Clinical Analysis Of Systemic Lupus Erythematous With CMV Infection

BackgroundCytomegalovirus(CMV) infection is one of the most common opportunistic infections in human beings, and has high morbidity and mortality in immunocompromised patients such as patients under glucocorticoid and immunosuppressants, solid organ and bone marrow transplant patients. Systemic lupus erythematous(SLE) patients may be prone to CMV infection because of disordered immune function due to SLE flare and/or long-time use of substantial glucocorticoid and immunosuppressants. Recently, CMV infection is considered can induce or worsen SLE. CMV infection has a close relationship with SLE. Currently, CMV-DNA detection and CMV-pp65antigen assay are considered have good sensitivity and specificity in CMV infection diagnosis, and are used to guide anti-virus treatment. However, in clinical work, we found in the SLE with CMV infection patients, the specificity of CMV-pp65antigen assay isn’t so well. Currently, there are rare studies on comparing CMV-DNA with CMV-pp65on the diagnose and treatment in SLE with CMV infection patients at home and abroad. Lupus nephritis(LN) is the one of the most common and server complication of SLE patients, the wide use of glucocorticoid and immunosuppressants in recent years controls LN very well, however, increases the morbidity and mortality of infection in these patients. A retrospective study found that the major cause of death in SLE had changed to infection from LN20years ago. Lymphocyte (LY) declining can be caused both by LN activity and long-term massive use of glucocorticoid and immunosuppressants, and can lead the patients prone to have infections, conversely, infections and following anti-infection treatments may deteriorate LN or cause more server lymphopenia even lead to death. So, it is very important to surveillance lymphocyte count when treating LN to watch out for infection. There are only few studies on lymphopenia in LN and the its relationship between LN activity, glucocorticiod and immunosuppressants, infection and related anti-infection treatments.Objectives1. Comparing the three CMV-DNA, CMV-pp65and CMV-IgM test in the SLE patients for monitoring the development of CMV disease and evaluating their value in guiding anti-virus therapy;2. Analyzing lymphocyte subsets in the SLE with CMV infection patients;3. Evaluating the safety and effectiveness of the anti-virus treatment in SLE with CMV infection patients;4. Investigating the relationship between LN activity, glucocorticoid and immunosuppressants, infection and following anti-infection treatments and lymphopenia.Materials and MethodsThe study enrolled185SLE with CMV infection patients that were accepted by PUMCH from2011.01to2014.01. We retrospectivlly collected the clinical manifests, complete blood cell counts, CMV-DNA, CMV-IgM, CMV-pp65, lymphocyte subsets, treatment and prognosis.The study also enroll187LN patients which was accepted by PUMCH, with intact clinical and patological data. Patients with malignacy, prengnacy and server malnautrition are ruled out for final analysis. Baseline features, follow-up records, treatment and prognosis were reviwed and analyzed retrospectively.CMV-DNA detection:CMV-DNA was quantified using real-time PCR fluorescence; CMV-pp65antigen assay:CMV-pp65antigen positive polymorphonuclear leukocytes cells (PMNs),which shows well-distributed apple green on the nuclueus, are detected by indirect monoclonal antibody immunofluorescence; CMV-IgM: CMV-IgM was detected by enzyme-linked immunosorbent assay (ELISA).Results1. Comparing the three CMV-DNA, CMV-pp65with CMV-IgM test If use having CMV disease as the standard, the senitivity and specificity of CMV-DNA are66.1%and55.3%, respectively. The area under ROC curve of CMV-DNA is0.629>0.5,P=0.007. The senitivity and specificity of CMV-pp65are87.0%and7.6%, respectively. The area under ROC curve of CMV-pp65is0.431<0.5, P=0.097. The senitivity and specificity of CMV-IgM are55.3%and30.9%, respectively. Comparing CMV-DNA with CMV-pp65, the Kappa value is-0.176(P=0.055)2. Lymphocyte subsets change in SLE with CMV infection patients According to the lymphocyte subsetes analysis, SLE with CMV infection patients shows delicine in lymphocyte (894.76±624.41/μl),B lymphocyte (132.44±118.08/μl),NK cell(31.74±31.04/μl), CD4+lymphocyte(301.41±267.34/μl), and increase in the ratio of CD8+lymphocte (43.91%±14.76%), converse of CD4+/CD8+; raise of the ratio of CD8+CDDR+and CD8+CD38+lymphocyte, which represent CD8+lymphocyte abnormal activation,47.69%±24.89%vs71.75%±16.11%, respectively. The ratio of CD8+lymphocyte abnormal activation is77.5%. Althrough there are no significant statistical difference, we can see in CMV disease patients, the decline of CD4+lymphocyte are more server than asymptomatic CMV infection patients,199.63±179.39vs359.38±288.85/ul respectively. The ratios of CD8+lymphocyte abnormal activation are both very high in CMV disease patients and asymptomatic CMV infection patients,85.7%vs73.1%, respectively, without statistical difference (P=0.348).3. The safety and effectiveness of anti-virus treatment in SLE with CMV infection patients152SLE with CMV infection patients accepted anti-virus treatment, of which63CMV disease patients,61patients’symptom improved, cure rate is96.8%. Among 72CMV-DNA positive patients,54patients CMV-DNA turned to negative after anti-virus therapy,17patients show obvious declines in CMV-DNA copies except1patient, total effective rate is98.61%. Among69CMV-pp65positive patients’s follow-up49.3%(34/69) turned to negative after the treamment, among35patients whose CMV-pp65didn’t turn to negatvie, there were5patients show raise of CMV-pp65positive PMNs(raisel-24positive PMNs).41.7%(15/36) CMV-IgM postitive patients turned to negative after the treatment.13asymptomatic CMV infection patients didn’t accept anti-virus therapy, during follow-up, none of which turn to CMV disease, and one out of these patient’s CMV-pp65declined spontaneously.4. The incidence rate of lymphopenia in LN patients During the time the follow-up,124patients showed lymphopenia (66.3%,124/187), of which29patients showed server lymphopenia (15.5%,29/187),11(5.9%,11/187)patients showed persistent server lymphopenia.5. Patients with persistent server lymphopenia had a high CMV infection morbidity and high death rate.11persistant server patiets all had server infecitons, of which8patients show CMV infection (2.7%,8/11).2of11patients give up treatments because of infectious shock and viral encephalitis,1of11patient died of pulmonary multiple microbial infections. Among enrolled187patients,3patients give up treatments and1died, among these4patients,3are (75%,3/4) persistent server lymphopenia patients.Conclusions1. In the SLE with CMV infection patients, the sensitivity of qualitative CMV-pp65antigen assay result is good, but the specificity is poor; comparing to CMV-pp65and CMV-IgM, CMV-DNA is more useful in diagnose and treatment follow-up of CMV disease in SLE patients.2. Comparing to SLE patients, B lymphocyte declines and CD8+cell abnormal activation is high in SLE with CMV infection patients; monitoring the changes of lymphocte subset is useful for monitoring CMV infection in SLE patients.3. CMV-DNA has the highest recovery rate in anti-CMV treatment follow-up, CMV-pp65recovery rate<50%, CMV-pp65positive cells can declince spontaneously without anti-virus therapy.4. Lymphopenia has a high incidence rate in LN, besides the flare of LN and glucocorticoid and immunosuppressants can casuse lymphopenia, in clinical work, we should be aware of infections and the treatments to infections can also lead to lymphopenia.5. Patients with persistent server lymphopenia have high CMV infection morality and are at high risk of infection and mortality.