Clinical Significance Of PD-1/PD-L1 Molecules Expressed By Dendritic Cells In Peripheral Blood Of Patients With Systemic Lupus Erythematosus

Background:Systemic lupus erythematosus(SLE)is a chronic autoimmune disease of unknown etiology that affects multiple systems and organs.Its typical characteristics are the body’s immune response to autoantigen disorder,the production of autoantibodies and inflammatory tissue damage.Dendritic cells play a central role in initiating the immune response and are responsible for the balance between immunity and tolerance.Continuous stimulation of dendritic cells(DC)by autologous antigens can enhance the activity of B cells,which are involved in the production of autoantibodies,and autoantibodies play an important role in the occurrence and development of SLE.There are important pathways to recognize and control PD-1molecular response in SLE,including the Toll-like receptor(TLR)pathway and the type I interferon(IFN)pathway,which are very active in the pathophysiology of SLE and the regulation of the PD-1 axis.Objective:This study was designed to investigate the expression of PD-1/PD-L1signaling pathway on DCs in peripheral blood of patients with Systemic Lupus Erythematosus(SLE),and to explore its possible role in the development and progression of systemic lupus erythematosus disease through clinical correlation studies.Methods:The expression of PD-1/PD-L1 molecular pathway on the surface of p DC and m DC cells in peripheral blood of SLE patients and healthy controls(HC)was detected by flow cytometry,and the correlation between PD-1 and PD-L1 molecular pathway and clinical and laboratory parameters was statistically analyzed.Plasma levels of IFN-and IFN-βin SLE patients and healthy controls(HC)were determined by enzymatic linked immunosorbent assay(ELISA),and their correlations with clinical and laboratory parameters were statistically analyzed.RESULTS:The expression of PD-1 on the surface of myeloid Dendritic cells(m DC)and plasmacytoid Dendritic cells(p DC)in peripheral blood of SLE patients was upregulated.Further studies showed that the cell frequencies of PD1~+L1~+p DC,PD1~+L2~+m DC,and PD1~+L2~+m DC in peripheral blood of SLE patients were increased,and were correlated with laboratory and clinical disease activity indicators such as decreased complement C3 and serum Ig M,and erythema butterfly and raynaud’s phenomenon.The serum concentration of IFN-αincreased in SLE patients,which was higher in the lupus nephritis group than in the non-lupus nephritis group,and positively correlated with serum complement C3 and C4.Conclusion:1.The abnormal expression of PD-1 in peripheral blood m DC and p DC cells as well as on the surface of SLE patients was correlated with some clinical and laboratory parameters.2.The frequencies of PD1~+L1~+p DC,PD1~+L2~+m DC,and PD1~+L2~+m DC cells in peripheral blood of SLE patients increased,and were correlated with laboratory and clinical disease activity indicators such as decreased complement C3 and serum Ig M,erythema butterfly and raynaud’s phenomenon,suggesting that the expression of PD-1/PD-L1 molecules by dendritic cells may play an important role in the pathogenesis of SLE.