B-cell targeted therapy is effective for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis(RA),although there are setbacks in RA clinical trials.In this study,we designed a novel B-cell...B-cell targeted therapy is effective for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis(RA),although there are setbacks in RA clinical trials.In this study,we designed a novel B-cell activating factor(BAFF)antagonist:BAFF-Trap,a recombinant glycoprotein with BAFF-binding domains of two BAFF receptors(TACI and Br3)linked to Fc domain of human IgG1.Unlike TACI-Fc,BAFF-Trap bound BAFF but not APRIL(a proliferation-inducing ligand),and significantly suppressed the development of collagen-induced arthritis and adjuvant-induced arthritis.Furthermore,BAFF-Trap inhibited proinflammatory cytokine expression,ameliorated joint damage and suppressed B-and T-cell activation.BAFF-Trap reduced dendritic cells in joints,and increased regulatory T cell,regulatory B-cell,and M2 macrophage.The function of BAFF-Trap was related to inhibition of canonical and noncanonical NF-κB activation.Thus,BAFF-Trap may be a valuable agent for the effective treatment of RA.展开更多
To the Editor:Left ventricular diastolic dysfunction(LVDD)is an unrecognized subclinical presentation of autoimmune diseases(AD)andcarries a worse prognosis.Elevated serum uric acid(SUA),as a_proinflammatory factor,is...To the Editor:Left ventricular diastolic dysfunction(LVDD)is an unrecognized subclinical presentation of autoimmune diseases(AD)andcarries a worse prognosis.Elevated serum uric acid(SUA),as a_proinflammatory factor,is associatedwithchanges in cardiacfunction in the general population as,well as in those with cardiac diseases.展开更多
基金This study was supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2012ZX09103301-025,No.2018ZX09201018-013,and No.2018ZX09733001)China Postdoctoral Science Foundation(No.2018M633370).
文摘B-cell targeted therapy is effective for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis(RA),although there are setbacks in RA clinical trials.In this study,we designed a novel B-cell activating factor(BAFF)antagonist:BAFF-Trap,a recombinant glycoprotein with BAFF-binding domains of two BAFF receptors(TACI and Br3)linked to Fc domain of human IgG1.Unlike TACI-Fc,BAFF-Trap bound BAFF but not APRIL(a proliferation-inducing ligand),and significantly suppressed the development of collagen-induced arthritis and adjuvant-induced arthritis.Furthermore,BAFF-Trap inhibited proinflammatory cytokine expression,ameliorated joint damage and suppressed B-and T-cell activation.BAFF-Trap reduced dendritic cells in joints,and increased regulatory T cell,regulatory B-cell,and M2 macrophage.The function of BAFF-Trap was related to inhibition of canonical and noncanonical NF-κB activation.Thus,BAFF-Trap may be a valuable agent for the effective treatment of RA.
基金Science Technology Support Plan Projects of Sichuan Province(No. 2020YFS0241)135 project for disciplines of excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University(No. 2020HXFH045)。
文摘To the Editor:Left ventricular diastolic dysfunction(LVDD)is an unrecognized subclinical presentation of autoimmune diseases(AD)andcarries a worse prognosis.Elevated serum uric acid(SUA),as a_proinflammatory factor,is associatedwithchanges in cardiacfunction in the general population as,well as in those with cardiac diseases.
