OBJECTIVES:Anti-citrullinated protein antibodies(ACPAs)are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis(RA)biomarkers.ACPAs also play a crucial ro...OBJECTIVES:Anti-citrullinated protein antibodies(ACPAs)are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis(RA)biomarkers.ACPAs also play a crucial role in RA pathogenesis,and their underlying mechanism merits investigation.METHODS:Immunohistochemical(IHC)assays were carried out to determine IL-1βlevels in ACPA+and ACPA−RA patients.PBMCderived monocytes were differentiated into macrophages before stimulation with ACPAs purified from RA patients.The localization and interaction of molecules were analyzed by confocal microscopy,co-IP,and surface plasmon resonance.RESULTS:In our study,we found that IL-1βlevels were elevated in ACPA+RA patients and that ACPAs promoted IL-1βproduction by PBMC-derived macrophages.ACPAs interacted with CD147 to enhance the interaction between CD147 and integrinβ1 and,in turn,activate the Akt/NF-κB signaling pathway.The nuclear localization of p65 promoted the expression of NLRP3 and pro-IL-1β,resulting in priming.Moreover,ACPA stimulation activated pannexin channels,leading to ATP release.The accumulated ATP bound to the P2X7 receptor,leading to NLRP3 inflammasome activation.CONCLUSIONS:Our study suggests a new hypothesis regarding IL-1βproduction in RA involving ACPAs,which may be a potential therapeutic target in RA treatment.展开更多
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
基金This work was supported by the National Basic Research Program“973 Grants”(2015CB553704)the National Basic Research Program of China grant(2014ZX09508002-002)+1 种基金the National Key Research and Development Program of China grant(2017YFC0909000)We would also like to express our gratitude to Professor Zhinan Chen,who helped us design the experiments and provided us with essential experimental equipment.
文摘OBJECTIVES:Anti-citrullinated protein antibodies(ACPAs)are a group of autoantibodies targeted against citrullinated proteins/peptides and are informative rheumatoid arthritis(RA)biomarkers.ACPAs also play a crucial role in RA pathogenesis,and their underlying mechanism merits investigation.METHODS:Immunohistochemical(IHC)assays were carried out to determine IL-1βlevels in ACPA+and ACPA−RA patients.PBMCderived monocytes were differentiated into macrophages before stimulation with ACPAs purified from RA patients.The localization and interaction of molecules were analyzed by confocal microscopy,co-IP,and surface plasmon resonance.RESULTS:In our study,we found that IL-1βlevels were elevated in ACPA+RA patients and that ACPAs promoted IL-1βproduction by PBMC-derived macrophages.ACPAs interacted with CD147 to enhance the interaction between CD147 and integrinβ1 and,in turn,activate the Akt/NF-κB signaling pathway.The nuclear localization of p65 promoted the expression of NLRP3 and pro-IL-1β,resulting in priming.Moreover,ACPA stimulation activated pannexin channels,leading to ATP release.The accumulated ATP bound to the P2X7 receptor,leading to NLRP3 inflammasome activation.CONCLUSIONS:Our study suggests a new hypothesis regarding IL-1βproduction in RA involving ACPAs,which may be a potential therapeutic target in RA treatment.
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。
