IL-17在类风湿性关节炎中的作用

类风湿性关节炎的发病与多种细胞因子如TNF-α、IL-1、IL-17等有关.IL-17是一种前炎症细胞因子,在活动性类风湿性关节炎患者血清及关节液中表达均增高.IL-17主要由活化的T细胞产生,并能诱导活化T细胞,促进滑膜细胞分泌多种细胞因子,抑制软骨细胞合成基质,增强破骨细胞活性,最终导致骨侵蚀.IL-17能与其他细胞因子相互作用,导致类风湿性关节炎进一步发展.IL-17在类风湿性关节炎进程中起重要的调节作用,因此抗IL-17抗体生物治疗有望成为治疗类风湿性关节炎的新方法.     

IL-22及RANKL在骨性关节炎患者中的表达及调节关系

目的 探究骨性关节炎患者体内细胞核因子-κB受体活化因子配体（Receptor activator of nuclear factor-κB ligand,RANKL）和白介素-22(Interleukin-22,IL-22)的表达差异和调节作用以及在骨性关节炎进程中诱导关节软骨退化的可能机制。方法 采用酶联免疫法检测骨性关节炎患者与正常人血清、关节液中的RANKL和IL-22;番红O-固绿复染观察骨性关节炎患者和正常人关节软骨的组织学改变,免疫组化检测关节软骨中RANKL和IL-22的表达情况;RT-PCR检测骨性关节炎患者和正常人关节软骨组织中RANKL、IL-22和基质金属蛋白酶3(Matrix metalloproteinase-3,MMP-3)等基因的表达水平;蛋白质印迹法检测骨性关节炎患者和正常人关节软骨中RANKL、IL-22和MMP3蛋白的含量。用不同浓度的重组人IL-22(Recombinant human IL-22,rhIL-22)处理体外培养的骨性关节炎患者和正常人的关节软骨细胞,采用RT-PCR检测干预后软骨细胞RANKL和MMP-3基因的表达水平。结果 骨性...     

Th22细胞在人类常见病毒感染中的研究进展

初始CD4 +T淋巴细胞在接受抗原刺激后可分化为不同的辅助性T细胞亚群,并分泌相应的细胞因子发挥生物学效应。Th22细胞是近年被发现的新型CD4 +T淋巴细胞亚群,不同于Th1、Th2和Th17细胞等亚群,Th22细胞分泌白细胞介素(IL)-22、IL-13和肿瘤坏死因子(TNF)-α等因子,不分泌...     

抗TNFα单克隆抗体在II型胶原诱导的关节炎模型中的应用

目的制备胶原诱导的关节炎(collagen induced arthritis,CIA)模型,对AT132进行药效评价。方法制备Ⅱ型胶原诱导的CIA模型,且对新药AT132进行药效评价。HE染色观察膝关节和踝关节的病理变化。ELISA法检测血清中CⅡ、TNFα的表达。流式细胞仪检测小鼠关节滑膜中TNFα、IL-1、IL-6、IL-10的表达。结果 (1)模型组小鼠关节表现为小指关节、足爪、足趾肿胀以及变形,AT132组小鼠关节则表现为轻微的红肿。(2)模型组小鼠膝关节和踝关节病理结果表现为炎性细胞的浸润、滑膜增生、血管翳和破骨细胞的出现,软骨和骨的破坏。AT132组病理结果表现为轻微炎性细胞的浸润和滑膜增生。(3)ELISA法检测结果发现:模型组中CⅡ的表达明显上升,AT132给药组中CⅡ的表达明显下降(P0.01)。(4)流式细胞仪检测结果发现:模型组小鼠关节滑膜中TNFα、IL-1、IL-6、IL-10的表达明显增加,AT132组小鼠关节滑膜中TNFα、IL-1、IL-6、IL-10的表达明显降低(P0.01)。结论 CIA模型造模成功率为100%,AT132能够有效地治疗关节炎小鼠。     

IL-22在急性胰腺炎患者血清中的表达及意义

目的探讨白介素22(Interleukin-22,IL-22)在急性胰腺炎(acute pancreatitis, AP)患者血清中的表达情况及其与AP严重程度的关系;为AP患者临床诊治提供新的思路。方法选取2015年12月至2018年12月安徽医科大学第一附属医院急诊外科及EICU收治的AP患者共70例,按照最新的AP诊疗指南进行分组,采用双抗体夹心酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)测定15例重症急性胰腺炎(severe acute pancreatitis, SAP)、18例中度重症急性胰腺炎(moderately severe acute pancreatitis, MSAP)及37例轻症急性胰腺炎(mild acute pancreatitis, MAP)患者及30例健康对照受试者血清IL-22的水平。结果所有AP患者血清IL-22水平均明显高于对照组,差异有统计学意义(P0.05);IL-22与AP病情严重程度有关,分级程度越高,患者血清IL-22水平越高;SAP组、MSAP组、MAP组及对照组各组间差异有统计学意义(P0.05)。结论 IL-22可能与AP发病发展有关;可能对AP诊治提供辅助参考。     

骨桥蛋白在关节疾病中的表达及其意义

骨桥蛋白(osteopontin,OPN)是一种多功能的细胞外基质蛋白,因最初作为骨组织中一种非胶原基质蛋白被发现而得名[1]。OPN可以广泛参与多种生理和病理过程,包括炎症反应、免疫调节、组织修复、骨的发生发育和重建及肿瘤等[2～5]。同时,多种类型细胞如破骨细胞、软骨细胞、滑膜细胞、内皮细胞及     

缺氧诱导因子1和缺氧诱导因子2在人类着床前胚胎的表达

目的研究缺氧诱导因子1(HIF-1)和缺氧诱导因子2(HIF-2)在人类着床前胚胎各个阶段的表达,探讨这两个氧调节基因在人类早期胚胎发育过程中的作用和意义。方法收集不育症患者捐赠的胚胎,采用巢式逆转录聚合酶链反应(RT-PCR)和实时荧光定量PCR分别定性和定量在5%和20%O2条件下体外培养的人胚胎的HIF-1α和HIF-2αmRNA。采用免疫荧光染色检测人胚胎的HIF-1α和HIF-2α蛋白。结果巢式RT-PCR分别检测了5%和20%O2体外培养的2、4、6、8细胞胚胎和囊胚发现,所有34个胚胎均表达HIF-1α和HIF-2αmRNA。实时荧光定量PCR5%O2培养的人囊胚HIF-1α与18SrRNA的Ct比值为(1.22±0.05);20%O2培养的人囊胚,这一比值是(1.02±0.07);两者比较差异显著(P<0.05)。人胚胎在体外常氧培养条件下的HIF-1αmRNA水平显著高于低氧培养。5%O2培养的人囊胚HIF-2α与18SrRNA的Ct的比值为(1.29±0.04);20%O2培养的人囊胚,这一比值是(1.19±0.11);两者比较无显著差异(P>0.05)。人胚胎在体外低氧培养条件下的HIF-2αmRNA水平与常氧培养无显著差异。5%和20%O2体外培养的2、4、6、8细胞,各个发育阶段人胚胎的HIF-1α和HIF-2α免疫荧光染色均阳性。结论研究结果显示人类着床前胚胎在体外常氧和低氧培养时均表达HIF-1α和HIF-2α。二者可能通过广泛的靶基因系统参与早期胚胎的生长发育和着床过程,在早期胚胎的调控可能不在转录水平,而在转录后水平。     

抗CCP抗体在类风湿性关节炎诊断中的应用进展

目前类风湿关节炎的诊断检查有炎性标志物（包括血沉和C反应蛋白）检测,免疫复合物和补体检测,关节滑液检测以及自身抗体检测。这些指标经常伴随类风湿关节炎的活动而改变,早期诊断主要依靠的是自身抗体检测。抗环瓜氨酸肽（ cyclic citrullinated peptide,CCP）抗体是一种抗角蛋白抗体,在类风湿性关节炎的敏感度和特异度较类风湿因子高。发病一年内,类风湿性关节炎患者大部分血清中可检测到抗CCP抗体的存在,同时抗CCP抗体阳性也可以用来预测严重破坏的类风湿性关节炎。因此,抗CCP抗体对于类风湿性关节炎的早期诊断及预后评估是极有帮助的。本文综述了近年来抗CCP抗体对于诊断类风湿关节炎的应用进展。     

缺氧诱导因子2在肝细胞癌中的表达及临床意义

目的 研究缺氧诱导因子2(HIF-2)在肝癌组织及血清中的表达及其与临床病理因素之间的关系,探讨血清中HIF-2对于肝癌的诊断价值。方法 收集具有完整病例及随访资料的90例患者肝癌组织标本,免疫组织化学法检测肝癌组织中HIF-2的表达,酶联免疫吸附试验ELISA检测患者术前血清中HIF-2的表达,探讨HIF-2的表达与患者临床病理因素的关系。受试者工作曲线(Receiver operating characteristics,ROC)分析比较HIF-2和血清AFP值单独以及联合对肝癌的诊断价值。结果 90例肝癌组织中69例显示出HIF-2阳性表达(76.7%),显著高于癌旁组织(11/90,12.2%),且HIF-2高表达的与血管浸润、肿瘤包膜不完整、TNM分期晚以及病理Edmondson分级高密切相关。肝癌患者术前血清中HIF-2的表达水平明显增高,且其表达与血管浸润、肿瘤包膜、肿瘤TNM分期、病理Edmondson分级以及肝硬化程度相关,ROC曲线分析提示HIF-2联合AFP较HIF-2或AFP拥有更大的曲线下面积。结论 人肝癌组织中HIF-2高表达,其表达与血管浸润、肿瘤包膜、TNM分期以及病理分级相关;联合血清HIF-2和AFP检测可提高肝癌检出率;HIF-2可能作为肝癌早期诊断及预后预测的潜在分子标记物。     

Interleukin newcomers creating new numbers in rheumatology: IL-34 to IL-38

The development of innovative technologies is steadily increasing the body of knowledge on molecules involved in physiological functions. Thus, several interleukins (ILs) have been identified and characterized in the past few years. Here, we detail the structural and functional characteristics of IL-34 to IL-38 with special attention to their involvement in inflammatory joint disease. IL-34 chiefly increases osteoclast activation and proliferation and therefore, it plays a direct role in bone destruction as seen in rheumatoid arthritis (RA). Regulatory T-cells (Tregs) express IL-35, which therefore exerts anti-inflammatory effects by restoring Treg suppressive capabilities and by inhibiting the Th17 pathway. IL-37 has anti-inflammatory effects mediated by a negative feedback loop that decreases the release of pro-inflammatory cytokines. IL-36 belongs to the IL-1 family and has three different forms. Although this cytokine has been chiefly studied in psoriasis and psoriatic arthritis, it also exerts pro-inflammatory effects in RA. The specific IL-36 antagonist, IL-36Ra binds to the IL-36 receptor, thereby, preventing signal transduction. Finally, IL-38 is a recently identified cytokine whose effect may resemble that of IL-36Ra as it binds to the IL-36 receptor and inhibits its effects, particularly the Th17-response. Although the exact roles for these cytokines awaits elucidation, the current improvements in our knowledge of the mechanisms that regulate chronic inflammatory conditions, such as RA may lead to the identification of new treatment targets.     

IL-15在类风湿关节炎中的作用研究

目的通过检测血浆IL-15水平,探讨其在类风湿关节炎(RA)发病机制中的作用及与RA患者病情活动程度的相关性,并比较RA和骨关节炎(OA)患者血浆IL-15水平。方法RA患者68例,均符合美国风湿病学会(ARA)制定的RA分类标准;膝OA患者32例,均符合ARA制定的原发性膝骨关节炎分类标准;正常对照组30例,来自本院健康体检者。采用竞争性酶联免疫吸附试验(ELISA)分别测定血浆中IL-15水平。结果RA患者血浆IL-15水平显著高于健康对照组(P<0.01)和OA组(P<0.01),RA活动组血浆IL-15水平显著高于RA缓解组,且与疾病活动性相关。不同X线分期的RA患者血浆IL-15水平之差异有统计学意义(Ⅰ期与Ⅱ期、Ⅱ期与Ⅲ期、Ⅲ期与Ⅳ期分别为P<0.01、P<0.01、P<0.05)。结论IL-15在RA发病过程中起一定作用,可作为RA病情活动的监测指标之一。IL-15也参与了RA的骨破坏,可作为RA与OA鉴别诊断的推荐指标之一。     

Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts)

ObjectivesTo assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.MethodsThis work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.ResultsThe AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14–3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68–6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94–18.69], p = 0.002) on the risk of erosions in ACPA+ patients.ConclusionA haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.     

骨质疏松与类风湿关节炎

类风湿关节炎和骨质疏松在我国都属于常见病和多发病,而二者之间又有着非常重要的联系。但是目前临床上还没有一个广泛应用的药物可以同时对两者都产生很好的治疗效果。为了进一步了解骨质疏松和类风湿关节炎的关系,将来能够找到更好的治疗药物,笔者从流行病学、发病机制以及治疗方法等方面分别进行了论述。     

A multi-parameter response prediction model for rituximab in rheumatoid arthritis

Objectives

To validate the IFN response gene (IRG) set for the prediction of non-response to rituximab in rheumatoid arthritis (RA) and assess the predictive performance upon combination of this gene set with clinical parameters.

Low-power laser therapy in rheumatoid arthritis

Thirty-five patients suffering from rheumatoid arthritis were allocated at random to treatment with either a low-power laser (3.58 J cm^–2, continuous wave 820 nm) or a placebo in a 4-week, double-blind study. Eight finger joints (2nd–5th metacarpo- and proximal interphalangeal joints) of the most affected hand were treated. In the laser group the grip strength and finger flexibility improved, the swelling of the joints declined, the morning stiffness and pain decreased. The sedimentation rate and the number of leukocytes showed a fall with a significant trend. In the placebo group there were no changes in these parameters except for the registration of pain, where a significant, less than with the laser, effect was observed. Thus, low-power laser therapy, at the chosen wavelength and energy dose, appears to be effective against the classical complaints from rheumatoid arthritis.     

基质金属蛋白酶3在类风湿关节炎中的表达及调控

类风湿关节炎是一个病因未明的、以慢性关节滑膜炎症和进展性关节破坏为主要表现的自身免疫性疾病。其早期关节改变是滑膜细胞增生和新生血管形成,最终导致局灶性、关节旁和系统性骨丢失。基质金属蛋白酶是一种能降解细胞外所有基质的锌蛋白酶,研究发现,类风湿关节炎患者血清基质金属蛋白酶3(MMP-3)对细胞外间质的降解和关节骨及软骨的破坏均发挥着重要作用,是系统性的炎症标志物,可作为类风湿关节炎特别是早期患者滑膜损害和预后的指标,同时也是评价抗风湿药物治疗疗效的重要指标。因此,本文主要从MMP-3的结构、功能及表达调控方面作一综述,以期对类风湿关节炎的发病机理作进一步的探讨。     

Clinical characteristics and outcomes in polyarticular septic arthritis

Objectives

Septic polyarthritis is rarer than septic monoarthritis, but associated with higher mortality. Septic polyarthritis may be difficult to distinguish clinically from noninfectious inflammatory arthritis. We describe one of the largest samples of septic polyarthritis with the aim of distinguishing septic monoarthritis from polyarthritis.