类风湿关节炎患者外周血及滑液NKp44+自然杀伤细胞的表达和临床意义探讨

目的 探讨类风湿关节炎(RA)患者外周血及滑液NKp44+自然杀伤细胞的临床意义.方法 采用流式细胞术检测20例活动期RA患者[疾病活动指数(DAS)28≥2.6]、15例缓解期RA患者(DAS28＜2.6)及20名健康对照者外周血NKp44+自然杀伤细胞比例及10例活动期RA患者滑液NKp44+自然杀伤细胞比例.多重非参数检验比较3组间NKp44+自然杀伤细胞比例差异.采用Spearmar相关分析NKp44+自然杀伤细胞与临床指标[DAS28评分、抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)]的相关性.结果 ①活动期、缓解期RA患者及健康对照者外周血NKp44+自然杀伤细胞比例分别为(1.480±4.750)%、(0.540±0.590)%、(0.000±0.000)%,活动期RA患者外周血NKp44+细胞比例明显高于缓解期和健康对照(x2=46.708,P=0.000).②10例活动期RA患者滑液NKp44+自然杀伤细胞比例为(15.6±11.7)%,明显高于其外周血NKp44+自然杀伤细胞比例(3.6±2.5)%(z=-3.780,P=0.000).③活动期RA患者外周血NKp44+自然杀伤细胞比例与DAS28评分、抗CCP抗体呈正相关(r=0.777,P=0.000;r=0.967,P=0.000),与RF无相关性(r=-0.343,P=0.138).滑液NKp44+自然杀伤细胞比例与DAS28评分、抗CCP抗体呈正相关(r=0.930,P=0.000;r=0.867,P=0.001),与RF无相关性(r=0.564,P=0.09).结论 NKp44+自然杀伤细胞在RA患者外周血及滑液中明显增高,且与DAS28评分、抗CCP抗体呈正相关,提示NKp44+自然杀伤细胞与疾病活动度和病情严重程度相关.

Abstract：

Objective To investigate the clinical significance of NKp44+NK cells in the peripheral blood and synovial fluid of rheumatoid arthritis (RA) patients.Methods The proportions of NKp44+NK cells in the PB of 20 active and 15 remission patients with RA and 20 healthy individuals were detected using flow cytometry.The proportions of NKp44+NK cells in the SF of 10 active patients were detected.Multiple nonparametric test was used to compared the difference of NKp44+NK cells proportions.Clinical data including DAS28,anti-CCP antibody and RF were collected.The relationship between NKp44+NK cells and clinical data was analyzed by Spearman correlation analysis.Results The proportions of NKp44+NK cells in PB of active and remission patients and healthy individuals were (1.480±4.750)%,(0.540±0.590)%,(0.000±0.000)%respectively.The proportion of NKp44+NK cells in PB of active patients was significantly higher than that of remission patients and healthy individuals (x2=46.708,P=0.000).The proportion of NKp44+NK cells in the SF of ten active RA patients was significantly higher than matched PB.There was positive correlation between NKp44+NK cells proportion in PB and SF of active patients and DAS 28 and anti-CCP antibody level.There was no correlation between NKp44+NK cells proportion in PB,SF and RF.Conclusion There is a marked increase in the proportion of NKp44+NK cells in PB and SF of RA patients.Moreover,NKp44+NK cells are positively correlated with DAS28 and anti-CCP antibody,suggesting that NKp44+NK cells may be correlated with disease activity and severity.     

血浆甘露聚糖结合凝集素与类风湿关节炎肾损害的相关性研究

目的 检测类风湿关节炎(RA)相关性肾损害患者甘露聚糖结合凝集素(MBL)的血浆水平,探讨MBL在RA相关肾损害中可能的作用机制.方法 用酶联免疫吸附试验(ELISA)法检测19例RA相关肾损害患者、49例RA不伴肾损害患者及40名健康对照者的血浆MBL水平,并收集RA患者临床资料及相关实验室检查资料进行对比分析.采用x2检验、t检验和Spearman相关分析进行统计学处理.结果 较无肾损害组比,RA相关肾损害组患者肿胀压痛关节数增多[(15±9)和(9±11)个],晨僵时间延长[(2.9±1.3)和(2.3±1.6)h],其他(除肾脏)关节外伴随症状发生率明显升高[(42.1%和16.3%),P＜0.01或P＜0.05];但二组间RA病程、关节畸形的发生率差异无统计学意义(P＞0.05);RA相关肾损害组血小板(PLT)[(376±155)×109/L和(304±121)×109/L]、循环免疫复合物(CIC)[(4.3±3.0)和(2.9±3.3)g/L]、红细胞沉降率(ESR)[(79±46)和(53±31)mm/1 h]、类风湿因子(RF)[(77±42)和(52±49)U/ml]、C反应蛋白(CRP)[(32±28)和(23±18)mg/L]、免疫球蛋白IgG[(11.7±2.6)和(8.4±2.4)g/L]、补体C3[(1.18±0.53)和(0.94±0.21)g/L]高于RA无肾损害组(P＜0.01或P＜0.05),血浆白蛋白(Alb)[(26±13)比(30±9)g/L]低于无肾损害组(P＜0.05);二组RA患者血浆MBL水平均较对照组血浆MBL水平[(3.1±0.5)mg/L]显著下降(P＜0.01),RA相关肾损害组MBL水平[(1.7±1.2)mg/L]较无肾损害组MBL水平[(1.4±1.3)mg/L]升高(P＜0.05);RA相关肾损害组MBL与IgG、C3、CRP、尿蛋白定量(24 h)呈正相关(r分别为0.6,0.6,0.47,0.57;P＜0.05).结论 RA相关肾损害与免疫复合物相关;RA相关肾损害患者血浆MBL水平是升高的,血浆中高水平MBL可能是RA相关肾损害的发病机制之一.

Abstract：

Objective To detect the serum level of mannose binding lectin (MBL) in patients with renal injury induced by rheumatoid arthritis (RA), and to investigate the role of MBL in the pathogenesis of renal injury in RA. Methods ELISA was used to measure the serum MBL level of 19 RA patients with renal injury, 49 RA patients without renal injury and 40 healthy individuals. The clinical features and laboratory markers were compared and analyzed by chi-square test, two independent samples t-test and Spearman's correlation analysis. Results Compared with RA patients without renal injury, the number of tender and swollen joints [(15±9) vs (9±11)], duration of morning stiffness [(2.9±1.3) vs (2.3±1.6) h] and extraarticular manifestations (42.1％ vs 16.3％) in RA patients with renal injury were significantly higher (P＜0.05or P＜0.01). There was no significant difference between the two groups in RA disease duration and jointdeformity(P＞0.05). In patients with renal injury, the level of platelet count [(376±155)×109/L vs (304±121)×109/L], CIC[(4.3±3.0) vs (2.9±3.3) g/L], ESR[(79±46) vs (53±31) mm/1 h], RF[(77±42) vs (52±49)U/ml], CRP[(32±28)vs (23±18)mg/L], IgG[(11.7±2.6)vs (8.4±2.4)g/L], C3[(1.18±0.53)vs (0.94±0.21) g/L] were higher than those in RA patients without renal injury (P＜0.01 or P＜0.05); the level of Alb [(26±13) vs (30±9) g/L] was lower than that in RA patients without renal injury (P＜0.05). The level of serum MBL in the two groups of RA patients was significantly lower than that in the healthy group [(3.1±0.5)mg/L](P＜0.01), and the level of serum MBL in RA patients with renal injury [(1.7±1.2) mg/L] was higher than that in RA patients without renal injury [(1.4±1.3) mg/L](P＜0.05). The level of serum MBL in RA patients with renal injury showed a positive correlation with IgG, C3, CRP and 24 h urine protein level (r=0.6, 0.6, 0.47, 0.57; P＜0.05). Conclusion Renal injury in RA patients is immune complex dependent. The serum level of MBL is higher in patients with renal injury, therefore, high-concentration MBL may be one of a potential causes of renal injury in RA patients.     

血清骨桥蛋白水平与类风湿关节炎活动性的关系及在伴肺间质病变中的意义

Objective To investigate the association between serum level of osteopotin (OPN) and disease activity of rheumatoid arthritis (RA) patients, and explore the importance of OPN in the pathogenesis of interstitial lung disease (ILD) in RA. Methods Sixty-five RA patients and 20 healthy controls were pros-pectively enrolled. RA patients were divided into active group (n=43) and inactive group (n=22), and ILD groups (n=24) and non-ILD group (n=41). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of OPN in patients with RA and healthy controls, and the relationship between OPN and other clinical and laboratory findings were analyzed. Results ① Serum OPN tended to be significantly higher in RA patients (median, 18.0 ng/ml) than in the healthy controls (median, 14.3 ng/ml), P<0.01; ②The serum level of OPN in RA patients showed a significant positive correlation with the course of disease, numbers of tender joints , ESR and CRP, but no positive relationship was found in number of swollen joints; ③ The serum level of OPN was significantly higher in RA-ILD patients (median, 20.0 ng/ml) than that in non-lLD (median, 17.0 ng/ml, P<0.05). And there was remarkable negative correlation between the concentration of serum OPN and the value of PaO2, but no association was found with pulmonary function %VC and %DLCO. ④ Compared with the non-ILD group, the ILD group had more active disease in terms of tender joint counts and swollen joint counts, ESR, CRP (P<0.01) and the serum titer of RF-IgM, (P<0.05). Conclusion OPN plays a role in the pathogenesis of RA and is related to the disease activity. It may serve as an active disease inflammatory marker of RA . OPN may be involved in the pathogenesis of RA related ILD and is associated with the severity of pulmonary damage.     

血清骨桥蛋白水平与类风湿关节炎活动性的关系及在伴肺间质病变中的意义

Objective To investigate the association between serum level of osteopotin (OPN) and disease activity of rheumatoid arthritis (RA) patients, and explore the importance of OPN in the pathogenesis of interstitial lung disease (ILD) in RA. Methods Sixty-five RA patients and 20 healthy controls were pros-pectively enrolled. RA patients were divided into active group (n=43) and inactive group (n=22), and ILD groups (n=24) and non-ILD group (n=41). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of OPN in patients with RA and healthy controls, and the relationship between OPN and other clinical and laboratory findings were analyzed. Results ① Serum OPN tended to be significantly higher in RA patients (median, 18.0 ng/ml) than in the healthy controls (median, 14.3 ng/ml), P<0.01; ②The serum level of OPN in RA patients showed a significant positive correlation with the course of disease, numbers of tender joints , ESR and CRP, but no positive relationship was found in number of swollen joints; ③ The serum level of OPN was significantly higher in RA-ILD patients (median, 20.0 ng/ml) than that in non-lLD (median, 17.0 ng/ml, P<0.05). And there was remarkable negative correlation between the concentration of serum OPN and the value of PaO2, but no association was found with pulmonary function %VC and %DLCO. ④ Compared with the non-ILD group, the ILD group had more active disease in terms of tender joint counts and swollen joint counts, ESR, CRP (P<0.01) and the serum titer of RF-IgM, (P<0.05). Conclusion OPN plays a role in the pathogenesis of RA and is related to the disease activity. It may serve as an active disease inflammatory marker of RA . OPN may be involved in the pathogenesis of RA related ILD and is associated with the severity of pulmonary damage.     

血清骨桥蛋白水平与类风湿关节炎活动性的关系及在伴肺间质病变中的意义

Objective To investigate the association between serum level of osteopotin (OPN) and disease activity of rheumatoid arthritis (RA) patients, and explore the importance of OPN in the pathogenesis of interstitial lung disease (ILD) in RA. Methods Sixty-five RA patients and 20 healthy controls were pros-pectively enrolled. RA patients were divided into active group (n=43) and inactive group (n=22), and ILD groups (n=24) and non-ILD group (n=41). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of OPN in patients with RA and healthy controls, and the relationship between OPN and other clinical and laboratory findings were analyzed. Results ① Serum OPN tended to be significantly higher in RA patients (median, 18.0 ng/ml) than in the healthy controls (median, 14.3 ng/ml), P<0.01; ②The serum level of OPN in RA patients showed a significant positive correlation with the course of disease, numbers of tender joints , ESR and CRP, but no positive relationship was found in number of swollen joints; ③ The serum level of OPN was significantly higher in RA-ILD patients (median, 20.0 ng/ml) than that in non-lLD (median, 17.0 ng/ml, P<0.05). And there was remarkable negative correlation between the concentration of serum OPN and the value of PaO2, but no association was found with pulmonary function %VC and %DLCO. ④ Compared with the non-ILD group, the ILD group had more active disease in terms of tender joint counts and swollen joint counts, ESR, CRP (P<0.01) and the serum titer of RF-IgM, (P<0.05). Conclusion OPN plays a role in the pathogenesis of RA and is related to the disease activity. It may serve as an active disease inflammatory marker of RA . OPN may be involved in the pathogenesis of RA related ILD and is associated with the severity of pulmonary damage.     

血清骨桥蛋白水平与类风湿关节炎活动性的关系及在伴肺间质病变中的意义

Objective To investigate the association between serum level of osteopotin (OPN) and disease activity of rheumatoid arthritis (RA) patients, and explore the importance of OPN in the pathogenesis of interstitial lung disease (ILD) in RA. Methods Sixty-five RA patients and 20 healthy controls were pros-pectively enrolled. RA patients were divided into active group (n=43) and inactive group (n=22), and ILD groups (n=24) and non-ILD group (n=41). Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of OPN in patients with RA and healthy controls, and the relationship between OPN and other clinical and laboratory findings were analyzed. Results ① Serum OPN tended to be significantly higher in RA patients (median, 18.0 ng/ml) than in the healthy controls (median, 14.3 ng/ml), P<0.01; ②The serum level of OPN in RA patients showed a significant positive correlation with the course of disease, numbers of tender joints , ESR and CRP, but no positive relationship was found in number of swollen joints; ③ The serum level of OPN was significantly higher in RA-ILD patients (median, 20.0 ng/ml) than that in non-lLD (median, 17.0 ng/ml, P<0.05). And there was remarkable negative correlation between the concentration of serum OPN and the value of PaO2, but no association was found with pulmonary function %VC and %DLCO. ④ Compared with the non-ILD group, the ILD group had more active disease in terms of tender joint counts and swollen joint counts, ESR, CRP (P<0.01) and the serum titer of RF-IgM, (P<0.05). Conclusion OPN plays a role in the pathogenesis of RA and is related to the disease activity. It may serve as an active disease inflammatory marker of RA . OPN may be involved in the pathogenesis of RA related ILD and is associated with the severity of pulmonary damage.     

mIL—2R,T cell subsets ＆ hepatitis C

AIM: To study the levels of membrane interleukin-2 receptor(mIL-2R ) and T cell subsets in peripheral bloodmononuclear cells (PBMC) from patients with hepatitis Cand their role in the pathogenesis of hepatitis C.METHODS: The levels of mlL-2R and T cells subsets in PBMCWere detected by biotin- streptstividin (BSA) technique beforeand after stimulation with PHA in 203 patients with hepatitis Cwith HCV-RNA( + ), anti-HCV( + ), anti-HCV(-).RESULTS: The total expressive levels of mlL-2R before andafter stimulation with PHA(0.03 ± 0.01, 0.03 ± 0.02, 0.04 ± 0.02, 0.36±0.03), and Tcell subsets in PBMC (0.62±0.06,0.37 ± 0.05, 0.35 ± 0.07) were all lower in patients withhepatitis C than those in normal controls (0.66 ± 0.07, 0.41± 0.06, 0.31 ± 0.05, P ＜ 0.01 ). Among the patients, thelevels of mlL-2R were lower in silence than those in situationof PHA inducting (P＜ 0.01). However, the levels of mlL-2Rwere similar in acute hepatitis C to that in chronic hepatitis C(P＞0.05). The levels of CD3+, CD4+, CD4 +/CD8+ Were lov erand CD8 + was higher in patients with acute and chronichepatitis C with anti-HCV( + ) than those in normal controls (0.62±0.06, 0.37±0.05, 0.35±0.07, 1.18±0.30, 0.61±0.07, 0.37±0.05, 1.39±0.33, 0.31±0.05, P＜0.05-P＜0.01).CONCLUSION: The cellular immunity is obviously changed inpatients with hepatitis C. The levels of mlL-2R end activationof T cells am closely associated with chronicity of hepatitis C.     

类风湿关节炎相关性间质性肺疾病的临床研究

目的 探讨类风湿关节炎相关性间质性肺疾病(rheumatoid arthritis-associated interstitial lung disease,RA-ILD)的临床特点和相关因素.方法 回顾性分析我院2009年住院的135例RA病例.以患者首次出现RA症状为研究起点,以肺高分辨率CT检查发现ILD为研究终点.研究因素包括:性别、年龄、病程、临床表现(包括关节炎、类风湿结节、发热、口干及眼干、雷诺现象、皮疹等)、生化指标、免疫指标、治疗措施等40个变量.经后退法建立Logestic回归分析模型,计算OR值及95%CI.结果 ①135例RA患者中48例发生ILD,占35.6%.其中40例(83.3%)诊断RA平均(85±75)个月后确诊合并ILD;其中29例(60.4%)在检出ILD时无呼吸系统症状.②单因素分析显示RA-ILD组年龄、病程、咳嗽、呼吸困难、Velcro音、类风湿因子(rheumatoid factor,RF)、C3、γ-球蛋白高于RA无ILD组(P＜0.05或P＜0.01).③经后退法建立Logestic回归分析模型,多因素分析显示咳嗽(OR=4.387,95%CI:1.143～16.831,P＜0.05)、Velcro音(OR=6.727,95%CI:2.220～20.378,P ＜0.01)、RF(OR=3.522,95%CI:1.304～9.512,P ＜0.05)是RA-ILD的危险因素.④多因素分析发现的3个危险因素中,RF预测RA-ILD的敏感性最高(79.2%),咳嗽的阳性预测值最高(73.3%).结论 大多数患者RA的诊断先于ILD.部分RA患者的肺问质病变为亚临床型.咳嗽、Velcro音及RF阳性是RA患者发生肺间质病变的相关因素,当患者出现以上症状、体征或实验室检查异常时应该高度警惕发生肺间质病变可能,及时完善相关检查,给予合理治疗,改善预后.

Abstract：

Objective To analyse the clinical feature and risk factors of rheumatoid arthritisassociated interstitial lung disease (RA-ILD). Methods The data of 135 patients with rheumatoid arthritis (RA) hospitalized in the hospital in 2009 were retrospectively analyzed. The study factors included gender, age, disease duration, clinical manifestations (including arthritis, rheumatoid nodules, fever, dry mouth and dry eyes, Raynaud's phenomenon, skin rash), biochemical and immunological indexes, and treatment measures. The date were analyzed with Logistic regression analysis. Results In 135 RA patients, 48 cases (35.6%) had interstitial lung disease (ILD), in which 40 cases (83.3%) were diagnosed combined ILD (85±75) months after the diagnosis of RA, and 29 cases (60.4%) had no respiratory symptoms in the detection of ILD. Univariate analysis showed that age, duration, incidence of cough, dyspnea and Velcro tone, positive rate of rheumatoid factor (RF), C3 and γ-globulin in RA-ILD group were higher than those in RA without ILD group ( P ＜0.05 or P ＜0.01). Multivariate analysis showed that cough (OR =4.387,95%CI :1.143-16.831, P ＜0.05), Velcro tone (OR =6.727,95% CI :2. 220-20. 378, P ＜0.01),and RF ( OR =3. 522,95% CI :1. 304-9. 512, P ＜0.05) were risk factors of RA-ILD. Multivariate analysis identified that the sensitivity of RF was highest (79.2%), and the positive predictive value of cough was highest (73.3%) in three risk factors. Conclusions RA is diagnosed before ILD in most of patients. The interstitial pulmonary damages of some RA patients are subclinical. Cough,Velcro tone and RF are interrelated factors of interstitial pulmonary damages in RA patients. When patients have these symptoms, signs or abnormal laboratory examination, interstitial lung disease should be highly alerted, the relevant checks should be consummated in time, and rational treatment should be carried out to improve prognosis.     

Anxiety and depression in patients with gastroesophageal reflux disease and their effect on quality of life

AIM: To explore the role of psychological factors in gastroesophageal reflux disease(GERD) and their effect on quality of life(Qo L) of GERD patients.METHODS: A total of 279 consecutive patients with typical symptoms and 100 healthy controls were enrolled in the study.All of the participants wereevaluated with the Zung Self-Rating Anxiety Scale(ZSAS), the Zung Self-Rating Depression Scale(ZSDS) and the SF-36 questionnaire.The scores for anxiety, depression and Qo L of the two groups were analyzed.The correlation between psychological factors and Qo L was also analyzed.RESULTS: Compared with healthy controls(34.70 ± 8.00), the scores of ZSAS in the non-erosive reflux disease( N E R D) group(48.27±10.34) and the reflux esophagitis(RE) group(45.38 ± 10.27) were significantly higher(P 0.001).The mean ZSAS score of the NERD group was significantly higher than that of the RE group(P = 0.01).Compared with healthy controls(37.61 ± 8.44), the mean ZSDS scores were significantly higher in the NERD group(49.65 ± 11.09, P 0.001) and the RE group(46.76 ± 11.83, P 0.001).All dimensions of the SF-36 form were negatively correlated with the SAS and SDS scores in patients with NERD and RE(P 0.05).According to the S F- 3 6 form, vitality, mentalhealth and social functioning were significantly correlated with symptoms of depression in patients with NERD and RE.General health was obviously affected by symptoms of depression in patients with NERD(P 0.05).CONCLUSION: Anxiety and depression may play an important role in the occurrence of GERD and especially that of NERD.The Qo L of patients with GERD is reduced by anxiety and depression.     

类风湿关节炎患者血清肽酰基精氨酸脱亚氨酶4水平及其意义

目的 通过检测肽酰基精氨酸脱亚氨酶(PADI)4在类风湿关节炎(RA)患者血清中的水平,探讨其在RA发病机制中的意义.方法 采用ELISA检测100例RA患者、23例其他风湿病患者、24例健康体检者血清中PADI4及抗环瓜氨酸多肽(CCP)抗体水平.结果 (1)RA患者PADI4水平为(620.10±259.82)μg/L,较其他风湿病患者[(404.41±195.38)μg/L]、健康体检者[(522.19±142.40)μg/L]明显升高,差异有统计学意义(F=8.75,P＜0.001).(2)RA患者PADI4-94(rs 2240340)基因型T/T、C/C、T/C PADI4水平分别为(597.43±255.76)μg/L、(674.63±320.67)/μgL、(628.78±274.13)μg/L;PADI4-104(RS 1748033)基因型T/T、Cμg/C、T/C PADI4水平分别为(571.56±138.34)μg/L、(653.41±300.35)μg/L、(640.07±302.82)μg/L.各基因型间PADI4水平差异无统计学意义(P＞0.05).(3)相关性分析:RA组PADI4水平与RA疾病活动评分(DAS28)、ESR呈正相关(r=0.24,P=0.03;r=0.23,P=0.03),而与抗CCP抗体、抗PADI4抗体、C反应蛋白无相关性(r=0.02,P=0.83;r=-0.17,P=0.10;r=0.14,P=0.18).结论 PADI4可能是RA的一个致病性抗原,参与了RA发病,其水平高低反映病情活动程度.

Abstract：

Objective To detect the levels of serum peptidylarginine deiminase (PADI)4 and explore its significance in rheumatoid arthritis ( RA ). Methods The presence of PADI4, anti-PADI4antibodies and anti-cyclic citrullinated peptide (CCP) antibodies levels were examined by enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 100 patients with RA, 23 patients with other rheumatic diseases, and 24 healthy controls. The associations between PADI4 and the disease activity score using 28 joint counts ( DAS28 ) score, anti-CCP antibodies, erythrocyte sedimentation rate ( ESR ),C-reactive protein ( CRP), PADI4-94 ( rs 2240340 ) and PADI-104 ( rs 1748033 ) gene polymorphisms and other indexes were analyzed in RA. Results The levels of PADI4 in RA patients were significantly higher than in other rheumatic diseases and healthy controls ( F = 8. 75, P ＜ 0. 001 ). There was no significantly difference in levels of PADI4 among ADI4-94 ( rs 2240340)/PADI-104 ( rs 1748033 ) genotypes. Conclusions PADI4 is associated with disease activity involved in the RA pathogenesis and may be a RA pathogenic antigen.     

类风湿关节炎患者血清中期因子和白细胞介素-17的表达

目的 探讨中期因子和白细胞介素(IL)-17在类风湿关节炎(RA)患者血清中的表达及其临床意义。方法 应用双抗体夹心酶联免疫吸附试验( ELISA)法检测79例RA、37例骨关节炎及70名健康体检者血清中中期因子、IL-17,同时应用ELISA法检测血清抗环瓜氨酸肽(CCP)抗体,免疫散射比浊法检测C反应蛋白(CRP)、类风湿因子(RF),间接免疫荧光法检测抗角蛋白抗体(AKA),分析中期因子与IL-17、抗CCP抗体、CRP、RF、红细胞沉降率(ESR)、AKA及RA疾病活动度评分(DAS)之间的相关性。多组间比较采用Kruskal-WallisH检验,2组间比较采用Mann-Whitney U检验,相关分析采用非参数Spearman相关分析。结果 RA组血清中期因子水平(327±167) pg/ml显著高于骨关节炎组(209±130)pg/ml和健康对照组(225±109) pg/ml,差异有统计学意义（H=22.01,P＜0.01）,骨关节炎和健康对照组比较差异无统计学意义(D0.05)。RA组IL-17水平(44±15) pg/ml也显著高于骨关节炎组(26±8) pg/ml和健康对照组( 27±8) pg/ml,差异有统计学意义(H=66.89,P＜0.01),骨关节炎组和健康对照组比较差异无统计学意义（P＞0.05）。血清中期因子水平与IL-17、CRP呈正相关（r=0.398,P＜0.01;r=0.285,P＜0.01）,与DAS、RF、ESR、AKA、抗CCP等无相关性。结论 中期因子和IL-17可能在RA疾病的发生、发展中发挥了一定的作用,通过复杂的细胞因子网络相互协同,促进了RA的发生发展。     

炎症及免疫指标对类风湿关节炎患者血脂的影响分析

目的 探讨类风湿关节炎(RA)患者血脂情况以及炎症和免疫状态对血脂的影响.方法 选取2008年至2009年在我院住院的225例RA患者,检测入院第1天的血脂、血沉(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、抗环瓜氨酸肽抗体(抗CCP)、抗角蛋白抗体(AKA)、抗核周因子抗体(APF)、补体(C),分析上述指标对血脂及致动脉粥样硬化指数(AIP)的影响.结果 (1)225例患者中,12.9％的患者总胆固醇(TC)升高,43.6％的患者高密度脂蛋白胆固醇(HDL-C)降低,10.2％的患者低密度脂蛋白胆固醇(LDL-C)升高,14.2％的患者TG升高.(2) TC升高组中C3高于TC正常组(P＜0.05),HDL-C降低组的ESR及CRP高于HDL-C正常组(P＜0.05),LDL-C升高组CRP、C3及C4高于LDL-C正常组(P＜0.05).(3)多因素逐步回归分析显示:C3与TC水平正相关(R2=0.067,P＜0.05),ESR、CRP与HDL-C水平负相关(R2=0.202,P＜0.05),CRP、抗CCP抗体与LDLC正相关(R2=0.129,P＜0.05),ESR、C4与AIP正相关(R2=0.046,P＜0.05).结论 类风湿关节炎患者的系统性炎症及异常免疫反应影响其血脂水平及血脂的致动脉粥样硬化作用.     

The association of anti-CCP antibodies with disease activity in rheumatoid arthritis

Antibodies to citrullinated proteins have been described in patients with rheumatoid arthritis (RA) and these appear to be the most specific markers of the disease. Our objective was to determine the frequency of antibodies to cyclic citrullinated peptides (CCPs) in patients with RA and the association of anti-CCP antibodies with disease activity, radiological erosions and HLA DR genotype. Forty patients with RA and 38 patients with fibromyalgia were included in this study. Serum samples were collected from both patient groups with RA and fibromyalgia. Anti-CCP was measured by the corresponding enzyme-linked immunosorbent assay. Additionally, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score (DAS), visual analog scala (VAS), HLA genotype and radiographic information were determined in patients with RA. The rate of sensitivity and specificity of anti-CCP reactivity for the diagnosis RA were measured (sensitivity 50%, specificity 100%). There is no significant difference between anti-CCP (+) and anti-CCP (-) RA patients for DAS28, VAS, ESR, CRP, disease duration, HLA genotype, and radiological assessment of hand. However, there was a significant difference between anti-CCP (+) and anti-CCP (-) RA patients for RF and the radiological assessment of left and right wrists (respectively, P < 0.05, P = 0.04, P = 0.01). There was no significant correlation between anti-CCP antibody and ESR, CRP, VAS, DAS 28 or radiological assessment. A small but significant correlation was found between RF and anti-CCP antibody (P = 0.02, r = 0.35).     

CD28-T细胞亚群在类风湿关节炎患者外周血和关节液中的表达

目的 探讨CD28-T细胞亚群在类风湿关节炎(RA)患者外周血和关节液中的变化和意义。方法 随机选择RA患者45例,取新鲜抗凝外周血单个核细胞(PBMC),其中15例同时提取关节液单个核细胞( SFMC),以流式细胞技术检测CD28-T细胞数量及其表面可诱导共刺激分子(ICOS)的表达。2 组间比较用独立样本t检验。结果 ①与PBMC相比,RA患者SFMC中CD4+CD28+ ICOS+、CD4+CD28-ICOS+、CD8+ CD28+、CD8+ CD28+ ICOS+T细胞明显升高[(36±19)％与(15±8)％,t=-4.234,P＜0.01;(2.1±2.2)％与(0.6±1.4)％,t=-3.143,P＜0.01;(62±15)％与(47±18)％,t=-2.885,P＜0.01;(9±9)％与(3±3)％,t=-2.131,P＜0.05];CD8+CD28-T细胞明显降低[(38±15)％与(54±18)％,t=2.975,P＜0.01];CD8+ CD28- ICOS+、C1D4+CD28+和CD4+CD28-T细胞无明显变化（P＞0.05）。②同一RA患者SFMC与PBMC相比,CD4+CD28+ICOS+、CD8+ CD28+T细胞明显升高[(38±18)％与(16±10)％,t=-4.065,P＜0.01;(61±16)％与(41±21)％,t=-2.883,P＜0.01];CD8+ CD28-T细胞明显降低[(39±16)％与(59±21)％,t=2.949,P＜0.01]。③缓解期与活动期RA患者相比,PBMC中CD4+CD28-、CD8+ CD28-、CD28-ICOS+T细胞无明显变化（P＞0.05）。结论 RA患者关节液中CD28-T细胞亚群失衡和ICOS分子表达异常,可能是导致RA关节损伤的重要机制。     

高迁移率族蛋白1及Toll样受体4在类风湿关节炎患者血清和外周血单个核细胞中的表达及意义

目的 通过研究高迁移率族蛋白(HMGB)1及Toll样受体(TLR)4在类风湿关节炎(RA)外周血单个核细胞(PBMC)和血清中的表达,探讨HMGB1的作用及其与疾病活动的关系.方法 选取活动期RA患者38例和非活动期RA患者36例及健康对照组26名.采用反转录-聚合酶链反应(RT-PCR)方法检测PBMC中HMGB1 mRNA的表达,酶联免疫吸附试验(ELISA)检测血清中HMGBI蛋白的表达.采用流式细胞术分析PBMC上TLR4的表达.结果 ①活动期RA组PBMC中HMGB1 mRNA相对表达量和血清中HMGB1蛋白水平均高于健康对照组和非活动期RA患者[分别为2.63与0.71.0.93和(10.2±1.2)与(7.5+1.8),(8.3±1.8)ng/ml,P＜0.01.②活动期RA患者CD14+单核细胞和CD3+淋巴细胞上TLR4蛋白相对表达量高于非活动期和健康对照组(P＜0.05或P＜0.01),非活动期患者高于健康对照组(P＜0.05或P＜0.01).③血清中HMGB1蛋白水平与红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、关节压痛数、肿胀数及关节X线分期均呈正相关,亦与TLR4蛋白相对表达量呈正相关.结论 RA患者PBMC具有合成和分泌HMGB1蛋白的功能,并部分通过与TLR4结合激活炎症反应,加重骨质破坏.     

类风湿关节炎患者血清中肿瘤坏死因子样配体1A的测定及临床意义

目的 检测类风湿关节炎(RA)患者血清中肿瘤坏死因子样配体1A(TL1A)的水平,分析 其在RA中的临床意义。方法 收集RA患者血清100例和健康对照者50名,采用双抗体夹心酶联免疫 吸附试验(ELISA)测定血清中TL1A水平,并分析血清TL1A水平与RA各临床和实验室指标的相关性, 计量资料,符合正态分布采用t检验,非正态分布采用Mann-Whitney U检验,计数资料比较采用x2检验, 相关性分析采用Spearman相关分析。结果 RA患者血清TL1A水平为(959±1146) pg/ml,显著高于健 康对照组[(529±154) pg/ml,t=3.683,P＜0.01];并且类风湿因子(RF)、隐性类风湿因子IgG( HRF-IgG)、抗 环瓜氨酸肽(CCP)抗体阳性组TL1A水平[分别为(962±1043)、(833±1104)、(908±1115) pg/ml]均高于阴 性组TLlA水平[分别为(628±343)、(576±134)、(628±4.01) pg/ml],差异有统计学意义(t=3.224,1.317,1.003; P均＜0.05)。另外,TLlA阳性组RA患者的RF、HRF-IgG以及抗CCP抗体阳性率(分别为90％、42％、 85％)均较TL1A阴性组患者（分别为56％、11％、33％）显著升高(x2=-0.372,-2.402,-2.774;P均＜0.05)。结 论TL1A在RA患者血清中表达增高,并与多种自身抗体（包括RF、HRF-IgG和抗CCP抗体）密切相关, 可能是RA预后不良因素之一。     

抗环瓜氨酸肽抗体与类风湿关节炎疾病活动及骨侵蚀关系的研究

目的 探讨类风湿关节炎(RA)患者抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)与疾病活动度、功能状态及骨侵蚀的关系.方法 入选RA患者218例.健康对照41名,ELISA法检测抗CCP抗体,乳胶凝集法检测RF,同时记录RA患者的临床资料.分析抗CCP抗体、RF阳性和阴性患者中疾病活动指数28(DAS28)、健康评估问卷(HAQ)的变化,并探讨其中124例病程>2年的患者抗CCP抗体、RF与骨侵蚀的关系.结果 RA患者中抗CCP抗体阳性率为76%,RF阳性率为71%.DAS28评分在抗CCP抗体、RF阳性患者明显高于阴性患者(P＜0.05);抗CCP抗体浓度与DAS28评分相关(r=0.385,P=0.032);RF滴度与DAS28评分相关(r=0.141,P=0.037);红细胞沉降率(ESR)、C反应蛋白(CRP)及HAQ评分在抗CCP抗体、RF阳性和阴性患者之间的差异无统计学意义(P＞0.05).抗CCP抗体阳性患者更易出现骨侵蚀,与阴性患者相比,差异有统计学意义(P＜0.05).RF阳性和阴性患者之间骨侵蚀的差异无统计学意义.结论 抗CCP抗体、RF与疾病活动度相关,抗CCP抗体阳性患者更易出现骨侵蚀,但RF与骨侵蚀未表现出相关性.     

重组人肿瘤坏死因子受体Ⅱ一Fc融合蛋白联合甲氨蝶呤治疗中重度活动性类风湿关节炎的临床和放射学疗效评估

目的 评价重组人肿瘤坏死因子受体Ⅱ-Fc融合蛋白(TNFRⅡ-Fc,商品名:安佰诺)治疗中重度活动性类风湿关节炎(RA)的临床和影像学疗效.方法 396例RA患者随机分为联合用药组、TNFRⅡ-Fc组和甲氨蝶呤组,疗程均为24周,单因素方差分析美国风湿病学会(ACR)-N、ACR20、ACR50、ACR70、疾病活动指数(DAS )28和治疗前后双手的X线Sharp评分(SHS)等疗效和安全性指标.结果 治疗24周后,ACR-N的年改善率联合组为(12.79±9.24)％,TNFRⅡ-Fc组为(9.56±11.16)％,甲氨蝶呤组为(5.08±11.10)％,联合用药组优于TNFRⅡ-Fc组和甲氨蝶呤组(P＜0.05),TNFRⅡ-Fc组优于甲氨蝶呤组(P＜0.05).ACR20的达标率联合组(80.4％)优于TNFR Ⅱ -Fc组(71.1％)和甲氨蝶呤组(56.7％),差异有统计学意义(P＜0.05或P＜0.01).治疗24周后,联合组ACR50和ACR70的达标率分别为53.6％和27.7％,TNFRⅡ-Fc组为41.2％和15.8％,甲氨蝶呤组为30.8％和7.7％,联合组ACR50达标率优于甲氨蝶呤组(P＜0.01),联合组ACR70达标率优于TNFRⅡ-Fc组和甲氨蝶呤组(P＜0.05或P＜0.01).联合组的DAS28-红细胞沉降率(ESR)改善优于TNFRⅡ-Fc组和甲氨蝶呤组,差异有统计学意义(P＜0.05).双手SHS评分治疗前后差值联合组(-1.7±11.2)较甲氨蝶呤组(2.1±11.5)显著下降(P=0.03).联合组不良反应发生率(40.9％)高于甲氨蝶呤组(28.8％),差异有统计学意义(P＜0.05).结论 本研究显示TNFRⅡ-Fc联合甲氨蝶呤较单独使用TNFRⅡ-Fc或甲氨蝶呤能更有效控制RA的活动性和影像学进展.     

血红蛋白/红细胞分布宽度比值和红细胞分布宽度/血小板比值在类风湿关节炎病情评估中的应用

目的 探讨类风湿关节炎（RA）患者外周血中血红蛋白/红细胞分布宽度比值（Hb/RDW）和红细胞分布宽度/血小板比值（RPR）与疾病活动度及疗效的关系。方法 回顾性分析102例初诊RA患者(RA组)及与之年龄性别相匹配的103例健康体检者（对照组）的临床资料,计算Hb/RDW和RPR水平并进行比较。分析RA患者Hb/RDW和RPR与疾病活动度的相关性及治疗前后的差异。采用受试者工作特征（ROC）曲线探讨Hb/RDW和RPR对RA的辅助诊断作用。结果 与对照组比较,RA组患者Hb/RDW水平明显降低,RPR水平明显升高（P＜0.05）。随着28个关节疾病活动指数（DAS28）升高,RA患者Hb/RDW及RPR呈降低趋势（P＜0.05）。RA组患者的Hb/RDW与ESR、CRP及DAS28均呈负相关（r=-0.381,r=-0.214,r=-0.319,P均＜0.05）,RPR与ESR、CRP及DAS28呈负相关（r=-0.295,r=-0.282,r=-0.278,P均＜0.05）。规律治疗后的RA患者DAS28较治疗前明显降低,Hb/RDW和RPR较治疗前明显升高（P＜0.05）。ROC曲线分析结果显示,Hb/RDW、RPR诊断RA的ROC曲线下面积分别为0.863（P＜0.001）和0.567（P=0.098）。结论 Hb/RDW可以作为RA疾病诊断的参考指标,Hb/RDW和RPR对RA患者疾病活动度及治疗效果的评估具有重要参考价值。