| BackgroundInfection is one of the common complications in patients with autoimmune diseases,which affects the treatment and prognosis.Due to the immune dysfunction of the disease itself and the use of glucocorticoids/immunosuppressants,patients with autoimmune diseases have an increased risk of opportunistic infection,including active cytomegalovirus(CMV).Previous studies have found that systemic lupus erythematosus(SLE)is a high-risk autoimmune disease with active CMV infection,and CMV infection is closely related to the occurrence and development of SLE.At present,the data about the clinical characteristics and risk factors of SLE complicated with active CMV infection was still limited.T cell immunity is very important for the control of CMV infection.Using T-SPOT.CMV to detect the frequency of IFN-y secreting T cells stimulated by CMV-specific IE-1 antigen and pp65 antigen in peripheral blood is helpful to predict the risk of active CMV infection.However,the existing research objects are mainly limited to transplant recipients.Patients with autoimmune diseases have a high incidence of active CMV infection,but the CMV antigen-specific T cell immune response of this population is still blank in the world.Aims1.To analyze the clinical characteristics and risk factors of SLE complicated with active CMV infection.2.To evaluate the CMV antigen-specific T cell immune response in autoimmune diseases with different CMV infection states,and the possible influencing factors of T-SPOT.CMV were further analyzed.MethodsPart 1:The clinical characteristics and risk factors of SLE complicated with active CMV infectionRetrospectively collected the clinical data of patients who were diagnosed with SLE at discharge from the Department of rheumatology in Peking Union Medical Hospital from July 1,2017 to April 1,2019.Patients with CMV DNA or pp65 antigen test results were included and the clinical characteristics and risk factors of SLE complicated with active CMV infection were analyzed.Part 2:The CMV antigen-specific T cell immune response in patients with autoimmune diseasesPatients with autoimmune diseases in Peking Union Medical College Hospital from May 1,2017 to April 26,2020 were selected,and health care workers were included in the same period.The examination of CMV DNA,pp65 antigen,CMV IgM and CMV IgG were supplemented and performed.According to the results of CMV related examination,the patients were divided into latent CMV infection group and active CMV infection group.T-SPOT.CMV method was used to evaluate the CMV antigen-specific T cell immune response in different CMV infection states,and the possible influencing factors of T-SPOT.CMV were further analyzed.ResultsPart 1:The clinical characteristics and risk factors of SLE complicated with active CMV infection1.Finally 231 SLE patients were included in our study,and 115 cases(49.8%)were diagnosed with active CMV infection.78 cases(67.8%)were asymptomic CMV infection and 37 cases(32.2%)were diagnosed as CMV disease.Among the patients with CMV disease,25 patients(67.6%)had fever and/or hemocytopenia,14 cases(37.8%)had CMV hepatitis,2 cases(5.4%)had CMV pneumonia,and 1 case(2.7%)had CMV gastritis.2.After about 1 month's follow-up,in 80 patients with antiviral therapy,the negative conversion rates of CMV DNA and pp65 antigen test were 67.6%and 22%,respectively.In 35 patients without antiviral treatment,the negative conversion rates of CMV DNA and pp65 antigen test were 33.3%and 9.4%,respectively.No CMV disease occurred in 78 patients with asymptomic CMV infection,no matter whether they received antiviral treatment or not.37 patients with CMV disease were improved after antiviral treatment.3.Multivariate analysis showed that presence of other infections(OR=8.003,95%CI=2.108-30.383,p=0.002),methylprednisolone pulse therapy plus immunosuppressants(OR=10.336,95%CI=2.107-50.711,p=0.002)and serum ALB?30g/L(OR=3.367,95%CI=1.15 7-9.796,p=0.026)were independent risk factors for SLE patients with active CMV infection.Part 2:The CMV antigen-specific T cell immune response in patients with autoimmune diseasesIn our study,finally 20 patients with latent CMV infection and 20 patients with active CMV infection were included.In patients with autoimmune diseases:1.The frequency of T cells secreting IFN-y stimulated by IE-1 antigen in active CMV infection group was significantly lower than that in latent CMV infection group[41(IQR 10-66)vs.70(IQR 30-208)SFCs/2.5*105 PBMCs,p=0.033].2.The frequency of T cells secreting IFN-y stimulated by pp65 antigen in active CMV infection group was significantly lower than that in latent CMV infection group[103(IQR 50-322)vs.333(IQR 170-497)SFCs/2.5*105 PBMCs,p=0.018].3.The frequency of T cells secreting IFN-y stimulated by IE-1 and pp65 antigen in active CMV infection group was significantly lower than that in latent CMV infection group[149(IQR 105-420)vs.504(IQR 212-671)SFCs/2.5*105 PBMCs,p=0.007].4.The frequency of T cells secreting IFN-y stimulated by pp65 antigen in CMV disease group was significantly lower than that in latent CMV infection group[75(IQR 58-112)vs.333(IQR 170-497)SFCs/2.5*105 PBMCs,p=0.007].5.The frequency of T cells secreting IFN-y stimulated by IE-1 and pp65 antigen in CMV disease group was significantly lower than that in latent CMV infection group[137(IQR 81-150)vs.504(IQR 212-671)SFCs/2.5*105 PBMCs,p=0.006].6.The frequency of T cells secreting IFN-y stimulated by pp65 antigen in the strong immunosuppressive therapy group was lower than that in the weak immunosuppressive therapy group[58(IQR 18-95)vs.302(IQR 75-398)SFCs/2.5*105 PBMCs,p=0.081].Conclusions1.Presence of other infections,recent methylprednisolone pulse therapy plus immunosuppressants,serum ALB?30 g/L can increase the risk of active CMV infection in patients with SLE.2.In patients with autoimmune diseases,the CMV antigen-specific T cell immune response in patients with active CMV infection and CMV disease was significantly lower than that in patients with latent CMV infection.Immunosuppressive therapy may affect CMV-specific T cell immune response. |
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