RA患者外周血HLA-DR4、PAD4、STAT4 mRNA表达及与疾病活动的相关性

Association of HLA-DR4,PAD4,and STAT4 expression in the peripheral blood with disease activity in patients with rheumatoid arthritis

目的探讨类风湿关节炎(RA)患者外周血人类白细胞抗原(HLA)-DR4、Ⅳ型肽精氨酸脱亚氨基酶(PAD4)、信号转导与转录激活因子4(STAT4)的表达及与RA病情活动的关系。方法患者来源于南方医院中医风湿科专科门诊及病房,根据DAS28评分分为活动期RA患者24例(DAS28≥2.6),缓解期RA患者14例(DAS28<2.6),以12例健康体检者为对照组,采用Quanti Gene Plex(QGB)方法测定外周血HLA-DR4、PAD4、STAT4 mRNA表达水平。分析RA患者HLA-DR4、PAD4、STAT4 mRNA表达水平及与病情活动程度、抗环瓜氨酸(抗-CCP)抗体、类风湿因子(RF)的关系。结果与对照组相比,活动期、缓解期RA HLA-DR4 mRNA表达均上调(P<0.05),但两者比较差异无统计学意义(P>0.05);活动期RA PAD4 mRNA表达水平高于缓解期RA和对照组(P<0.05),缓解期RA较对照组表达升高(P<0.05),活动期RA STAT4 mRNA表达水平高于缓解期RA和对照组(P<0.05),缓解期RA和对照组两组表达水平无明显差异(P>0.05);RA患者HLA-DR4 mRNA表达与DAS28、抗-CCP抗体、RF均无相关性(P>0.05);PAD4 mRNA表达与DAS28、抗-CCP抗体水平呈正相关(P<0.05),STAT4 mRNA表达与DAS28、RF呈正相关((P<0.05)。结论 1、RA患者外周血HLA-DR4、PAD4、STAT4基因表达上调;2、HLA-DR4 mRNA表达水平与RA活动性无明显相关;PAD4、STAT4 mRNA表达水平与疾病活动密切相关。检测PAD4、STAT4 mRNA表达水平有助于对RA疾病活动的判断。

Objective To explore the association of the expressions of human leukocyte antigen（HLA）-DR4,peptidyl arginine deiminase type4（PAD4）,and signal transducer and activator of transcription 4（STAT4） in the peripheral blood with the disease activity in patients with rheumatoid arthritis（RA）.Methods Twenty-four RA patients in active stage（DAS28 score ≥ 2.6） and 14 RA patients in remission stage（DAS28 score2.6） were enrolled in this study,with 12 healthy volunteers as the control.The QuantiGene Plex method was used to measure the expression level of HLA-DR4,PAD4,and STAT4 mRNA,and the relationship between the expressions of these genes and the DAS28 score,levels of anti-cyclic citrullinated peptide antibody（anti-CCP antibody） and rheumatoid factor（RF） was analyzed.Results The expressions of HLA-DR4,PAD4,and STAT4 were significantly higher in RA patients than in the healthy controls（P0.05）.The level of HLA-DR4 mRNA in the two RA groups showed no significant difference,but was significantly higher than that in the healthy controls.HLA-DR4 expression was not found to correlated to DAS28 score,anti-CCP antibody level or RF in the RA patients.The expressions of PAD4 and STAT4 were significantly different between the two RA groups（P0.05）.In the RA patients,PAD4 mRNA expression was positively correlated to DAS28 and anti-CCP antibody level（P0.05）,and STAT4 expression showed positive correlations to DAS28 and RF levels（P0.05）.Conclusions HLA-DR4,PAD4 and STAT4 are overexpressed in RA patients and may be involved in the pathogenesis of RA.The expressions of PAD4 and STAT4,but not HLA-DR4,are closely related to the disease activity of RA.Detection of peripheral blood PAD4 and STAT4 expressions can be helpful for evaluating the disease activity of RA.