HBV DNA Induced The Apoptosis Of CD8^highT Cells Play Different Roles In Patients With SLE And RA

Hepatitis B virus?HBV?is a high incidence of viral infection in China.In the past ten years when hepatitis B vaccine was included in planned immunization,the infection rate of hepatitis B virus showed a significant downward trend,but in the world,China is still a highly prevalent area.Autoimmune disease is characterized by the presence of autoreactive lymphocytes and circulating autoantibodies in the diseased tissues,that is,the overreaction of immunoglobulins to autoantigens.The occurrence of autoimmune diseases is the result of the joint action of genetic factors and environmental factors.therefore,a large number of studies are devoted to looking for environmental factors to control the incidence of autoimmune diseases.More and more clinical and epidemiological studies have shown that infection,especially hepatitis B virus infection,is involved in the pathogenesis and development of autoimmune diseases.Systemic lupus erythematosus?SLE?is a systemic autoimmune disease that can involve multiple organs and systems,such as skin and mucosa,skeletal muscle,heart and kidney,respiratory system,blood system,nervous system and so on.Systemic lupus erythematosus is characterized by an immune response to a variety of antinuclear autoantibodies.The etiology is not clear,but infection has been widely accepted as an important pathogenic factor.Rheumatoid arthritis?RA?is a serious multi-system inflammatory disease characterized by inflammatory synovitis,which often invades the facet joints of the hand and foot,and is characterized by symmetry.At the same time,it can be accompanied by extraarticular manifestations such as blood system and respiratory system involvement.Microbial infection has been recognized as the key cause of the disease.Reports on the prevalence of HBV in autoimmune diseases have been common in different countries and regions,but there are different explanations.Some studies have shown that the infection rate of HBV in patients with systemic lupus erythematosus is low,and patients with systemic lupus erythematosus have not reactivated HBV after receiving high doses of corticosteroids and immunosuppressants.Other studies have shown that HBV infection even plays a protective role in the development of systemic lupus erythematosus.In patients with rheumatoid arthritis,the infection rate of HBV is higher,and HBV infection is reactivated in patients with rheumatoid arthritis treated with biological agents.However,there is also literature that patients with rheumatoid arthritis have a lower prevalence of hepatitis B than healthy people.The relationship between HBV and rheumatoid arthritis is still largely unclear.A lot of evidence shows that HBV is an important cause of autoimmune diseases,and the role of HBV in autoimmune diseases is still the primary issue of related research.The link between HBV and autoimmune diseases is two-way.On the one hand,HBV infection may promote the secretion of proinflammatory cytokines by monocytes,interfere with the function of immune cells,induce the production of autoantibodies and trigger T cell-mediated autoimmunity,but the mechanism is still in the research stage.On the other hand,patients with autoimmune diseases have a higher risk of infection,which is related to the immune disorders of autoimmune diseases or immunosuppressive drugs,and its immune mechanism is still unclear.The prevalence of HBV in patients with systemic lupus erythematosus and rheumatoid arthritis is inconclusive,and the correlation between HBV infection and patients with systemic lupus erythematosus and rheumatoid arthritis needs to be determined.Objective: To investigate the prevalence of hepatitis B virus in patients with systemic lupus erythematosus and rheumatoid arthritis,to study the correlation between HBV and this two autoimmune diseases,to explore the relationship between T cell subgroups and disease activity of the two diseases,and the effect of HBV DNA on T cell subgroups in the two diseases.Methods: Collecting the information of patients with systemic lupus erythematosus and rheumatoid arthritis,obtaining the results of serological examination of hepatitis B,and calculating the prevalence of hepatitis B virus.Peripheral blood samples were collected from patients with systemic lupus erythematosus and rheumatoid arthritis.The patients were divided into inactive group and active group according to their disease activity.The plasma was separated and the expression of IFN-? was detected by enzyme linked immunosorbent assay?Elisa?.The expression levels of IFN-? in the two groups of patients were compared,and the differences of IFN-? levels between inactive and active patients were analyzed.The percentage of dendritic cells in monocytes,the expression of signal molecule CD86,the proportion of T cell subgroups in lymphocytes and the expression of suppressor molecule PD-1 were detected by flow cytometry.Peripheral blood mononuclear cells were isolated from the remaining whole blood by human peripheral blood lymphocyte separation solution.PBMC was stimulated by HBV DNA and IFN-? for 48 hours.The apoptosis of T cell subgroups was detected by flow cytometry.The infection rate of hepatitis B,the proportion of dendritic cells and the proportion of T cell subsets were analyzed by t-test,and the qualitative data were compared by analysis of variance.Results: 1.Hepatitis B infection rate in patients with RA is higher than that in patientswith SLE Statistical analysis of serological detection of hepatitis B in patients with RA and SLE showed that the infection rate of HBV in patients with RA was significantly higher than that in patients with SLE.2.Patients with hepatitis B infection and past infection are distributed in inactive SLE and active RA patients Patients with SLE and RA were divided into two groups: inactive and active.Statistical analysis showed that HBV infection and past infection were mainly distributed in inactive SLE patients,while for RA,HBV infection and past infection were mainly concentrated in active patients.3.The expression of IFN-? in patients with RA was significantly higher than that in patients with SLE,and the expression of IFN-? in patients with active RA was significantly higher than that in patients with inactive RA The levels of IFN-? in peripheral blood of patients with SLE and RA were detected by ELISA.The results showed that IFN-? was highly expressed in patients with SLE,and the expression level of IFN-? in peripheral blood of patients with RA was significantly higher than that in patients with SLE.After dividing the patients into two groups: inactive and active,we found that the level of IFN-? in active RA was significantly higher than that in inactive RA.4.The percentage of CD3⁺ T,CD8⁺ T and CD8^high T cells in patients with SLE was significantly higher than that in patients with RA T cell subgroups detected by flow cytometry showed that the proportion of CD3⁺ T,CD8⁺ T cells and CD8^high T cells in peripheral blood lymphocytes of patients with SLE was significantly higher than that in patients with RA.5.The expression of PD-1 in CD8^low T in patients with SLE was significantly higher than that in patients with RA The proportion of PD-1 of T cell subgroups were detected by flow cytometry,the results showed that the expression of PD-1 in CD8^low T subgroup of patients with SLE was significantly higher than that of patients with RA.6.In patients with SLE,the percentage of CD8⁺ T cells in active group was significantly higher than that in inactive group The results of T cell subgroups detected by flow cytometry showed that the proportion of CD8⁺ T cells in active group was higher than that in inactive group,and the proportion of CD8^high T cells in active patients was significantly higher than that in inactive patients.7.In patients with RA,the percentage of CD8⁺ T cells in active patients was significantly lower than that in inactive patients and healthy individuals The results of T cell subgroups detected by flow cytometry showed that the proportion of CD8⁺ T cells in group with active RA was significantly lower than that in inactive group and healthy individuals,and the proportion of CD8^high T cells in patients with active RA was also significantly lower than that in inactive patients and healthy indviduals.8.Among CD8^high T cells and DP T cells in patients with RA,the proportion of PD-1 in inactive group was significantly higher than that in active group and healthy individuals The results of T cell subgroups detected by flow cytometry showed that the proportion of PD-1 of CD8^high T cells in inactive RA patients was significantly higher than that in active patients and healthy people,and the proportion of PD-1 in,DP T subgroups was also significantly higher than that in active RA patients.9.HBV DNA increased the apoptosis of CD8^high T cells and reduced the apoptosis of CD8^low T and DN T in healthy individuals The apoptosis of T cell subgroups in healthy people was detected by flow cytometry after peripheral blood PBMC was stimulated by HBV DNA for 48 hours.The results showed that apoptosis of CD8^high T cells increased,while that of CD8^low T cells and DN T subgroups decreased.10.HBV DNA combined with IFN-? increased the apoptosis of CD8^high T cells in patients with SLE 48 hours after stimulation of peripheral blood PBMC by HBV DNA and IFN-?,the apoptosis of T cell subgroups in patients with SLE and RA was detected by flow cytometry.The apoptosis of CD3⁺ T,CD4⁺ T and CD8^high T cells is significantly increased in patients with SLE.Conclusion: 1.The infection rate of hepatitis B in patients with RA was significantly higher thanthat in patients with SLE.2.Patients with HBV infection and past infection were mainly distributed in inactiveSLE and active RA patients.3.The level of IFN-? in patients with RA in active stage was significantly higherthan that in inactive stage,and the expression level in patients with RA wassignificantly higher than that in patients with SLE.4.The percentage of CD8^high T cells in patients with active SLE was significantlyhigher than that in patients with active RA.The proportion of CD8^high T cells inpatients with active RA was significantly decreased.5.HBV DNA combined with IFN-? can significantly increase the apoptosis ofCD8high T cells in patients with SLE.