The role and clinical significance of programmed cell death- ligand 1 expressed on CD19+B-cells and subsets in systemic lupus erythematosus.

BACKGROUND: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1)-targeted therapies have enhanced T-cell response and demonstrated efficacy in the treatment of multiple cancers. However, the role and clinical significance of PD-L1 expression on CD19+ B-cells and their subsets, with particular reference to systemic lupus erythematosus (SLE), have not yet been studied in detail. OBJECTIVE: The present study aimed to investigate PD-L1 expression on CD19+ B-cells and their subsets, in addition to exploring its possible role in Tfh-cell activation and B-cell differentiation in SLE. METHODS: Frequencies of CD19+ B-cells, their subsets, PD-L1 and Tfh cells in the peripheral blood of SLE patients and healthy controls (HCs) were determined using cytometry. The clinical data of SLE patients were recorded in detail, and the correlation between their laboratory parameters, clinical parameters and disease activity indices was statistically analyzed. CD19+PD-L1+B-cells and CD19+PD-L1- B-cells were sorted and cultured with a stimulant, following which the supernatants were collected for immunoglobulin G and anti-double stranded DNA detection via enzyme-linked immunosorbent assay. RESULTS: In SLE patients, CD19+B-cells and partial subgroups were enriched in peripheral blood. Also, the observed increase in the frequency of CD19+PD-L1+B-cells was significantly associated with a higher disease activity index. An in vitro culture test demonstrated that the amounts of anti-dsDNA and immunoglobulin G secreted by the CD19+PD-L1+B-cells of SLE patients and HCs were vastly different. In addition, a strong correlation existed between the frequencies of CD19+PD-L1+B-cells and defined Tfh cells of SLE patients. CONCLUSION: This study demonstrated that the expression of CD19+PD-L1+B-cells in the peripheral blood of SLE patients was abnormal, and that disease-related laboratory parameters and clinical indicators were correlated. CD19+PD-L1+B-cells were enriched and played a critical role in activating the pathogenic T-cell and B-cell responses in patients with SLE.

[The Study of Protective Effect of Paeoniflorin on Lung Injury in MRL/lpr Mice].

OBJECTIVE: To investigate the protective effects of paeoniflorin on the lung injury in systemic lupus erythematosus with mouse model. METHODS: Ten wild type mice and 40 MRL/lpr mice were used in this study. MRL/lpr mice were randomly assigned to MRL/lpr group,MRL/lpr + dexamethasone (1.5 mg/kg) group,MRL/lpr + paeoniflorin (20 mg/kg) group,and MRL/lpr + paeoniflorin (40 mg/kg). The levels of malondialdehyde (MDA) , superoxide dismutase (SOD) ,catalase (CAT) ,glutathione peroxidase (GSH-Px) in serum were detected. The serum levesl of inflammatory cytokines were measured. Lung pathological changes were determined by HE staining. The protein level of phospho-phosphatidylinositol-3 kinase (P-PI3K),phospho-serine-threonine kinase B(P-Akt) ,phospho-nuclear factor kappa B (P-NF-κB),phospho-inhibitor of nuclear factor kappa Bα (P-IκBα) were detected by Western blot. RESULTS: Paeoniflorin decreased serum level of MDA and increased the levels of SOD,CAT,GSH-PX,and decreased the levels of inflammatory cytokines. Paeoniflorin improved lung pathological changes and inhibited the protein levels of P-PI3K,P-Akt,P-NF-κBp65,and P-IκBα in the lung tissue of MRL/lpr mice. CONCLUSION: Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus.

[Protective effects of glycyrrhizic acid against lupus nephritis in MRL/lpr mice].

OBJECTIVE: To investigate protective effect of glycyrrhizic acid (GA) against lupus nephritis in MRL/lpr mice and explore its underlying mechanisms. METHODS: Forty MRL/lpr mice were randomized equally into blank control group, dexamethasone (1.5 mg/kg) group, GA (20 mg/kg) group, and GA (40 mg/kg) group with corresponding treatments for 7 days, with 10 wild-type mice as the control group. Serum levels of uric acid and creatinine and inflammatory cytokines in the serum and kidney were tested after the treatments using enzyme-linked immunosorbent assays (ELISA). The pathological changes in the kidneys were detected using HE staining, and the protein expressions of NLRP3, ASC, caspase-1, IL-1ß, p-NF-κB, NF-κB, p-IκBα, and IκBα were detected with Western blotting. RESULTS: GA obviously decreased serum levels of uric acid and creatinine, decreased inflammatory cytokines in the serum and kidney, ameliorated renal pathologies and inhibited the expressions of NLRP3, ASC, caspase-1, IL-1ß, p-NF-κB, and p-IκBα proteins in MRL/lpr mice. CONCLUSION: GA has protective effects against lupus nephritis in MRL/lpr mice.

[Expression and clinical significance of PD-L1 on CD14⁺ monocyte in the peripheral blood of patients with systemic lupus erythematosus].

AIM: To detect expression of (programmed death ligand 1, PD-L1)on CD14(+) Monocyte(Mo)in the patients with systemic lupus erythematosus(SLE)and their clinical significance is analyzed. METHODS: The expression of PD-L1 on the CD14(+) Mo was examined in patients with 51 active SLE and 38 healthy controls(HC) by flow cytometry. The proportions of expression of PD-L1 on CD14(+) Mo were compared between not only inactive or active SLE patients and healthy controls(HC), but also between patients with lupus nephritis and without lupus nephritis. Correlation with clinical manifestations and laboratory findings was analyzed. RESULTS: The Proportions of CD14(+) PD-L1(+) Mo were significantly increased in active and inactive SLE patients as compared with HC(all P<0.05). The proportions of CD14(+) PD-L1(+) Mo in SLE patients with nephritis were significantly higher than those in patients without nephritis. A positive correlation was observed for proportions of CD14(+) PD-L1(+) Mo with SLEDAI score, and amounts of proteinuria. Proportions of CD14(+) PD-L1(+) Mo in SLE patients with anti-dsDNA, anti-Sm, anti-U1RNP and anti-nucleosome were higher than those in SLE patients without those antibody(P<0.05). CONCLUSION: The aberrations of proportions of CD14(+) PD-L1(+) Mo were observed in patients with SLE. Proportions of CD14(+) PD-L1(+) Mo were correlated with disease activity and production of antibody.

[The expression and clinical significance of IL-17AR on peripheral blood B cells of patients with systemic lupus erythematosus].

AIM: To investigate the expressions of Interleukin-17A receptor (IL-17AR) on the peripheral blood B lymphocytes of SLE patients and to analyze the correlations between IL-17AR and clinical parameters. METHODS: Expression of IL-17AR on peripheral blood CD19(+);B lymphocytes were analyzed in 60 SLE patients and 33 healthy controls by flow cytometry. The difference of IL-17AR expression levels in two groups were compared. Furthermore, the correlation between IL-17AR expressions and clinical some measures, such as ESR, CRP, complement 3(C3), complement 4(C4), the amount of serum IgG, anti double strands DNA antibody, anti nuclear antibody, SLEDAI score and urine protein excretion were analyzed. RESULTS: Compared with healthy subjects, the proportions of B cells expressing IL-17AR were higher among SLE patients. In SLE patients, groups with mouth ulcer, serositis, renal lesions or immunologic abnormality were higher than the negative groups separately. The positive correlations were observed between IL-17AR expression levels and clinical measure of the SLEDAI, CRP and serum triglyceride level. The negative correlation was observed between IL-17AR expression levels and clinical measure of the serum indirect bilirubin level, serum albumin level. CONCLUSION: Interleukin-17A receptor expression increased on peripheral blood B cells of SLE patients, and correlate with clinical measures.