Expression Of PD-1 On T Lymphocytes And PD-L1 On Peripheral Blood Mononuclear Cells From The Patients With Systemic Lupus Erythematosus

Objective To investigate the expression of PD-1 on T lymphocytes and PD-L1 on peripheral blood mononuclear cells (PBMCs)from the patients with systemic lupus erythematosus(SLE)and analyze the clinical relevance to disease severity.Methods The expression of PD-1 on the subsets of T cells and PD-L1 on PBMCs were examined from 51 SLE patients ( included 33 active SLE,18 inactive SLE) and 38 healthy controls (HC) by the technique of the immunofluorescence and the flow cytometry.Clinical manifestations and laboratory findings of SLE were also collected.Patients were divided into two groups according to their SLE disease activity index(SLEDAI).SLEDAI score≥10 was defined as activity group and <10 as inactivity group .The percentage of PD-1 and PD-L1 was compared with inactive or active SLE patients and HC, and analyze its significance.Results①The percentage of CD4~+ PD-1~+ T cells and CD8~+ PD-1~+ T cells : Proportions of CD4~+ PD-1~+ T cells were significantly increased in active SLE patients (14.39±3.76)% as compared with inactive SLE patients (5.35±2.09)% and HC (4.89±2.56)%(P<0.05). No significant difference was observed between inactive SLE patients and HC. Proportions of CD8~+ PD-1~+ T cells were significantly increased in active(47.98±14.30)% and inactive SLE patients (24.85±6.41)% as compared with HC (16.92±4.53)%(P<0.05). Proportions of CD8~+ PD-1~+ T cells in active SLE patients were higher than that in inactive patients(P<0.05).②The percentages of PD-L1~+ cells in PBMCs in patients with SLE: Proportions of CD19+ PD-L1~+ B cells were significantly increased in inactive SLE patients (11.70±0.68)% as compared with that in active SLE patients(0.65±0.62)% and HC(0.43±0.24)% (P<0.05). No significant difference was observed between active SLE patients and HC. Proportions of CD14+ PD-L1~+ monocytes were significantly increased in active SLE patients (39.48±7.01)% as compared with inactive SLE patients (20.26±5.46)% and HC (10.21±4.50)%(P<0.05). Proportions of CD14+ PD-L1~+ monocytes in inactive SLE patients were higher than that in HC(P<0.05).③The percentages of CD4~+ PD-1~+ T cells or CD8~+ PD-1~+T cells and PD-L1 cells in PBMCs in SLE patients with or without nephritis: Proportions of CD4~+PD-1~+ T cells (13.40±5.05)% and CD8~+ PD-1~+ T cells (46.46±15.70)% in SLE patients with nephritis were respectively higher than those in patients without nephritis [(30.31±12.44)%, P=0.001; (30.31±12.44)%, P=0.000]. Proportions of PD-L1~+ T cells(18.95±9.00)% and of PD-L1~+B cells (1.46±0.83)% were significantly increased in SLE patients with nephritis as compared those without nephritis [(9.90±8.38)%, P=0.002; (0.71±0.66)%, P=0.000, respectively]. Proportions of PD-L1 on monocytes (26.41±10.42)% in SLE patients without nephritis were lower than those in SLE patients with nephritis [ (37.10±9.82)%, P=0.001].④The percentages of CD4~+ PD-1~+T cells or CD8~+ PD-1~+T cells and PD-L1~+ cells in peripheral blood mononuclear cells in SLE patients with or without anti-dsDNA: Proportions of CD4~+ PD-1~+ (13.22±4.84) % and CD8~+ PD-1~+(45.97±15.27)% T cells in SLE patients with positive anti-dsDNA were respectively higher than those in SLE patients with negative anti-dsDNA[(8.54±5.11)%,P=0.002;(31.71±14.47)%,P=0.001 respectively].Proportions of PD-L1~+ B cells (17.55±9.34)% and PD-L1~+(1.36±0.89)% T cells in SLE patients without anti-dsDNA were respectively higher than those in SLE patients with anti-dsDNA[(10.65±8.95)%,P=0.016;(0.76±0.66)%,P=0.037, respectively]. Proportions of PD-L1~+ cells in monocytes (25.04±10.63)% in SLE patients without anti-dsDNA were lower than those in SLE patients with anti-dsDNA [(38.51±7.89)%, P=0.000.].⑤The relationships between percentages of CD4~+ PD-1~+ T cells or CD8~+ PD-1~+ T cells and PD-L1~+ cells in PBMCs in SLE patients and SLEDAI: A positive correlation was observed for proportios of CD4~+ PD-1~+ and CD8~+ PD-1~+ T cells with the SLEDAI score(r=0.830, P<0.01; r=0.804, P<0.01,respectively). Proportios of PD-L1~+ B cells and PD-L1~+ T cells were inversely correlated with SLEDAI score(r=﹣0.813, P<0.01; r=﹣0.643, P<0.01, respectively). Proportios of PD-L1~+ cells in monocytes were positively correlated with SLEDAI score(r=0.884, P<0.01).⑥The relationships between percentages of CD4~+ PD-1~+ T cells or CD8~+ PD-1~+ T cells and PD-L1~+ cells in PBMCs in SLE patients and amounts of proteinuria: A positive correlation was observed for proportios of CD4~+PD-1~+ or CD8~+ PD-1~+ T cells and PD-L1~+ cells in monocytes with the amounts of proteinuria(r=0.475, P<0.01; r=0.358, P<0.05; r=0.436, P<0.01, respectively). Proportios of PD-L1~+ B cells were inversely correlated with amounts of proteinuria(r=-0.524, P<0.01).⑦The relationships between percentages of CD4~+ PD-1~+ T cells or CD8~+ PD-1~+ T cells and PD-L1~+ cells in PBMCs in SLE patients and complement 3(C3) levels: A negative correlation was observed for proportios of CD4~+ PD-1~+ or CD8~+ PD-1~+ T cells and PD-L1~+ cells in monocytes with the level of C3(r=-0.403, P<0.01; r=-0.439, P<0.01; r=-0.574, P<0.01, respectively). Proportions of PD-L1~+ T cells and PD-L1~+ B cells were positively correlated with C3 (r=0.440, P<0.01; r=0.382, P<0.01)Conclusions⑴Systemic lupus erythematosus disease state, the expression of PD-1 on the surface of the CD4 +, CD8 + T lymphocytes were increased, the expression of PD-L1 on the surface of T lymphocytes, B lymphocytes and monocytes are increased.⑵Systemic lupus erythematosus disease state, PD-1~+ CD4~+, PD-1~+ CD8~+ T lymphocyte percentage, and PD-L1~+ monocyte percentage were positively correlated with disease activity.⑶Systemic lupus erythematosus disease state, PD-L1~+T lymphocytes, PD-L1~+ B lymphocyte percentage were negatively correlated with disease activity .