IL-17及IL-22在大鼠肝移植排斥反应中的表达及意义

目的探讨IL-17及IL-22在大鼠肝移植排斥模型及耐受模型中的表达差异及意义。方法建立大鼠原位肝移植动物模型,分为排斥组和耐受组(各15只),取术后1、3、5、7 d大鼠血浆及肝组织标本,应用ELISA检测其血浆IL-17浓度,应用免疫组化染色、Western blot及荧光定量PCR检测其肝组织内IL-17及IL-22的细胞、蛋白及mRNA的表达情况。结果大鼠原位肝移植模型建立成功,结果显示排斥组IL-17血浆浓度显著高于耐受组;在肝组织中,IL-17及IL-22的淋巴细胞阳性率、蛋白表达水平及mRNA表达水平排斥组显著高于耐受组,且排斥组肝组织中STAT3 mRNA表达水平升高。结论 IL-17及IL-22参与肝移植术后急性排斥反应的发生过程,并推测其通过激活STAT3通路发挥效应。     

IL-22对类风湿关节炎成纤维样滑膜细胞的作用

目的:探究白细胞介素(IL)-22对类风湿关节炎(RA)成纤维样滑膜细胞(FLSs)功能的影响及机制。方法:组织块法培养RA-FLSs。将不同浓度(0、1、10、100μg/L)的重组人源性IL-22(rhIL-22)与RA-FLSs共培养24 h、48 h、72 h,CCK-8法检测细胞活力的改变;利用10μg/L的rhIL-22作用于RA-FLSs 24 h,流式细胞术检测细胞周期改变。rhIL-22和/或信号转导和转录因子3(STAT3)特异性抑制剂STA-21以不同浓度作用RA-FLSs 24h,Western blot法检测Bcl-2和p-STAT3蛋白水平的变化。结果:不同浓度的rhIL-22作用于RA-FLSs 24 h、48 h、72h后,RA-FLSs细胞活力明显增高,均显著高于对照组(P0.05)。rhIL-22刺激RA-FLSs后,S期和G_2/M期细胞明显增多,G_0/G_1期细胞减少。Western blot法检测结果提示rhIL-22可上调RA-FLSs中Bcl-2、p-STAT3的蛋白水平,而STA-21单用或联用rhIL-22均可抑制RA-FLSs中Bcl-2及p-STAT3的表达(P0.05)。结论:IL-22在RA-FLSs细胞活力和周期调节中起重要作用,且STAT3在IL-22促RA-FLSs细胞Bcl-2表达的过程中起关键作用,提示IL-22可能对RA-FLSs凋亡有一定的影响。     

IL-1基因多态性对类风湿关节炎病情及IL-1蛋白表达影响

目的:探讨白细胞介素-1α(IL-1α)和白细胞介素-1β(IL-1β)基因多态性对类风湿关节炎(RA)病情及对IL-1β产生的影响。方法:检测136例RA病人及102例正常人的IL-1等位基因分布,其中72例病人系已明确患病2年内出现关节破坏者,IL-1基因多态性检测采用PCR-RFLP法,同时分析不同类型基因型病人外周血单个核细胞受刺激后分泌IL-1β水平的不同。结果:IL-1α等位基因1、2的频率和携带率在RA组及正常人组无显著差异。IL-1β纯合子等位基因2频率在2年内出现骨侵蚀组明显高于2年内未出现骨侵蚀组,IL-1β纯合子等位基因2携带病人组具有较高的血沉及关节肿胀、压痛指数,从携带IL-1β纯合子等位基因2病人中分离出的外周血单个核细胞经脂多糖刺激后分泌的IL-1β量明显高于其它组病人。结论:RA与IL-1β基因多态显著相关,IL-1β等位基因2促进IL-1β分泌,IL-1β等位基因2的检测可作为预测RA严重性的一个有用指标。     

IL-17在类风湿关节炎患者外周血表达的临床意义

目的：探讨IL-17在类风湿关节炎（ RA）发病中的作用及意义。方法：采用逆转录-聚合酶链反应（ RT-PCR）法检测66例RA患者（活动期34例、缓解期32例）和44例健康对照组外周血单个核细胞（ PBMC）中IL-17 mRNA 的表达水平,采用酶联免疫吸附试验（ ELISA）检测各组血清中IL-17的浓度,用免疫比浊法检测各组血清RF的浓度,分析血清IL-17与RF的相关性。结果：RA患者PBMC中IL-17 mRNA的表达显著高于健康对照组（ P＜0.05）,但活动期与缓解期无明显差异（ P＞0.05）;RA活动期患者血清IL-17水平显著高于RA缓解期患者和健康对照组（ P＜0.05）;且RA患者血清IL-17水平与RF呈正相关。结论：IL-17和RF在RA的发病和病理过程中起重要作用,IL-17可能与RA活动性有关。     

白细胞介素－6与类风湿关节炎

本文概述白细胞介素６（ＩＬ－６）在类风湿关节炎（ＲＡ）发病机理中的作用，综述了血清抗ＩＬ－６与ＲＡ疗效的关系以及抗ＩＬ－６单抗对ＲＡ的治疗作用。     

白细胞介素家族在类风湿关节炎中的表达意义

类风湿关节炎(Rheumatoid arthritis,RA)是一种以慢性破坏性关节病变为特征的全身性自身免疫病。以对称性小关节受累为主,亦有相当比例的患者出现关节外系统受累,以关节滑膜和软骨为主要损伤靶点,并持续处于慢性炎症状态,有反复活动     

血清IL-22与IL-33在类风湿性关节炎合并间质性肺病中的表达及临床意义

探讨类风湿性关节炎合并间质性肺病患者血清IL-22、IL-33水平及临床意义。53例RA患者,分为RA-ILD组和单纯RA组,并与30例健康者对照研究。用Luminex液相芯片技术分别检测血清IL-22、IL-33水平,观察比较各组细胞因子表达情况,并分析相关性。1治疗前RA组及RA-ILD组两组患者年龄、关节肿胀数、压痛数及ESR、CRP、DAS28的比较,差异无统计学意义(均P>0.05)。2治疗前血清IL-22、IL-33在单纯RA组和RA-ILD组的表达均高于健康对照组,差异有统计学意义(均P<0.01),且RA-ILD组较单纯RA组显著增高(均P<0.01)。3RA-ILD患者血清IL-22、IL-33浓度水平与RF、CCP呈正相关(均P<0.05),但与ESR、CRP、DAS28无直线相关性(均P>0.05)。4RA-ILD组患者治疗后血清IL-22、IL-33水平较治疗前明显下降,差异有统计学意义(均P<0.05)。IL-22、IL-33可能参与了RA的发病,同时在RA-ILD发病过程中起重要作用;IL-22、IL-33高表达可作为RA-ILD发病预测及疗效判定的重要参考指标。     

MEKK2在类风湿关节炎患者中的表达及临床意义

研究丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路中有丝分裂原活化蛋白激酶激酶激酶2(mitogen-activated protein kinase kinase kinase 2,MEKK2)分子在类风湿关节炎(rheumatoid arthritis,RA)患者中的表达及临床意义。Western blotting和Real-time PCR分别检测20例RA患者经艾拉莫德治疗前后,外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中MEKK2蛋白和基因的表达水平变化,并与健康对照者比较其表达情况。结果显示:与健康对照者相比,RA患者PBMC中MEKK2的蛋白及基因水平降低,经艾拉莫德治疗后临床症状明显改善,且MEKK2的表达水平有所升高。该研究提示MEKK2的表达对RA发病过程起到重要作用,缓解病情抗风湿药物艾拉莫德有可能影响到MEKK2通路而发挥其临床疗效。     

类风湿关节炎并发OP患者免疫球蛋白、淋巴细胞亚群、IL-27及IL-6水平的研究

目的:探讨免疫球蛋白、淋巴细胞亚群、白细胞介素(interleukin,IL)27和IL-6在类风湿关节炎(rheumatoid arthritis,RA)合并骨质疏松(osteoporosis,OP)患者中的表达及临床意义。方法:选取2018年1月至2020年12月沭阳县中医院收治的268例RA患者为研究对象,测定所...     

类风湿关节炎患者单个核细胞IL-23的表达及意义

目的:通过分析比较类风湿关节炎(Rheumatoid Arthritis,RA)患者血清和外周血单个核细胞(Peripheral bloodmononuclear cell,PBMC)IL-23的表达,探讨其在RA发病过程中的作用,以期为治疗开辟新途径。方法:应用ELISA方法检测RA、骨性关节炎(Osteoarthritis,OA)及正常对照组血清中IL-23和TNFα-蛋白水平,采用RT-PCR法测定各组PBMC中IL-23p19mRNA的表达,并作血清IL-23含量、PBMC IL-23p19mRNA的表达与血清TNFα-水平的相关分析。结果:RA组血清IL-23水平高于正常对照组(P=0.001),其他组间无统计学差异(分别为P=0.122,P=0.127);而各组血清TNFα-的水平均具有统计学差异,RA和OA组均高于对照组(P=0.000,P=0.042),RA组也高于OA组(P=0.013);RA组IL-23p19mRNA的表达高于OA和正常对照组(P=0.000,P=0.000),而OA组与正常对照组差异无统计学意义(P=0.628);血清中IL-23和TNFα-的相关性无统计学差异(r=0.212,P=0.262),而PBMC中IL-23p19mRNA的表达与血清TNFα-呈正相关关系(r=0.392,P=0.032)。结论:IL-23在RA患者PBMC中高表达,在RA的炎性发展过程起到了重要作用。     

类风湿关节炎患者血清IL 37和可溶性PD 1分子的表达水平及临床意义

目的：通过研究类风湿关节炎（RA）患者血清IL 37和可溶性PD 1分子的表达水平,初步探讨其与RA的相关性以及临床意义。方法：收集RA患者及对照组人群的外周血,然后采用酶联免疫吸附法（ELISA）检测30例RA患者（RA标准评分≥6）和30名健康对照组血清中IL-37、sPD-1的表达水平,结合分析两组人群外周血IL-18、IL-6和IL-18BP三种细胞因子的表达,并通过Pearson相关分析其相关性。结果：经ELISA检测发现,RA组患者外周血中IL-37和sPD-1以及其他几种炎症相关细胞因子IL-18、IL-18BP、IL-6的表达水平均高于健康对照组（P＜0.05）;且IL-37与细胞因子IL-18、IL-18BP、IL-6均呈正相关,sPD-1仅与细胞因子IL-6呈正相关,IL-37、sPD-1均与患者病情程度评分呈正相关。结论：IL-37、sPD-1在RA患者中表达水平升高,且与其他炎性细胞因子及疾病严重程度具有相关性,两者在RA的进展中可能发挥着重要的调控作用,为今后RA治疗提供新的依据。     

Anti-MBL autoantibodies in patients with rheumatoid arthritis: prevalence and clinical significance

Occurrence of autoantibodies in patients' sera is the characteristic feature of autoimmune disorders. We assessed the presence of anti-mannose binding lectin (MBL) autoantibodies in the sera of 107 rheumatoid arthritis (RA) patients and 121 control subjects by enzyme immunoassay. Elevated levels of anti-MBL autoantibodies in the sera of RA patients (P<0.0001) was detected for the first time. The ratios of anti-MBL positive in RA patients and controls were respectively 60.7% and 1.65%. Experiments were then designed to understand the functional relevance of these autoantibodies. An inverse correlation of anti-MBL autoantibodies with serum MBL levels (P=0.001) and MBL complex activity (P=0.02) was observed without genetic association between MBL polymorphisms and anti-MBL autoantibody secretion. A significant increase (P=0.038) in the level of anti-MBL autoantibodies was observed in 23 synovial fluid samples in comparison to the serum samples. Moreover, the anti-MBL autoantibodies were found to be more often present in the sera of RA patients (60.75% sensitivity, 98.35% specificity and 0.913 area under the ROC curve) in comparison to the IgM and IgG isotypes of rheumatoid factors (RF). Anti-MBL autoantibodies were still positive in 25.23% RA patients when both the RF isotypes were negative. Also, in RA patients, at all stages of disease activity and joint deformity, anti-MBL autoantibodies were more often present than both the RF isotypes. Therefore, the significant presence of anti-MBL autoantibodies enunciates that anti-MBL autoantibodies might have a diagnostic value; however, more studies are needed to confirm the role of anti-MBL autoantibodies in the diagnosis of rheumatoid arthritis.     

类风湿关节炎患者外周血单个核细胞中TRAIL、c-FLIP 等表达水平及临床意义

目的:分析类风湿关节炎(RA)患者外周血单个核细胞中肿瘤坏死因子相关凋亡诱导配体TRAIL、c-FLIP、Caspase-8等基因表达情况,探讨其在RA中的临床意义,为RA的临床诊治寻找更有效的途径和方法提供实验基础。方法:采用实时荧光定量PCR的方法检测外周血单个核细胞肿瘤坏死因子相关凋亡诱导配体TRAIL、c-FLIP、caspase-8 mRNA 表达水平;采用蛋白免疫印迹法检测PBMC 中TRAIL、c-FLIP、caspase-8 蛋白表达水平。结果:各组RA 患者PBMC 的TRAIL、c-FLIP、Caspase-8 的mRNA 表达水平:中活动组(M)中TRAIL的mRNA为(3.26±0.78),高于健康对照(N)(1.30±0.20,P=0.028)。低活动组(L)和高活动组(H)(1.56±0.37、1.83±0.26),略高于健康对照(N)(P=0.048、0.043);L、M、H 组c-FLIP mRNA相对表达量分别为1.27±0.28,1.32±.34,1.93±0.40,均高于N组1.08±0.12(P 分别为0.035、0.034、0.030),差异有统计学意义;caspase-8 mRNA L、M、H 组中分别为(2.77±0.97)、(4.52±0.85)、(2.13±0.44),均高于N 组(1.04±0.13,P=0.023,0.012,0.032)。RA 患者PBMC 中TRAIL、c-FLIP、caspase-8 蛋白表达:M 组TRAIL 蛋白表达明显高于N 组(P=0.013 ),H 组稍高于N 组(P=0.043),L组与N组无明显统计学差异(P=0.058),M 组明显高于L、H 组(P=0.011,0.021);c=FLIP 蛋白表达中M组明显高于N 组(P<0.01),而L、H 组与N 组无显著差异(P =0.062,0.053);L 组表达与N 组无显著差异(P>0.05),而M、H组caspase-8 蛋白表达明显高于N 组(P=0.003,0.001)。结论:在RA 的不同活动期中,外周血单个核细胞TRAIL、c-FLIP 和Caspase-8 等表达水平总体趋势增加,可为RA 的临床诊治及后续研究提供实验参考。     

Diagnostic value and clinical significance of anti-CCP in patients with advanced rheumatoid arthritis

OBJECTIVES: To investigate the prevalence of anticyclic citrullinated peptide (anti-CCP) in patients with advanced rheumatoid arthritis (RA) and to compare it with those in control subjects. Further, to study the relation between the anti-CCP and the disease activity parameters in these patients. PATIENTS AND METHODS: Seventy-six RA patients who had a mean disease duration of 9.8 years were included. Eighty-three age-matched non-RA volunteers were enrolled as the control group. Disease duration, duration of morning stiffness, swollen and tender joint counts, hand deformity, patient's assessment of pain, anti-CCP, rheumatoid factor (RF) and acute phase proteins were evaluated. The functional disability was also assessed with the Modified Health Assessment Questionnaire (HAQ). RESULTS: Thirty-seven sera (48.7%) in the patient group and one serum (1.2%) in the control group were positive for anti-CCP. RF was positive in 45% of the RA cases and in 5% of controls. Sensitivity and specificity of anti-CCP reactivity for RA were 49.0% and 99.0%, respectively. HAQ score and duration of morning stiffness were found to be significantly associated with anti-CCP positivity. Disease duration, swollen joint count and anti-CCP positivity were the most important variables predicting hand deformity. CONCLUSION: The prevalence, sensitivity and specificity of anti-CCP in patients with advanced RA were found to be similar to those reported in patients with early disease. Anti-CCP was significantly associated with some parameters of both disease activity and severity. Anti-CCP might be a useful parameter in clinical evaluation of patients with advanced RA.     

类风湿关节炎患者血清富含半胱氨酸蛋白61水平及临床意义

目的检测类风湿关节炎(RA)患者的富含半胱氨酸蛋白61(cysteine-rich 61,Cyr61)水平,比较不同病程患者的血清Cyr61水平,对患者血清Cyr61水平与各相关指标进行分析。方法 ELISA方法检测RA与健康对照组的血清Cyr61水平。结果 RA的血清Cyr61水平高于健康对照组(P0.01),早期RA的血清Cyr61水平高于中晚期患者(P0.05),RA的血清Cyr61水平与类风湿因子(RF)水平正相关(r=0.362,P0.05)。结论 Cyr61可能参与RA的发病机制,水平升高可能预示RA预后不佳。     

类风湿关节炎外周血单核细胞亚群CD64表达及意义

目的：探讨CD64在类风湿关节炎（RA）患者外周血单核细胞亚群上的表达及临床意义,以阐明其在RA发生和发展中的作用。方法：应用流式细胞仪检测44例RA患者和22例正常对照者外周血单核细胞亚群的比例及其CD64的表达,比较RA组和正常对照组之间各单核细胞亚群的比例及其表面CD64表达水平,并分析各单核细胞亚群表面CD64表达与实验室检查数据的相关性。两组间比较采用t检验或者非参数检验,两变量之间相关性采用Pearson或Spearman相关分析。结果：(1)RA组中间型单核细胞比例高于对照组,差异有统计学意义(P<0.01);RA组经典型单核细胞比例和非经典型单核细胞比例低于对照组(P<0.05),差异有统计学意义。(2)RA组各单核细胞亚群CD64表达(MFI)显著高于对照组,差异有统计学意义(P<0.05)。(3)RA患者外周血经典型单核细胞和中间型单核细胞CD64表达(MFI)与DAS28呈正相关(r_s=0.308,P=0.044;r_s=0.302,P=0.049)。(4)RA患者各单核细胞亚群CD64表达(MFI)与ESR,CRP呈正相关(r_s=0.410,P=0.008;r_s=0.475,P=0.003;r_s=0.448,P=0.003;r_s=0.473,P=0.004;r_s=0.348,P=0.026;r_s=0.340,P=0.042)。(5)RA患者RF阳性组、ACPA阳性组外周血经典型单核细胞、中间型单核细胞上CD64表达(MFI)明显高于对应的阴性组,差异有统计学意义(P<0.05)。(6)中间型单核细胞CD64高表达组血清细胞因子IL-6水平明显升高,差异有统计学意义(P<0.05)。结论：RA患者外周血单核细胞亚群CD64表达异常,经典型单核细胞和中间型单核细胞CD64表达与炎症水平、自身抗体产生和疾病活动性有明确的相关性。以外,中间型单核细胞CD64的表达与细胞因子相关。     

IgA rheumatoid factor in mucosal fluids and serum of patients with rheumatoid arthritis: immunological aspects and clinical significance.

In order to gain insight into the production and clinical significance of IgA rheumatoid factor (IgA-RF) in mucosal fluids of patients with rheumatoid arthritis (RA), we examined tear fluid, saliva and serum from 80 patients with RA. Significant correlations were found between IgA-RF levels in tear fluid and saliva (P=0.002, r=0.57), saliva and serum (P<0.001, r= 0.79), and serum and tear fluid (P<0.001, r=0.31). No significant correlations were found between total IgA levels in these fluids. Comparison between circulating and mucosal IgA-RF levels after correction for total IgA, revealed that mucosal IgA-RF levels are on average 2.5 times higher than circulating IgA-RF levels. Analysis of IgA-RF specificity showed that lacrimal and salivary IgA-RF reactivity with various IgG subclasses is similar and differs from serum IgA-RF specificity. These results indicate local production of IgA-RF in salivary and lacrimal glands and support the view of a common origin of IgA-RF producing B cells present in mucosal tissues. Mucosal and circulating levels of IgA and IgA-RF were not associated with tests that quantify tear fluid production. This indicates that mucosal and circulating levels of IgA and IgA-RF in patients with RA cannot be regarded as markers for the development of secondary Sjögren's syndrome.