in female patients were significantly different compared with the controls; but in males, only the frequency of the IL-1beta+3954 allele was different. The frequency of the IL-1RN genotype in patients was not statistically different compared with the controls; however, the frequency of IL-1RN allele in female patients was different. The association of the three polymorphisms with the susceptibility to RA appears to be significantly affected by gender.     

类风湿关节炎患者血清 ACCP 抗体、MMP-3、IL-17、IL-18的水平变化及意义

目的：探讨抗环瓜氨酸肽（ACCP）抗体、基质金属蛋白酶-3（MMP-3）、白细胞介素-17（IL-17）、白细胞介素-18（IL-18）在类风湿关节炎（RA）患者血清中的变化和意义。方法酶联免疫吸附试验（ELISA）法检测80例 RA 患者、32例骨关节炎（OA）患者和32例健康对照外周血血清 ACCP 抗体、MMP-3、IL-17、IL-18水平,进行统计分析。结果RA 组 ACCP 抗体、MMP-3、IL-17、IL-18显著高于 OA 组和健康对照组;RA 低、中、高活动组 ACCP 抗体、MMP-3、IL-17、IL-18高于稳定组,RA 组 ACCP 抗体、MMP-3、IL-17、IL-18、疾病活动评价分数（DAS28）、C-反应蛋白（CRP）、红细胞沉降率（ESR）都升高;ACCP 抗体阳性组 MMP-3、IL-17、IL-18、DAS28高于阴性组;RA 组 ACCP 抗体、MMP-3、IL-17、IL-18之间正相关;ACCP 抗体、MMP-3、IL-17、IL18与 RA低、中、高活动组监测指标 CRP、DAS28呈正相关。结论MMP-3、IL-17、IL-18参与 RA 的发生、发展过程;ACCP 抗体、MMP-3、IL-17、IL-18的检测对 RA 患者病情活动的判断和疾病的防治有一定的价值。     

类风湿性关节炎患者滑膜液和外周血中细胞因子的检测和对比分析

目的 探讨细胞因子在类风湿性关节炎(RA)发病中的作用.方法 用酶联免疫吸附试验(ELISA)分析10例RA患者滑膜液和血清中干扰素γ(IFN-γ)、白细胞介素(IL)-10、IL-4与IL-12的含量.结果 RA患者滑膜液中IFN-γ含量很高[(366.7±43.2)pg/ml],而外周血中仅(20.1±3.2)pg/ml.患者滑膜液和外周血中IL-4含量均低于检测下限(＜15 pg/ml).患者滑膜液中IL-12和IL-10含量分别为(419.9±89.2)pg/ml和(187.7±34.5)pg/ml,均高于外周血中的含量[(65.32±34.2)pg/ml和(85.0±12.7)pg/ml].结论 RA患者关节滑膜液中的细胞因子分泌格局为Th1型,且明显高于外周血中含量,提示这些炎性细胞因子增高可能与关节滑膜中的自身反应性T细胞的活化导致的免疫损伤密切相关.