| OBJECTIVE①The B cells in systemic erythematosus lupus(SLE) patients are active,and Epstein-Barr virus(EBV) is addicted with B cells,which leads to B cells activation.By detecting EBV DNA copy number,to investigate its associaton with SLE pathogenesis and SLE disease activity index(SLEDAI).②EBV has two infection states,latent infection and lytic infection.The expressions of antigens are different in the two states.Some regions of antigens are very simiar to specific antibodies of SLE,leading B cells to produce different self-antibodies by cross-reaction.By detecting gene expression of different infection states,to investigate its associaton with SLE pathogenesis and SLEDAI.③Different antigens are expressed in different infection states.Different bodies have different strength of immune response to different antigens,producing different types and concentrations of anti-EBV antibodies.By detecting the serum level of anti-EBV antibodies in different infection states,to investigate its associaton with SLE pathogenesis and SLEDAI.METHODSReal-time fluorescent quantitative PCR was used to direct EBV loads,mRNA expression levels of latent gene BKRF1,lytic gene BcLF1 and BLLF1 in periphery blood mononuclear cell(PBMC) of 55 SLE patients and 52 healthy controls,which encoded protein EBNA-1,VCA and gp350/220,respectively.Enzyme-Linked Immunosorbnent Assay(ELISA) was used to direct the serum level of VCA IgG,VCA IgM,EBNA-1 IgG of 44 SLE patients and 43 healthy controls,and to analyze the associations between the EBV loads,mRNA expression levels,antibody levels and SLE pathogenesis and SLEDAI.RESULTS1.The association between EBV DNA copy number and SLE pathogenesis, SLEDAI, self-antibodies.The EBV DNA median loads in 55 cases of SLE patients were 19.46copies/ug, significantly higher than 3.31copies/ug in 52 cases of healthy controls(t=2.246, P=0.027).The EBV DNA median loads in ten newly diagnosed SLE patients who were relatively stable(the mean SLEDAI was 6.5) were 68.27copies/ug,but increase to 1530.00copies/ug when in flare(the mean SLEDAI was 13.4),and the paired t-test had statistical significance(t=3.262,P=0.031).Among the 55 cases of SLE patients, there were 25 cases whose courses were within a year,and the EBV DNA median loads were 36.57copies/ug,higher than 29.76copies/ug in 30 cases beyond a year(t=2.532, P=0.019).23 cases of SLE patients in the group of 20-30 years had more EBV loads(median 65.9copies/ug) than those over 40 years of age(median 41.1copies/ug) (t=2.069,P<0.05),and had higher positive rates of anti-Sm and anti-SSA antibodies than patients of other ages(X2=7.848,P=0.049;X2=7.857,P=0.049).2.The association between gene expression levels in different infection states and SLE pathogenesis,SLEDAI.The positive rate of BLLFl in 55 cases of SLE patients was 77.6%,significantly higher than 59.6% in 52 cases of healthy controls(X2=5.360,P=0.021),and the expression levels of BLLF1 in 55 cases of SLE patients were 0.000103±0.139081,also significantly higher than 0.000006±0.456916 in 52 cases of healthy controls(t=3.333,P=0.002).The expression levels of BLLF1 in 55 cases of SLE patients had positive correlation with SLE disease activity index(r=0.343,P=0.003).The positive rates and expression levels of BKRF1 and BcLFl both had not statistical significance between SLE patients and healthy controls (1=1.132,P=0.260;t=0.579,P=0.566).3.The association between anti-EBV antibodies in different infection states and SLE pathogenesis,SLEDAI.The positive rate of VCA-IgG antibody was significantly greater by Chi square analysis in the serum from SLE patients than controls(90.91% of patients,74.42% of controls; X2=4.145,P=0.042).The median concentration in 40 patients of VCA IgG positive SLE patients was 30013.95U/ml,no difference with 31073.37U/ml in 32 cases of VCA IgG positive healthy controls(t=0.554,P=0.582).Four patients in 44 cases of SLE patients (9.09%) and 1 controls in 43 cases of healthy controls(2.33%)were positive for IgM anti-viral capsid antigen(VCA)(X2=1.838,P=0.175).The median concentration in 4 patients of VCA IgM positive SLE patients was 24044.51U/ml,no difference with 10065.21U/ml in 1 cases of VCA IgG positive healthy controls(t=1.348,P=0.270). Thirty-seven cases in 44 cases of SLE patients(84.09%) and forty-one controls in 43 cases of healthy controls(95.35%) were positive for IgG against EBNA-1(X2=2.972, P=0.085).The median concentration in 37 patients of EBNA-1 IgG positive SLE patients was 30013.95U/ml,no difference with 12452.25U/ml in 41 cases of EBNA-1 IgG positive healthy controls(t=0.099,P=0.921).CONCLUSIONinfection may be associated with the onset and relapse of SLE.②EBV infection may be engaged in the early period of SLE.③Those SLE patients in the age group of 20-30 years have active replication of EBV.④EBV makes B lymphocytes actively proliferate by lytic gene BLLFl,then B lymphocytes produce autoantibodies and induce subsequent clinical symptom.⑤The expression of lytic gene BLLF1 has positive association with SLE disease activity index.⑥The latent gene BKRF1 may be not associated with the onset of SLE.⑦The lytic gene BcLFl may be not associated with the onset of SLE.⑧The response to viral capsid antigen is stronger in SLE patients.⑨The recent EBV infection is related with SLE pathogenesis.⑩BNA-1-IgG antibody is an index of past infection and may be not associated with SLE. |
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