Role of ceRNA network in inflammatory cells of rheumatoid arthritis / 中南大学学报(医学版)

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.

Clinical significance of abnormally expressed PD-1 on CD4+CD28-and CD4+CD28+T cells in periph-eral blood of SLE patients / 中华微生物学和免疫学杂志

Objective To investigate the clinical significance of abnormally expressed PD-1 on CD 4+CD 2 8+/-T cells in peripheral blood of patients with systemic lupus erythematosus ( SLE ) . Methods Peripheral blood samples were collected form 50 patients with primary SLE and 40 healthy subjects and used to isolated mononuclear cells. Expression of CD4+CD28-, CD4+CD28+, CD4+CD28+PD-1+and CD4+CD28-PD-1+T cells in peripheral blood samples of the two groups were detected by flow cytometry. Clinical data of SLE patients were collected. Based on SLE disease activity index (SLEDAI), SLE patients were classified into two groups: stable group (SLEDAI<10) and active group (SLEDAI≥10). Based on the condition of renal damage, they were also divided into two groups: lupus nephritis group and non-lupus ne-phritis group. Differences in T cell expression were compared among these groups. Statistical analysis was performed to analyze the relationships of different T cell subsets with laboratory and clinical parameters rela-ting to SLE and SLEDAI. Results The percentages of peripheral CD4+CD28-, CD4+CD28+PD-1+and CD4+CD28-PD-1+T cells of active group were higher than those of stable and healthy control groups ( P<0. 05). Moreover, patients with lupus nephritis had higher percentages of these T cell subsets than those without (P<0. 01). SLE patients who were positive for anti-dsDNA or anti-SmRNP antibody, or had de-creased complement C3, thrombocytopenia or decreased lymphocytes had higher percentages peripheral CD4+CD28-T cells than those in the corresponding negative group. SLE patients who were positive for anti-dsDNA or anti-SmRNP antibody, or had decreased complement C3, complement C4 or lymphocytes showed en-hanced expression of peripheral CD4+CD28+PD-1+T cells as compared with those in the corresponding nega-tive group. SLE patients positive for anti-dsDNA antibody, or with decreased complement C3 or lymphocytes or suffering from alopecia had higher percentages of peripheral CD4+CD28-PD-1+T cell than those in the cor-responding negative group. Differences between different groups were statistically significant (P<0. 05). Conclusion Abnormal expression of CD4+CD28-T cells and PD-1 on CD4+CD28-and CD4+CD28+T cells in peripheral blood of patients with SLE has certain correlation with laboratory parameters and clinical indicators.

Effects of dexamethasone on MRL/Ipr mice with systemic lupus erythematosus complicated with cognitive dysfunction / 中南大学学报(医学版)

Objective:To evaluate the effects of dexamethasone on systemic lupus erythematosus complicated with cognitive dysfunction.Methods:Ten wild type mice and 20 MRL/lpr mice were applied for the research.MRL/lpr mice were randomly assigned to a MRL/lpr group and a MRL/lpr + dexamethasone (1.5 mg/kg) group.Interleukin-6 (IL-6),IL-1β,and tumor necrosis factor alpha (TNF-α) in serum and hippocampus were detected.The protein phosphorylation levels of phosphoinositide 3-kinase (P-PI3K),protein kinase B (P-Akt),NF-kappa-B inhibitor alpha (P-IκBa) and nuclear transcription factor kappa-B p65 (P-NF-κB p65) were detected by Western blot,the level of P-NF-κB p65 also was detected by immunohistochemistry.Results:Treatment with dexamethasone (1.5 mg/kg) alleviated the cognitive dysfunction and decreased the levels of IL-6,IL-1 β and TNF-α in serum and hippocampus,and reduced the levels of P-PI3K,P-Akt,P-IκBa and P-NF-κB p65 in hippocampus in MRL/lpr mice.Conclusion:Dexamethasone may play a protective role in the cognitive function by decreasing the levels of TNF-α and IL-1 β in the hippocampus of MRL/lpr lupus mice.

Expression and clinical significance of PD-1 on CD4+CD25high Tr and CD4+ CD25low T cells in the peripheral blood of patients with systemic lupus erythematosus / 中华微生物学和免疫学杂志

Objective To detect the frequency of peripheral blood CD4+ CD25high Tr and CD4+CD25lowT cells and expression of programmed death-1 ( PD-1 ) on their surface in the patients with systemic lupus erythematosus(SLE) and their clinical signifcance is analyzed.Methods The expression of PD-1 on the CD4+ CD25highTr and CD4+CD25lowT cells was examined in patients with 33 active SLE,18 inactive SLE and 38 healthy controls(HC) by flow cytometry.Clinical manifestations and laboratory findings of SLE were collected.Patients were divided into two groups according to their disease activity.SLE disease activity index(SLEDAI) score≥10 was defined as high disease activity and ＜10 as inactivity.The percentage of CD4+ CD25highTr and CD4+CD25lowT cells and proportions of expression of PD-1 on their surface 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 clincal manifestations and laboratory findings was analyzed.Results (1)The proportions of CD4+CD25highTr and CD4+CD25low T cells were significantly decreased in active and inactive SLE patients as compared with HC.(2)The percentage of CD4+ CD25lowPD-1 +Tr and in active and inactive SLE patients were higher than HC.The proportions of CD4+CD25lowPD-1+ T cells were significantly increased in HC and inactive SLE patients as compared with inactive SLE patients.(3) The proportions of CD4+CD25highPD-1+Tr in SLE patients with nephritis were higher than those in patients without nephritis.But the percentage of CD4+ CD25 lowPD-1 + T cells was significantly decreased in SLE patients with nephritis as compared those without nephritis.(4)A positive correlation was observed for proportions of CD4+CD25highPD-1 + T cells with SLEDAI score.Proportions of CD4+ CD25high Tr,CD4+ CD25low PD-1 + T cells was inversely correlated with SLEDAI score.Conclusion The aberrations of proportions of CD4+CD25highpD-1+,CD4+CD25lowPD-1+,CD4+CD25high and CD4+CD25low T cells were observed in patients with SLE.The abnormality of PD-1 and PD-L1 pathway may play an important role in the function and number of Tr.

The expression and clinical significance of Toll-like receptor 7 and 9 in peripheral blood B cells of patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective The aim of this study is to examine the expressions of Toll like receptor (TLR) 7 and TLR9 in the peripheral blood B lymphocytes of SLE patients and to analyze the correlation between TLR7/9 and clinical parameters. Methods lntracellular expression of TLR7/9 in the peripheral blood CD19+Blymphocytes was analyzed in 50 SLE patients and 30 healthy controls by flow cytometry. The difference of intracellular TLR7/9 expression levels in two groups was compared. Furthermore,the correlation between TLR7/9 expression and clinical parameters such as ESR, CRP, complement 3 (C3), complement 4 (CA), the level of serum IgG, anti-double stranded DNA antibody, anti-nuclear antibodies, SLEDAI score and urine protein excretion level, were analyzed. Results Compared with healthy subjects, the proportion of B cells expressing TLR7 and TLR9 was higher among SLE patients. Positive correlation was observed between TLR7 expression levels and clinical measurement of the SLEDAI and ESR. Negative correlation was observed between TLR7 expression levels and serum C3 levels. Positive correlation was observed between TLR9 expression levels and SLEDAI scores. Negative correlation was observed between TLR9 expression levels and serum C3 levels. Conclusion TLR7 and TLR9 expression is increased in the peripheral blood B cells of SLE patients, and correlates well with clinical parameters.

Nosocomial Bacterial Infection in Patients with Systemic Lupus Erythematosus:An Analysis of Clinical Features and Risk Factors / 中华医院感染学杂志

OBJECTIVE To investigate the clinical features and risks factors of nosocomial bacterial infection in patients with systemic lupus erythematosus(SLE).METHODS Five hundred and ninety-seven patients with SLE were classed into two groups,the group of nosocomial bacterial infection and the control group according to the results of bacteriological examinations.A comparison was performed between the two groups.RESULTS According to the infection sites,36% occurred in the respiratory tract and lungs,29.0% in the urinary tract,19.9% in the blood system and 15.1% in other tissues and organs.From them,75.8% onsets of nosocomial bacterial infection were chronic or insidious.The pathogens of nosocomial bacterial infection were mostly opportunistic,45.6% were G-bacilli,40.9% G+cocci and 13.9% were other bacteria.The eight major risk factors included lung disease,the more than 3 damaged organs or systems,plasma albumin under 30 g/L,long application of large dose glucocorticoid(GC),treatment of super-dose GC,therapeutic alliance of GC and cytotoxic immunosuppressant usage,use of broad-spectrum antibiotics before hospitalization and the time in hospital over 3 weeks.CONCLUSIONS The respiratory tract and lungs are the commonest site of nosocomial bacterial infection in patients with SLE.Most of the pathogens may be opportunistic of G-bacilli and G+cocci.The clinical features are untypical.It may decrease the incidence of the nosocomial bacterial infection to diminish by decreasing dose and the course of GC treatment after the patient's condition improved,select prudently application of super-dose GC,therapeutic alliance of GC and cytotoxic immunosuppressants,cautiously use of broad-spectrum antibiotics and shorten the duration of hospitalization.