HLA-DR抗原β链的共同表位与类风湿关节炎相关性研究

目的　探讨人类白细胞抗原 (HLA) DR基因编码的共同表位 (SE)与武汉籍汉族类风湿关节炎 (RA)的相关性。方法　采用聚合酶链反应 序列特异性引物技术 (PCR SSP) ,对武汉籍汉族人群 78例RA患者和 12 6例健康者的HLA DRB1 0 1、 0 4基因型进行检测。结果　RA患者中具有编码QKRAA或QRRAA的共同表位阳性率为 43 6 % ,明显高于正常对照组 (15 1% ,P <0 0 1) ;SE阳性的RA患者的关节压痛数、侵蚀性病变以及关节外表现明显高于SE阴性的RA患者(P <0 0 1)。结论　HLA DR基因编码的SE与武汉籍汉族RA易感性及疾病严重性相关 ,共同表位的检测可作为一项病情及预后判断的指标     

Ⅱ型胶原特异性T细胞系与关节炎发病机制的研究

目的　建立Ⅱ型胶原特异性T细胞系 ,研究其对关节炎的诱导作用。方法　通过用弗氏完全佐剂乳化的鸡Ⅱ型胶原 (CCⅡ )皮内免疫注射诱导Wistar大鼠胶原诱导性关节炎 (CIA)。取CIA大鼠肠系膜淋巴细胞在体外用CCⅡ刺激扩增、建立CCⅡ反应性T细胞系。用3 H TdR掺入试验和流式细胞术分别测定其克隆扩增情况和表型格局。观察T细胞系过继转输后Wistar大鼠关节炎的发生情况 ,同时通过肉眼观察和组织化学法鉴定受体大鼠踝关节的病理特征 ;并用酶联免疫吸附试验 (ELISA)测定血清中抗CCⅡ抗体。结果　成功建立T细胞系。通过用荧光素标记抗体作细胞表型分析显示 :所建细胞系 98 2 %为T细胞 ,其中 89 7%为CD4 + T细胞。过继转输试验结果显示 :当注入细胞为 5× 1 0 7时可导致 5 0 %大鼠产生关节炎 ,抗CCⅡ抗体也较对照组明显升高。结论　成功建立T细胞系 ;T细胞系转移关节炎的结果提示 :T细胞在CIA发病机制中具有重要作用。这为RA发病机制的研究和T细胞疫苗的治疗提供了实验依据     

胶原诱导性关节炎小鼠存在血管内皮功能失调——类风湿关节炎加速动脉粥样硬化的新证据

目的类风湿关节炎(RA)患者易患动脉粥样硬化(AS),而RA是否会造成内皮功能障碍,并通过该途径触发或者加速AS是我们的研究重点。方法观察胶原诱导性关节炎(CIA)小鼠及同期对照小鼠的主动脉对于乙酰胆碱及硝普纳诱导的血管舒张率并进行对比,及CIA与对照小鼠血管组织iNOS及eNOS表达水平的检测。结果对照小鼠的主动脉组织中,对于乙酰胆碱的诱导,血管舒张率为88.70±22.90%,CIA显著下降为53.90±18.40%(p<0.01)。对于硝普纳的诱导则未见差异。CIA小鼠血管组织中eNOS表达下调,iNOS表达升高。结论 CIA小鼠存在内皮细胞功能障碍且与关节炎严重程度呈正相关。     

中国汉族类风湿关节炎患者HLA-DR4基因与抗环瓜氨酸肽抗体的相关性研究

目的：探讨中国汉族类风湿关节炎（RA）患者中抗环瓜氨酸肽抗体（ACCP）与人类白细胞抗原（HLA）-DR4基因的相关性。方法：入选RA104例、正常对照122名。ACCP检测采用酶联免疫吸附法（ELISA）,类风湿因子检测采用散色比浊法,HLA-DR4基因采用序列特异性引物-聚合酶链方法（PCR-SSP）检测。结果：RA患者中HLA-DR4基因携带率为34.6%,主要亚型为HLA-DRB1＊0405,正常对照组为17.2%,差异有统计学意义（P=0.01）。RA患者的共同表位（SE）携带率为30.9%,与国内相关研究结果（33.2%,36.8%）相似,但明显低于国外相关研究（78.5%,65.4%,85%,67%）,差异有统计学意义（P〈0.01）。RA患者中ACCP阳性率为76.5%,与国内外报道相符,正常对照组为0,两者差异有统计学意义。SE（＋）患者的ACCP阳性率为84%,SE（-）患者的ACCP阳性率73.2%,两者差异无统计学意义。RA患者中ACCP的滴度与X线分期相关（r=0.233,P〈0.05）。结论：我国汉族RA患者中ACCP与HLA-DR4或SE无明显的相关性。ACCP可能与关节破坏的严重程度相关。     

低氧诱导因子-1α在大鼠胶原诱导性关节炎中的表达及与血管生成的关系

目的制备牛Ⅱ型胶原诱导性大鼠关节炎(CIA)模型,探讨低氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)在类风湿关节炎(RA)组织中的动态表达及其相关性作用。方法 50只SD大鼠,随机分为对照组与模型组。建立CIA模型,动态观察各项关节炎活动指标,于造模21、28、35、42d取踝关节行HE染色及HIF-1α、VEGF免疫组化染色,分析两者在CIA中的相关性及与关节炎活动指标、滑膜病理学评分之间的关系。结果 CIA大鼠关节滑膜层和滑膜下层均表达HIF-1α、VEGF,第21天阳性表达量最高,随病程进展,表达逐渐下降,与滑膜病理学评分、滑膜增生评分及血管生成评分呈显著正相关,与炎症浸润评分无明显相关。结论Ⅱ型胶原可成功诱导大鼠关节炎模型。HIF-1α、VEGF在RA组织中的表达,与炎症严重程度呈明显正相关。HIF-1α可能通过调控一系列下游靶基因,如VEGF等,促进滑膜增生及血管生成,影响RA的发生、发展。     

雷公藤内酯醇对Ⅱ型胶原诱导的关节炎大鼠外周血γδT细胞的影响

目的观察雷公藤内酯醇对Ⅱ型胶原诱导的关节炎（CIA）大鼠外周血γδT细胞比率和凋亡的影响,探讨雷公藤治疗类风湿关节炎（RA）的可能机制.方法以胶原诱导的Wistar大鼠关节炎为动物模型,将造模成功的20只大鼠随机分为模型组和雷公藤内酯醇组.雷公藤内酯醇按4μg/100g体重肌肉注射给药,每3 d 1次,31 d处死动物,运用直接免疫荧光法测定γδT细胞比率,流式细胞仪测定γδT细胞凋亡率.结果与正常对照组比较,CIA模型组外周血中γδT细胞比率明显下降,凋亡率升高,P＜0.01;经雷公藤内酯醇治疗后,γδT细胞比率恢复,接近正常对照组,两组比较差异无统计学意义,P＞0.05.结论减少γδT细胞凋亡,调节CIA大鼠外周血γδT细胞比率,可能是雷公藤内酯醇治疗RA的机制之一.     

维生素D干预对大鼠胶原诱导关节炎模型血管功能的影响

目的 探讨维生素D(VD)对胶原诱导关节炎(CIA)大鼠血管功能的影响.方法 鸡Ⅱ型胶原建立雌性4周龄Wistar大鼠CIA模型,同时设正常对照,模型组及正常组均随机分为VD干预组和空白对照组.每周记录大鼠关节炎评分.造模4及6周时取材.检测大鼠血清25羟维生素D[25(OH)VD]、 肾素、 血管紧张素Ⅱ(ANG-Ⅱ...     

缺氧诱导因子-1α及血管内皮生长因子在Ⅱ型胶原诱导性关节炎模型中的致病作用

目的 探讨低氧诱导因子-1α(HIF-1α)及血管内皮生长因子(VEGF)在Ⅱ型胶原诱导性关节炎(CIA)模型中的致病作用.方法 选用50只SD大鼠(雌雄各半),建立CIA模型,分别于造模第21、28、35、42天取踝关节作HE染色及HIF-1α免疫组化染色,分析其在CIA中与关节炎活动指标,滑膜病理学评分之间的关系.结果 CIA大鼠关节滑膜层和滑膜下层均表达HIF-1α,第21天阳性表达量最高,随病程进展,表达逐渐下降,与滑膜病理学评分、滑膜增生评分及血管生成评分呈显著正相关.结论 HIF-1α在RA致病机制中发挥关键作用,可能是重要的治疗靶点.     

雷公藤多甙对胶原诱导关节炎大鼠的治疗作用及其作用机制

目的探讨雷公藤多甙对类风湿关节炎(rheumatoid arthritis,RA)动物模型,胶原诱导关节炎(collagen induced arthritis,CIA)大鼠血清炎症因子白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumornecrosis factor-α,TNF-α)、血管内皮生长因子(vascuoar endothelial cell growth factor,VEGF)、基质金属蛋白酶(matrix metalloproteinases,MMP)-1、2、9表达的影响,及对成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)ERK信号转导通路的影响,研究雷公藤多甙治疗RA的可能机制。方法采用Ⅱ型胶原建立CIA大鼠模型;观察雷公藤多甙治疗后模型大鼠关节肿胀情况,用免疫组化法观察大鼠关节炎症及滑膜微血管密度;用Western blot法检测CIA大鼠血清IL-1β、TNF-α、VEGF、MMP-1、2、9的表达,并用胶原酶消化法分离培养正常大鼠及CIA大鼠原代FLS;用Western blot法检测不同浓度雷公藤多甙治疗后CIA大鼠FLS中ERK和p-ERK的表达。结果 CIA大鼠造模成功,雷公藤多甙治疗能降低CIA大鼠血清炎症因子及血管新生相关因子表达(P0.05);免疫组化结果显示雷公藤多甙能抑制CIA大鼠关节滑膜血管新生(P0.05);不同浓度雷公藤多甙对FLS中ERK蛋白表达无明显影响,但可降低FLS的p-ERK表达(P0.05)。结论雷公藤多甙对CIA大鼠抗炎及抑制血管新生的作用可能与调节ERK信号转导通路有关。     

蛋白质微阵列对胶原诱导性关节炎大鼠血清细胞因子表达谱的初步研究

目的研究胶原诱导性关节炎(CIA)大鼠不同时期血清蛋白表达谱,寻找与疾病发生和炎症相关的特异表达蛋白,初步探讨类风湿关节炎(RA)的发病机制。方法以含有19个细胞因子的抗体芯片分别检测CIA大鼠发病高峰期和后期及正常大鼠的血清蛋白表达谱,并以酶联免疫吸附试验法(ELISA)测定血清肿瘤坏死因子(TNF)-α表达,验证微阵列检测结果。结果CIA高峰期和后期持续显著上调的细胞因子有10个,高峰期特异高表达细胞因子有1个。微阵列结果没有显示显著下调的细胞因子。结论CIA疾病不同时期细胞因子表达谱不同,筛选出的特异表达蛋白不仅为进一步研究RA的病理机制提供线索,也为疾病的早期诊断提供分子标志。     

Candida septic arthritis in rheumatoid arthritis

We describe a patient with a 10-year history of rheumatoid arthritis who developed septic arthritis of the knee secondary to Candida albicans. Joint sterilization was obtained by debridement and 865 mg. of IV amphotericin B. We review 23 other cases of candidal arthritis in adults with specific reference to disease recognition and treatment.     

Pneumococcal septic arthritis in rheumatoid arthritis.

Septic arthritis is associated with a definite morbidity which may be related to a delay in diagnosis and hence treatment. The cases of three patients with rheumatoid arthritis and chronic chest disease where the joint sepsis was not the predominant feature are presented. The responsible organism was Streptococcus pneumoniae which had spread after recent chest infections. Minimal joint symptoms or general malaise in association with an unexplained rise in erythrocyte sedimentation rate in these circumstances warrant a search for joint sepsis.     

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.     

Corticosteroid prescribing in rheumatoid arthritis and psoriatic arthritis

Corticosteroid usage was assessed in rheumatoid arthritis (RA) and psoriatic arthritis (PA) patients in Italy. A multicentre, observational study was undertaken in 10 Italian rheumatological centres from 1990 to 1992 using a computerised clinical data bank. Nine hundred and seven RA patients and 180 PA patients were studied; 510 (56.2%) RA patients and 44 (24.4%) PA patients were using corticosteroids. The percentage of patients taking corticosteroids ranged from 20.5 to 85.4% for RA patients and from 0 to 55% for PA patients for the different centres. Methylprednisolone was the most prescribed corticosteroid, both in RA patients (63.2%) and in PA patients (65.9%). The average methylprednisolone daily dose was 5.7±3.6 mg in RA patients and 4.5±1.4 mg in PA patients. The data provide evidence that corticosteroids are taken in an unexpectedly high percentage of patients with RA and PA in Italy.     

Infectious arthritis in patients with rheumatoid arthritis.

Eleven cases of infectious arthritis occurring in patients with rheumatoid arthritis are reported. Staphylococcus aureus was the causative organism in eight patients. Streptococcus anginosus and Streptococcus agalactiae in one patient each, and Mycobacterium tuberculosis in two patients. The mean duration of symptoms before diagnosis was 16 days in patients with pyogenic arthritis. The diagnosis of joint infection caused by Mycobacterium tuberculosis was especially delayed (57 days). Four patients died; they were found to have a longer time to diagnosis and two of them had multiple joint infection. Although Staphylococcus aureus is the microorganism most often affecting patients with rheumatoid arthritis, infection caused by Mycobacterium tuberculosis must also be considered in such patients.     

MRI of knee arthritis in rheumatoid arthritis and spondylarthropathies

Summary The knees of fifty-two patients suffering from rheumatoid arthritis (RA), 22 patients with seronegative spondylarthopathies (SA) as well as of 20 healthy volunteers were examined by magnetic resonance imaging (MRI). Osseous erosions (RA 52%-SA 18%; P<0.005), Baker cysts (RA 56%-SA 12%; P<0.005), pannus formation (RA 67%-SA 36%; P<0.05), and cartilage thinning with narrowing of the joint space (RA 46%-SA 18%; P<0.05) proved to be more frequent MRI findings in patients with RA. Additionally, in patients with RA erosions were more extensive. Follow-up MRI examinations of 19 patients revealed an improvment in MRI changes in SA within an average interval of 6 months. No substantial changes were noted in 7 of 13 RA patients. Quantitative and qualitative MRI findings of knee arthritis differ in patients with RA and SA and this was statistically significant. However, as there is considerable overlap of the MRI and radiographic changes in both groups the discriminating diagnostic value in the individual case was limited.Dedicated to Professor Dr. W. Wenz on his 65th birthday     

Cryoglobulins in arthritis

During the years 1984-1986 we saw 22 patients with cryoglobulinemia, 8 of whom had rheumatoid arthritis, 1 psoriasis arthritis, 2 Sj?gren syndrome, 1 progressive systemic sclerosis, 5 different arthralgias, 1 soft tissue rheumatism, 2 vasculitis and arthralgias and 2 purpura-arthralgia-nephritis syndrome. The measurement of cryoglobulins is done only in special cases of diagnostic importance. The prognostic outlook in patients with nephritis is bad. A monoclonal cryoglobulinemia is always suspicious for a lymphoproliferative syndrome.