类风湿关节炎患者血清中IL-27、炎症指标和疾病活动度的相关性分析

目的探讨类风湿关节患者血清中IL-27、炎症指标和疾病活动度的关系。方法选择97例类风湿关节炎患者和43例健康对照者,通过免疫比浊法检测血清中的C反应蛋白、类风湿因子;ELISA试剂盒检测血清IL-27和抗环瓜氨酸抗体(CCP)水平;魏氏法测定红细胞沉降率;用Mann-Whitney秩和检验比较RA患者和健康对照者血清中IL-27的差别,并对服药前后的患者体内的IL-27水平进行比较;对各指标间的关系采取Spearman相关性分析。结果 RA患者的IL-27血清学水平显著高于所有正常对照(P0.001),并且IL-27的水平与RA的疾病活动度相关(r=0.299,P=0.039),经过免疫抑制剂治疗后RA患者血清IL-27水平显著下降(P0.001)。结论 IL-27与CCP、ESR、CRP等指标相关性不大,但与疾病的活动度(DS28)密切相关,因此,IL-27参与了RA的疾病过程,将是一个较好的指示RA疾病活动度的早期指标。     

火把花根片有效减轻RA患者临床症状与其抑制炎症反应相关

目的观察火把花根片治疗类风湿关节炎(rheumatoid arthritis,RA)的临床疗效及相关机制。方法 40例RA患者进行口服火把花根片治疗12周,治疗前后采集静脉血5ml,酶联免疫吸附测定(ELISA)抗环瓜氨酸抗体(ACPA),乳胶法检测C-反应蛋白(CRP)、免疫比浊法检测类风湿因子(RF)、魏氏法检测红细胞沉降率(ESR),同时监测疾病活动度:包括疼痛视觉模拟评分(VAS)、基于红细胞沉降率的28处关节疾病活动度评分(DAS28-ESR),并记录治疗前后的血常规、肝、肾功能及不良发应。结果治疗后RA患者CRP、ESR水平明显下降(P=0.0081、P=0.0318),VAS、DAS28-ESR评分也显著下降(P0.0001、P0.0001),但RF、ACPA改变不明显,差异无统计学意义(P0.05);治疗前后血常规、肝、肾功能比较无明显变化(P0.05)。结论火把花根片有效减轻RA患者临床症状与其抑制炎症反应相关,并对肝肾功能及血液系统无明显副作用。     

类风湿性关节炎患者血清中结缔组织生长因子水平分析

目的研究类风湿性关节炎(RA)患者血清中结缔组织生长因子(CTGF)的水平,分析其临床意义。方法采用ELISA检测40例RA患者和20例正常对照者血清中CTGF水平,并分析与RA患者各临床和实验室指标相关性。结果 RA组患者血清的CTGF水平高于健康对照组。在DAS28≥5.1的RA高疾病活动度组患者血清CTGF水平高于DAS285.1的中低疾病活动度组患者。RA的血清CTGF水平与类风湿因子水平呈正相关,与血沉、C反应蛋白(CRP)、DAS28评分无明显相关性。结论 RA患者尤其高疾病活动度组RA患者血清CTGF水平明显升高,与RF水平呈正相关。     

昆仙胶囊治疗类风湿关节炎的临床研究

目的比较昆仙胶囊(KUN XIAN)与来氟米特(Leflunomide, LEF)单药治疗类风湿关节炎(rheumatiod arthritis, RA)患者的临床疗效。方法选取RA患者80例,随机分为KUAN XIAN组(50例)和LEF组(30例)。分别于第0、4、12周比较两组的临床指标,包括红细胞沉降率(erythrocyte sedimentation rate,ESR)、C反应蛋白(C-reactive protein, CRP)、类风湿因子(rheumatoid factor, RF)、抗环瓜氨酸抗体(anti-cyclic citrullinated peptide antibody, CCP);同时监测疾病活动度,包括28个关节疾病活动度评分(disease activityscore28,DAS28)、疼痛视觉模拟评分(visualanaloguescore,VAS)及健康评估问卷(healthassessmentquestionnaire, HAQ)。结果 KUN XIAN组在治疗4周后,ESR、CRP、 DAS28、VAS及HAQ评分均较治疗前明显下降,而LEF组则在治疗12周后有显著下降。且在治疗12周后KUN XIAN组ESR、CRP及DAS28水平均明显低于LEF组,而两组的VAS及HAQ评分无显著差异。在治疗12周时,两组的RF及CCP水平均较治疗前显著下降,但两组之间无差异。结论 KUN XIAN治疗RA疗效优于LEF,且起效快。     

类风湿性关节炎患者外周血单个核细胞微管相关蛋白1轻链3(LC3)表达增强且与病情相关

目的检测类风湿性关节炎(RA)患者外周血单个核细胞(PBMC)中自噬标志性分子微管相关蛋白1轻链3(LC3)的mRNA及蛋白表达,探讨其与RA发病的关系。方法募集22例RA患者,同期纳入性别、年龄匹配的16例健康体检者为正常对照组。采用密度梯度离心法分离PBMC;采用实时荧光定量PCR检测PBMC中LC3在mRNA水平, Western blot法检测PBMC中LC3蛋白水平,采用免疫荧光细胞化学染色检测PBMC中LC3蛋白表达;采用Pearson方法分析LC3表达与RA患者临床指标的相关性。结果与正常对照组相比, RA患者组PBMC中LC3 mRNA和蛋白水平明显增加, PBMC中LC3表达明显增强, RA患者PBMC中LC3 mRNA水平与血沉(ESR)、 28关节疾病活动度评分(DAS28)、 C反应蛋白(CRP)、类风湿因子(RF)均呈明显正相关(r依次为0.7480、 0.5016、 0.6518、 0.7232)。结论 RA患者LC3表达上调,且与ESR、 DAS28、 CRP、 RF相关。     

类风湿性关节炎患者血浆腺苷酸活化蛋白激酶(AMPK)水平升高并与疾病活动度呈正相关

目的探索血浆腺苷酸活化的蛋白激酶α1(AMPKα1)与磷酸化的腺苷酸活化的蛋白激酶(p-AMPK)水平与类风湿性关节炎(RA)炎症活动度的相关性。方法募集健康人(HC)15例、骨关节炎(OA)患者17例、 RA患者61例[依据28个关节疾病活动度-血沉(DAS28-ESR)评分,其中22例为高疾病活动,20例为中度疾病活动,19例为低疾病活动]。测定患者ESR、 C-反应蛋白(CRP)水平; ELISA检测血浆AMPKα1与磷酸化的AMPK(p-AMPK)水平以及白细胞介素17(IL-17)、肿瘤坏死因子α(TNF-α)水平。Pearson检验比较AMPKα1与p-AMPK水平与DAS28、炎症相关性指标及炎症因子的相关性。结果与HC人群相比,OA患者及不同疾病活动度的RA患者血浆AMPKα1与p-AMPK水平在一定程度上增加; p-AMPK水平与DAS28呈中等强度的正相关性(r=0.27,95%CI:0.01～0.49),AMPKα1显示出与TNF-α水平中等强度的正相关性(r=0.46,95%CI:0.24～0.64)。结论 p-AMPK水平在RA患者血浆中可能反应性增高,并与临床病情活动度、炎症指标显示出正相关性。     

正五聚体蛋白3、IL-6和CRP水平与RA疾病活动度的相关性

为探讨正五聚体蛋白3(pentraxin 3, PTX-3)、IL-6和CRP水平与RA疾病活动度的相关性,以90例RA患者为研究组,其中疾病低度活动者30例(33.3%),中度活动者44例(48.9%),高度活动者16例(17.8%)。同期纳入60例健康者为对照组,分析研究组与对照组血清中PTX-3、IL-6及CRP水平的差异。结果显示,研究组中PTX-3和CRP水平远高于对照组(P0.001)。随着RA病情的发展,疾病活动指数DAS 28评分越高的患者,IL-6和CRP水平越高(均P0.001),同时,ESR在高度活动组中水平更高(P0.001)。此外,低、中、高度活动组中PTX-3水平均远高于对照组(均P0.001)。CRP、IL-6和ESR水平与DAS 28评分呈低度正相关(r=0.654,P0.001;r=0.555,P0.001;r=0.557,P0.001),IL-6与ESR水平也呈正相关(r=0.489,P0.001)。由此PTX-3、IL-6、CRP可作为RA的生物标志物,几项指标的联合监测可有效反映病情发展状况,为临床治疗提供实验依据。     

滤泡调节性T细胞减少与类风湿性关节炎发生和发展相关

目的探讨滤泡调节性T(Tfr)细胞在类风湿性关节炎(RA)发病中的可能机制。方法采用流式细胞术检测20例RA患者及20例健康体检者外周血中CD4~+CXCR5~+FOXP3~+ICOS~+ Tfr细胞的百分比并分析Tfr细胞比例与RA临床实验室检测指标的相关性;ELISA检测患者血清中白细胞介素10(IL-10)、 IL-12、 IL-2、转化生长因子β(TGF-β)、 CXC趋化因子配体13(CXCL13)的水平;实时定量PCR检测外周血单个核细胞(PBMC)的B细胞淋巴瘤因子6(Bcl6)、 B淋巴细胞诱导成熟蛋白1(Blimp-1)的mRNA表达;免疫组织化学法检测RA患者关节滑膜Bcl6、 CXCL13的表达。结果与健康对照组相比,RA患者外周血Tfr细胞比例显著下降;Tfr细胞百分比与C反应蛋白(CRP)、类风湿因子(RF)、血沉(ESR)、 28关节疾病活动度评分(DAS28)水平呈负相关;RA患者血清中IL-12、 CXCL13表达水平显著升高,IL-2、 IL-10、 TGF-β表达水平显著降低;RA患者PBMC的Bcl6 mRNA水平显著增高,而Blimp-1 mRNA的表达显著降低;RA患者的关节滑膜中观察到Bcl6、 CXCL13显著高表达。结论外周血Tfr细胞比例减少可能与RA的发生发展有关。     

类风湿关节炎患者血清可溶性髓样细胞触发受体-1、白介素-17水平分析

目的检测类风湿关节炎血清可溶性髓样细胞触发受体1(soluble triggering receptors expressed on myeloid cells-1,sTREM-1)与白介素-17(interleukin-17,IL-17)的血清水平,探讨两者在类风湿关节炎(rheumatoid arthritis,RA)中的变化,分析两者在发病过程中可能作用及临床应用前景。方法应用双抗体夹心酶联免疫吸附试验(ELISA)检测114例RA患者(稳定期组46例、活动期组68例),39例其他风湿免疫系统疾病患者(非RA组)及32例正常对照者血清中可溶性髓样细胞触发受体1(sTREM-1)与白介素-17(IL-17)的水平,同时检测类风湿因子(RHF)、C反应蛋白(CRP)、抗环瓜氨酸肽抗体(anti-CCP)及血沉(ESR)。结果RA组sTREM-1、IL-17较正常对照组高(P=0.03,0.02),且sTREM-1在活动期RA明显高于稳定期RA(P=0.02);RA组血清中sTREM-1与IL-17(r=0.97,P=0.001)、CRP(r=0.255,P=0.006)及ESR(r=0.442,P=0.001)变化呈正相关;未发现sTREM-1、IL-17血清水平变化与病程相关(P=0.64,0.50);两项血清学指标在RA组及非RA组间无统计学意义(P=0.39,0.09)。结论 RA患者sTREM-1水平与反应疾病活动的指标如CRP、ESR水平之间具有良好的相关性;sTREM-1参与RA的发病及疾病活动过程,有可能成为类风湿性关节炎活动性新指标;血清sTREM-1与IL-17水平变化呈正相关,两者在RA发病及病情活动中可能起协同作用。     

类风湿性关节炎患者外周血Th17细胞/调节性T细胞比例增加并与疾病活动相关

目的通过检测类风湿性关节炎(RA)患者外周血Th17细胞、调节性T细胞(Treg)的相对数量,探讨其在RA发病机制中的作用及其临床意义。方法选取符合入组标准的RA患者60例及健康体检者15例,采用流式细胞术检测Th17细胞/Treg占外周血CD4+细胞百分比,比较其在RA患者与健康体检者间的差异,分析其表达与肿胀关节数、压痛关节数、28个关节疾病活动度评分(DAS28)、疼痛视觉模拟评分(VAS)、红细胞沉降率(ESR)、C反应蛋白(CRP)的关系。结果与健康对照组比较,RA组患者外周血Th17细胞数量明显增加、Treg数量明显减少。RA患者外周血中Th17细胞数量与肿胀关节数、压痛关节数、DAS28分值及CRP呈正相关;RA患者外周血中Treg的数量与肿胀关节数、压痛关节数、疼痛VAS、DAS28分值、ESR及CRP等病情活动指标无明显相关性。结论 RA患者外周血Th17细胞增加,Treg减少,以Th17占优势,Th17细胞数量增加与RA病情活动有关。     

Positive association between serum thymic stromal lymphopoietin and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis

Thymic stromal lymphopoietin (TSLP) has been suggested recently to play an important role in the pathophysiology of rheumatoid arthritis (RA). However, there is little information on serum TSLP concentrations in RA and its clinical significance. The present study investigated whether serum TSLP concentrations were affected in patients with RA. Using an enzyme-linked immunosorbent assay (ELISA), we measured TSLP concentrations in the serum obtained from 100 patients with RA, 60 patients with osteoarthritis (OA) and 34 healthy volunteers. We also investigated the correlation between serum TSLP concentrations and clinical parameters of disease activity in RA [disease activity score using 28 joint counts (DAS28)-C-reactive protein (CRP), DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI]), patient’s/-physician’s Visual Analogue Scale (VAS), swollen joints count, tender joints count, CRP, ESR and matrix metalloproteinase-3 (MMP-3) concentrations]. In addition, we investigated the correlation between serum TSLP concentrations and anti-citrullinated peptide antibody (ACPA) and serum tumour necrosis factor (TNF)-α. Serum TSLP levels in patients with RA were significantly higher than those in patients with OA and in healthy volunteers. Interestingly, serum TSLP concentrations were correlated significantly with ACPA titres, but not with other clinical parameters. There was a significant increase in serum TSLP concentrations in patients with RA, which was correlated positively with serum ACPA titres. These findings suggest that in patients with RA, TSLP may play a role in ACPA production by B cells.     

Associations between acute phase reactant levels and disease activity score (DAS28) in patients with rheumatoid arthritis

Serum levels of acute phase reactants (APR) were measured in patients with rheumatoid arthritis (RA) and the correlations of these parameters with the disease activity score (DAS28) were investigated. The study included 47 patients with RA and 50 healthy controls. Laboratory tests included erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), haptoglobin (Hp), ferritin, and plasma fibrinogen. Disease activity was assessed using the DAS28 score. The means (+/- SD) of ESR, CRP, Hp, ferritin, and fibrinogen levels were respectively 36.0 +/- 23.5 mm/hr, 2.4 +/- 1.9 mg/dl, 121.3 +/- 34.2 mg/dl, 67.7 +/- 36.2 ng/ml, and 371.2 +/- 96.0 mg/dl in the patients with RA, vs 16.4 +/- 11.3 mm/hr, 0.4 +/- 0.3 mg/dl, 104.0 +/- 35.3 mg/dl, 50.9 +/- 23 ng/ml, and 332.2 +/- 58.5 mg/dl in the controls. All of the APR levels were significantly higher in patients vs controls (p < 0.001 for ESR and CRP; p < 0.05 for Hp, ferritin, and fibrinogen). There were significant correlations between serum APR levels and disease activity based on DAS28 score in RA patients (for CRP, r = 0.650, p <0.01; for Hp, r = 0.331, p < 0.05; for ferritin, r = 0.299, p < 0.05; for fibrinogen, r = 0.373, p < 0.01). This study indicates that serum CRP, among the various ARP tests, is the most useful biochemical marker for evaluating the disease activity of patients with RA.     

Serum Levels of Calreticulin in Correlation with Disease Activity in Patients with Rheumatoid Arthritis

Objective

The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA).

Methods

Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative.

Results

Serum CRT levels in RA patients (4.817?±?2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574?±?0.942 ng/ml), SLE (4.013?±?1.536 ng/ml), other autoimmune diseases (3.882?±?0.837 ng/ml) and HC (3.726?±?0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P?<?0.01).

Conclusion

Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.     

Levels of antioxidant proteins and soluble intercellular adhesion molecule-1 in serum of patients with rheumatoid arthritis

Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), ceruloplasmin (Cp), and transferrin (Tf) were measured in patients with rheumatoid arthritis (RA) and the correlations of these parameters with disease activity were investigated. Serum sICAM- 1 levels were determined by a sandwich enzyme-linked immunosorbant assay (ELISA) in serums from 42 patients with RA and 30 healthy controls. Erythrocyte sedimentation rate (ESR) was determined by the Westergren method and C-reactive protein (CRP), Cp, and Tf by nephelometric methods. Disease activity was assessed by standard criteria. Serum Tf levels were significantly diminished and serum levels of sICAM-1 and Cp were significantly increased in patients with RA, compared to healthy controls. Serum sICAM-1 levels showed negative correlation with serum Tf levels (r = -0.47, p < 0.01), and positive correlation with serum Cp levels (r = 0.49, p < 0.001). There was weak positive correlation between sICAM-1 levels and the Ritche articular index (RAI) scores (r = 0.32, p <0.05) and serum CRP levels (r = 0.44, p <0.01), but no significant correlations of sICAM-1 levels with ESR, patient's age, or duration of disease. There were no significant correlations between values of serum CRP, RAI score, or ESR with serum CP or Tf levels. This study indicates that serum sICAM-1, together with other parameters, is a useful and novel marker for evaluating the disease status and activity of patients with RA.     

Serum amyloid a circulating levels and disease activity in patients with juvenile idiopathic arthritis

The aim of our study was to evaluate the association between circulating levels of serum amyloid A protein (SAA) and disease activity in patients with juvenile idiopathic arthritis (JIA). Our study group included 41 JIA patients (9 male, 32 female), classified according to the International League of Associations for Rheumatology (ILAR) criteria (5); 16 had polyarticular onset disease and 25 had oligoarticular onset disease. Among 25 patients with oligoarticular disease, three had extended oligoarthritis. Serum amyloid A (SAA), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured in both patients and 26 healthy controls. SAA levels were higher in JIA patients versus healthy controls (p<0.001). Significant positive correlations were found between SAA and the presence of active joints (rho=0.363, p<0.05), the number of active joints (rho=0.418, p<0.05), ESR (R=0.702, p<0.05) and CRP (R=0.827, p<0.05). No significant correlations between ESR and the presence of active joints (rho=0.221, p=0.225) or between ESR and the number of active joints (rho=0.118, p=0.520) were demonstrated in JIA patients. No significant correlations were obtained between CRP and the presence of active joints (rho=0.034, p=0.855) or between CRP and the number of active joints (rho=0.033, p=0.859). We discovered a significant increase in SAA levels in JIA patients, compared to controls, and a strong positive correlation between SAA level and JIA disease activity. We also discerned SAA to be a more sensitive laboratory marker than ESR and CRP for evaluating the presence and number of active joints. We suggest that SAA can be used as an additional indicator of disease activity in JIA.     

The diagnostic utility of anti-cyclic citrullinated peptide antibodies, matrix metalloproteinase-3, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein in patients with erosive and non-erosive rheumatoid arthritis

OBJECTIVE: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3), anticyclic citrullinated peptide (CCP) antibodies, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) in patients with erosive and non-erosive rheumatoid arthritis (RA). METHODS: We assembled a training set, consisting of 60 patients with RA, all fulfilling the revised criteria of the American College of Rheumatology. A commercial enzyme linked immunosorbent assay (ELISA) was used both to test for anti-CCP antibodies (second generation ELISA kit) and MMP; RF were detected by latex-enhanced immunonephelometric assay. CRP was measured by latex turbidimetric immunoassay. RESULTS: The levels of anti-CCP antibody titers and ESR were significantly higher in patients with erosive disease than those in non-erosive RA patients (p < 0.001 and 0.0341) respectively. Moreover, a higher frequency of elevated titers of anti-CCP antibodies was found in RA patients with erosions compared to patients with non-erosive RA (78.3% vs. 43.2% respectively). The ROC curves of anti-CCP passed closer to the upper left corner than those other markers and area under the curve (AUC) of anti-CCP was significantly larger than AUC of other markers (0.755 for anti-CCP, 0.660 for ESR, 0.611 for CRP, 0.577 for RF, and 0.484 for MMP-3 female). A positive predictive value was higher for anti-CCP antibodies in comparison to other markers. We did not find significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as ESR or CRP. However, we confirmed the correlation of elevated titers of anti-CCP antibodies and RF in both groups of patients whereas the degree of correlation was more significant in non-erosive patients. CONCLUSION: The results of our study suggest that the presence of elevated anti-CCP antibody titers have better diagnostic performance than MMP-3, RF, CRP and ESR in patients with erosive RA.     

Serum oxidation activities and rheumatoid arthritis

The serum oxidation activity (SOA) of patients with rheumatoid arthritis (RA) and other connective-tissue diseases (OCTD) was measured by a new colorimetric procedure the authors have devised, using o-phenylene diamine (OPD) as the indicator. A comparison was made between SOA and other clinical data, such as patient age, the particular stages of the disease and its total duration, number of joints with active synovitis, arthritic score, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), RA test results, rheumatoid arthritis haemagglutination titre (RAHA), ceruloplasmine (CP) and transferrin. Fifty-three out of 73 patients with RA (72.6%) and thirteen out of 34 patients with OCTD (38.2%) showed high levels of SOA (mean + 2SD of the control value). A significant correlation was noted between SOA and the number of joints with active synovitis, serum CP, CRP and ESR in RA patients. SOA and lipid peroxide (LP) were inversely correlated to a very significant extent. In OCTD, SOA showed a significant correlation with CP, but not with CRP or ESR. The number of active synovitis in RA patients indicated their high correlation with SOA. Drugs generally used for RA therapy, such as D-penicillamine and tiobutarit (SA96), were found to have anti-oxidant activity in the presence of RA sera. On the basis of these data, it is apparent that SOA is a reliable indicator of RA activity, and that the oxidation of various body constituents and fluids may be essential to the inflammatory processes of RA.     

泌乳素促进类风湿关节炎患者外周血单个核细胞分泌白细胞介素-6

目的:探讨类风湿关节炎(RA)患者血清泌乳素(PRL)水平与疾病活动程度的关系,以及PRL促进外周血单个核细胞(PBMCs)分泌白细胞介素-6(IL-6)的机制。方法:收集我院2015年3月至9月40例初治RA患者临床及实验室资料。采用化学发光免疫分析法(CLIA)检测血清PRL水平,ELISA检测IL-6水平,RT-q PCR检测泌乳素受体(PRLR)mRNA的表达,Western blot法检测MAPK通路相关蛋白p-p38的蛋白水平。结果:RA患者血清PRL水平明显升高(P0.01),活动期RA患者PRL水平明显高于非活动期RA患者(P0.01)。PRL水平与DAS28评分、ESR和CRP呈正相关(P0.01)。RA患者PBMCs中PRLR水平明显升高(P0.01)。PRL可诱导PBMCs分泌IL-6,siRNA沉默PRLR或采用MAPK通路抑制剂可抑制IL-6的产生。结论:RA患者血清PRL升高与DAS28评分、ESR和CRP呈正相关,PRL可作为预测RA严重程度的指标。PRL通过与PRLR相互作用,激活p38 MAPK通路,从而促进IL-6分泌。     

Soluble HLA-DR antigen levels in serum correlate with rheumatoid arthritis disease activity and the presence of disease-associated epitopes

We investigated correlations between soluble HLA-DR (sHLA-DR) molecules and several clinical, biological and genetic parameters associated with rheumatoid arthritis (RA) disease activity. Serum sHLA-DR concentrations were determined in 146 samples from 89 RA patients by an ELISA format, using an antibody combination of mouse and rat monoclonal anti-human HLA-DR antibodies. The mean sHLA-DR serum level in RA patients was significantly increased with 277+/-19 ng/ml compared to 142+/-13 ng/ml of 80 healthy controls (P<0.001). In ascending order of significance, correlations were found between serum sHLA-DR and EULAR swelling and pain scores, Waaler-Rose, RA factor, ESR and CRP (P=0.025 to P<0.001). High sHLA-DR levels were defined above 374 ng/ml that was the 95% confidence interval of the controls. Thirty-seven blood samples (25%) in 31 RA patients were above this level. The EULAR pain and swelling scores, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and RA factor were higher (P=0.044 to P<0.001) at the moment of high sHLA-DR concentrations, compared to the lower concentrations. Higher disease activity was further found in groups of RA patients respectively heterozygous or homozygous for the disease-associated epitope (Q)R/KRAA within the HLA-DRB1 chain, compared to the group without this epitope (P<0.017 for part of the results). Likewise, sHLA-DR was respectively 169+/-17 (no disease associated epitope), 324+/-34 (heterozygous) and 442+/-69 ng/ml (homozygous for the disease-associated epitope on HLA-DRB1 alleles) (P<0.017). In conclusion, this study shows significant correlations between serum sHLA-DR levels and RA disease activity parameters, as well as increased sHLA-DR in patients with disease-associated epitope on HLA-DRB1 alleles.     

类风湿性关节炎患者的血清脂蛋白a水平与炎症指标相关性分析

目的 通过对类风湿性关节炎(RA)患者组与对照组(正常健康者)脂蛋白a(Lp-a)与脂代谢水平的比较,分析RA患者血清中的Lp-a水平与系统性炎症进展的风险相关性.方法 选取30例RA患者(血清类风湿因子阳性)与30例正常健康者,年龄为25～80岁,性别分布相同,采集血样并检测其脂代谢水平(Lp-a、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和极低密度脂蛋白胆固醇(VLDL-C))与炎症反应指标(肿瘤坏死因子α(TN F-α)、白细胞介素6(IL-6)和C反应蛋白(CRP)),对数据进行统计学分析.结果 与对照组比较,RA患者组的血清Lp-a水平显著增高(P＜0.001),HDL-C水平显著降低(P＜0.05),而TC、TG、LDL-C与VLDL-C水平则无明显变化,差异均无统计学意义(P＞0.05).同时,RA患者组的TNF-α、IL-6及CRP水平较对照组均显著增高(P＜0.05),且TNF-α与Lp-a水平的升高有相关性(r=0.753,P＜0.001).结论 RA患者常伴有高水平的Lp-a,且Lp-a水平的升高与RA患者的全身性炎症反应增强具有相关性,Lp-a水平可作为RA患者的风险评价指标.