目的探索类风湿性关节炎(rheumatoid arthritis,RA)中医辨证分型的客观基础,研究RA各证型类风湿因子(rheumatoid factor,RF)、抗环瓜氨酸肽(citrullinated protein antibody,CCP)抗体分型差异。方法选择230例早期RA患者,按证型分为湿热...目的探索类风湿性关节炎(rheumatoid arthritis,RA)中医辨证分型的客观基础,研究RA各证型类风湿因子(rheumatoid factor,RF)、抗环瓜氨酸肽(citrullinated protein antibody,CCP)抗体分型差异。方法选择230例早期RA患者,按证型分为湿热痹阻(50例)、寒湿痹阻(50例)、肾气虚寒(50例)、肝肾阴虚(40例)、瘀血痹阻组(40例),另选择体检健康者100名作为健康对照组。比较各组血清类风湿因子——RF-IGM、RF-IGA、RF-IGG、抗CCP抗体。结果湿热痹阻、寒湿痹阻、肾气虚寒、肝肾阴虚、瘀血痹阻组抗CCP抗体及RF-IGM、RF-IGA、RF-IGG浓度均高于健康对照组(P<0.01);各组活动期抗CCP抗体及RFIGM、RF-IGA、RF-IGG高于非活动期(P<0.05);活动期湿热痹阻型抗CCP抗体及RF-IGM、RF-IGA、RF-IGG浓度高于肾气虚寒、肝肾阴虚、瘀血痹阻型(P<0.01)。结论类风湿因子RF-IGM、RF-IGA、RF-IGG、抗CCP抗体浓度可作为RA中医辨证分型的客观实验室指标和活动期的判定指标。展开更多
背景:抗瓜氨酸化蛋白抗体是类风湿关节炎特异性、早期诊断标志物,与类风湿关节炎发生发展及骨破坏的加重密切相关,该类抗体阳性患者的病情比阴性患者更严重而且更难治疗。胶原诱导型关节炎和佐剂诱导型关节炎等是典型的2种类风湿关节炎...背景:抗瓜氨酸化蛋白抗体是类风湿关节炎特异性、早期诊断标志物,与类风湿关节炎发生发展及骨破坏的加重密切相关,该类抗体阳性患者的病情比阴性患者更严重而且更难治疗。胶原诱导型关节炎和佐剂诱导型关节炎等是典型的2种类风湿关节炎动物模型,但都不表达或不能稳定高水平表达抗瓜氨酸化蛋白抗体,从而严重影响了抗瓜氨酸化蛋白抗体阳性类风湿关节炎发病机制和治疗药物研发的深入研究。目的:通过查阅国内外相关文献,综合分析抗瓜氨酸化蛋白抗体高表达的类风湿关节炎动物模型的研究现状,指出存在问题并提出建议。方法:以“Rheumatoid Arthritis,ACPA”或“Rheumatoid Arthritis,anti-CCP”为英文检索词,以“类风湿关节炎、抗瓜氨酸化蛋白抗体”为中文检索词,通过检索PubMed、Web of Science、中国知网、万方及维普数据库中2021年8月前发表的相关文献,最终纳入文献61篇进行综述分析。结果与结论:①抗瓜氨酸化蛋白抗体高表达的类风湿关节炎动物模型建立的主要方法有抗瓜氨酸化蛋白抗体单克隆抗体诱导、瓜氨酸化蛋白诱导和牙龈卟啉单胞菌诱导等,不同的造模方法各有特点。②瓜氨酸化蛋白诱导模型报道文献最多、建模后动物关节炎特征最明显,且该类蛋白为类风湿关节炎发病的靶抗原之一,能很好地模拟人体病理变化,当属建模首选模型。③氨酸化蛋白诱导和抗瓜氨酸化蛋白抗体单克隆抗体诱导方式类似,但均具有造模剂制备繁琐和难以获得的缺点。④牙龈卟啉单胞菌诱导模型经济成本较低、造模材料相对简单易得,但缺陷是建模后易合并牙周炎等并发症。⑤因此,未来研究寻找合适的抗瓜氨酸化蛋白抗体单克隆抗体、瓜氨酸化蛋白或短肽作为免疫诱导剂,并选择遗传背景和免疫学因素与人类风湿关节炎发病适合的动物,探寻牙龈卟啉单胞菌展开更多
Because of genetic complex and variations of auto antibodies of rheumatoid arthritis (RA) in different populations, the data on the association of HLA-DRB1 alleles in anti-citrullinated protein antibody of (ACPA) RA w...Because of genetic complex and variations of auto antibodies of rheumatoid arthritis (RA) in different populations, the data on the association of HLA-DRB1 alleles in anti-citrullinated protein antibody of (ACPA) RA were inconsistent. The purpose of the study is to systematically summarize results of published data through performing a meta-analysis using data in which HLA-DRB1 alleles are associated with ACPApositive RA and ACPA-negative RA. In this study, we collected data from 12 studies with 13,861 cases and 12,896 controls. Information in these studies included HLADRB1 typing and ACPA status from different countries. Odds ratios (ORs) and corresponding 95% confidence intervals (CI) were used to analyze the association of different HLA-DRB1 alleles with ACPA-positive RA or ACPA-negative RA. To correct skewing data, the analysis of ACPA-status was stratified by patient distribution. Our analyses indicate that in ACPA-positive RA, all patients with RA had significantly higher frequencies of HLA-DRB1*01, *04, *0401, *0405, *07, *11, *13 and *14 than controls. One of the HLA-DRB1*07, *11, *13 and *14 showed protective association with RA. In addition, HLA-DRB1*03, *10 and *12 had more influence than control to RA in European populations;the HLA-DRB1*03 and *12 alleles were associated with the protection. In ACPA-negative RA, only DRB1*07 was associated with the protection (OR 0.53 [95% CI 0.36 - 0.76]) among all HLA-DRB1 alleles in European populations. In ACPA-positive RA, currently available results indicate that *01, *04, *0401 and *0405 are susceptible, while HLA-DRB1*07, *11, *13 and *14 are protective in all populations. While the HLA-DRB1*10 is susceptible, HLA-DRB1*03 and *12 show protective association with RA in European populations. Additionally, regardless of the positive or negative ACPA, the DRB1*07 is always associated with protection in European populations.展开更多
文摘目的探索类风湿性关节炎(rheumatoid arthritis,RA)中医辨证分型的客观基础,研究RA各证型类风湿因子(rheumatoid factor,RF)、抗环瓜氨酸肽(citrullinated protein antibody,CCP)抗体分型差异。方法选择230例早期RA患者,按证型分为湿热痹阻(50例)、寒湿痹阻(50例)、肾气虚寒(50例)、肝肾阴虚(40例)、瘀血痹阻组(40例),另选择体检健康者100名作为健康对照组。比较各组血清类风湿因子——RF-IGM、RF-IGA、RF-IGG、抗CCP抗体。结果湿热痹阻、寒湿痹阻、肾气虚寒、肝肾阴虚、瘀血痹阻组抗CCP抗体及RF-IGM、RF-IGA、RF-IGG浓度均高于健康对照组(P<0.01);各组活动期抗CCP抗体及RFIGM、RF-IGA、RF-IGG高于非活动期(P<0.05);活动期湿热痹阻型抗CCP抗体及RF-IGM、RF-IGA、RF-IGG浓度高于肾气虚寒、肝肾阴虚、瘀血痹阻型(P<0.01)。结论类风湿因子RF-IGM、RF-IGA、RF-IGG、抗CCP抗体浓度可作为RA中医辨证分型的客观实验室指标和活动期的判定指标。
文摘背景:抗瓜氨酸化蛋白抗体是类风湿关节炎特异性、早期诊断标志物,与类风湿关节炎发生发展及骨破坏的加重密切相关,该类抗体阳性患者的病情比阴性患者更严重而且更难治疗。胶原诱导型关节炎和佐剂诱导型关节炎等是典型的2种类风湿关节炎动物模型,但都不表达或不能稳定高水平表达抗瓜氨酸化蛋白抗体,从而严重影响了抗瓜氨酸化蛋白抗体阳性类风湿关节炎发病机制和治疗药物研发的深入研究。目的:通过查阅国内外相关文献,综合分析抗瓜氨酸化蛋白抗体高表达的类风湿关节炎动物模型的研究现状,指出存在问题并提出建议。方法:以“Rheumatoid Arthritis,ACPA”或“Rheumatoid Arthritis,anti-CCP”为英文检索词,以“类风湿关节炎、抗瓜氨酸化蛋白抗体”为中文检索词,通过检索PubMed、Web of Science、中国知网、万方及维普数据库中2021年8月前发表的相关文献,最终纳入文献61篇进行综述分析。结果与结论:①抗瓜氨酸化蛋白抗体高表达的类风湿关节炎动物模型建立的主要方法有抗瓜氨酸化蛋白抗体单克隆抗体诱导、瓜氨酸化蛋白诱导和牙龈卟啉单胞菌诱导等,不同的造模方法各有特点。②瓜氨酸化蛋白诱导模型报道文献最多、建模后动物关节炎特征最明显,且该类蛋白为类风湿关节炎发病的靶抗原之一,能很好地模拟人体病理变化,当属建模首选模型。③氨酸化蛋白诱导和抗瓜氨酸化蛋白抗体单克隆抗体诱导方式类似,但均具有造模剂制备繁琐和难以获得的缺点。④牙龈卟啉单胞菌诱导模型经济成本较低、造模材料相对简单易得,但缺陷是建模后易合并牙周炎等并发症。⑤因此,未来研究寻找合适的抗瓜氨酸化蛋白抗体单克隆抗体、瓜氨酸化蛋白或短肽作为免疫诱导剂,并选择遗传背景和免疫学因素与人类风湿关节炎发病适合的动物,探寻牙龈卟啉单胞菌
文摘Because of genetic complex and variations of auto antibodies of rheumatoid arthritis (RA) in different populations, the data on the association of HLA-DRB1 alleles in anti-citrullinated protein antibody of (ACPA) RA were inconsistent. The purpose of the study is to systematically summarize results of published data through performing a meta-analysis using data in which HLA-DRB1 alleles are associated with ACPApositive RA and ACPA-negative RA. In this study, we collected data from 12 studies with 13,861 cases and 12,896 controls. Information in these studies included HLADRB1 typing and ACPA status from different countries. Odds ratios (ORs) and corresponding 95% confidence intervals (CI) were used to analyze the association of different HLA-DRB1 alleles with ACPA-positive RA or ACPA-negative RA. To correct skewing data, the analysis of ACPA-status was stratified by patient distribution. Our analyses indicate that in ACPA-positive RA, all patients with RA had significantly higher frequencies of HLA-DRB1*01, *04, *0401, *0405, *07, *11, *13 and *14 than controls. One of the HLA-DRB1*07, *11, *13 and *14 showed protective association with RA. In addition, HLA-DRB1*03, *10 and *12 had more influence than control to RA in European populations;the HLA-DRB1*03 and *12 alleles were associated with the protection. In ACPA-negative RA, only DRB1*07 was associated with the protection (OR 0.53 [95% CI 0.36 - 0.76]) among all HLA-DRB1 alleles in European populations. In ACPA-positive RA, currently available results indicate that *01, *04, *0401 and *0405 are susceptible, while HLA-DRB1*07, *11, *13 and *14 are protective in all populations. While the HLA-DRB1*10 is susceptible, HLA-DRB1*03 and *12 show protective association with RA in European populations. Additionally, regardless of the positive or negative ACPA, the DRB1*07 is always associated with protection in European populations.