Effects Of An Optimized BLyS Antagonist On Autoimmune Disease Animal Models

B lymphocyte stimulating factor(BLyS),a member of tumor necrosis factor(TNF)superfamily,is a key factor for B lymphocyte cell growth and differentiation.Through binding with the three receptors on the surface of cells,BLyS plays an important role in immune regulation.Several studies have shown that over-expression BLyS was closely related with the development of rheumatoid arthritis(RA),systemic lupus erythematosus(SLE)and other autoimmune disease,and the study of BLyS and its receptors’ antagonists are being on the attention of people.At present,BLyS antagonists mainly include: BLyS monoclonal antibodies,BLyS receptor-Ig fusion proteins and BLyS antagonist peptide-Fc fusion proteins.Belimumab,a monoclonal antibody against soluble BLyS,has been approved for treating SLE by FDA in 2011,which indicates that BLyS antagonists have good prospects in the treatment of autoimmune disease.Based on our previous research work,in this study,an optimized BLyS antagonist peptide-Fc fusion protein(TC-Linker-Fc)was obtained,using prokaryotic expression technique,and then investigated its prophylactic effect on animal models of autoimmune disease such as RA and SLE through experiments in vitro and in vivo.The results suggested that TC-Fc could efficiently bind with BLyS and inhibit the interactions between BLyS and its receptor TACI in a dose-dependent manner.In collage II induced rheumatoid arthritis(CIA)animal model experiments,after prophylactic treatment with TC-Fc,the clinical index and arthritis incidence of CIA mice were decreased obviously,as well as the ratios of B and Th cells significantly reduced in spleens.Compared with Fc group,TC-Fc fusion protein could inhibit synovial hyperplasia,joint space narrowing and even bone damage,and supressed the levels of autoantibodies IgG1 and IgG2 a increasing.In SLE animal model experiments,SLE-prone mice treated with TC-Fc fusion protein developed kidney disease slowly,with improved kidney disease and reduced levels of dsDNA and anti-ANA antibody in serum though without significance,which needs futher study to identify.Taken together,TC-Fc fusion protein can delay the onset and development of RA and SLE,which has the possibility to become the potential drug of RA and SLE.