Relationship between Systemic Lupus Erythematosus and Cytomegalovirus Infection

With the in-depth study of the pathogenesis of systemic lupus erythema-tosus (SLE), the intervention of new immunosuppressive agents and biological agents, the prognosis of SLE is significantly improved compared with the past, but some SLE patients still have no effect on conventional treatment. Good, the condition has not healed. After induction of high-dose glucocorticoids >1mg/(kg·d) or ≥1 cytotoxic drugs, the clinical and experimental indicators continue to be unresolved or even worsened as refractory systemic lupus (refractorysystemic lupus) Erythematosus, RSLE). Cytomegalovirus (CMV) belongs to herpesvirus β subfamily and is a double-stranded DNA virus. The number of CMV-infected people in China is increasing year by year. The clinical manifestations of CMV active infection and systemic damage caused by RSLE are difficult to identify, and are often mistaken for disease. Activities, and blindly using large doses of hormones and immunosuppressive agents, the patient’s condition is further aggravated, and even lead to death. In this study, 45 patients with RSLE underwent laboratory tests such as CMV-DNA and T lymphocyte subsets, and analyzed the correlation between CMV-DNA load and CMV-positive RSLE laboratory test indicators, and compared CMV-positive RSLE and CMV-negative RSLE patients. Clinical features, to explore the relationship between CMV infection and RSLE, in order to improve the efficacy of RSLE.

1. Materials and Methods of SLE and CMV experiment

1.1 Materials

The selected 45 patients with RSLE were from the outpatient and inpatients of Pingxiang People’s Hospital, all of whom were women, with an average age of (45.26±10.87) years. According to the results of CMV test, 45 patients with RSLE were divided into CMV positive RSLE group and CMV negative RSLE group, 38 cases and 7 cases respectively. Forty-six healthy physical examinations in the hospital were set as normal control group, including 10 males and 36 females, with an average age of (42.34±8.65) years old. All patients underwent SLEDAI-2000 scoring, comprehensive medical history collection and physical examination, paying special attention to the symptoms and signs of CMV disease, including hyperthermia, lymphadenopathy, splenomegaly. 45 patients with RSLE met the following criteria: 1 met American rheumatoid disease Association revised SLE diagnostic criteria in 2009; 2 lupus nephritis (LN), urine protein quantitation (24h) ≥ 500mg / 24h; 3 prednisone (Pre) maintenance amount ≥ 10mg / L; 4 cyclophosphamide (CTX ), cumulative use of 6 ~ 8g is invalid, or other immunosuppressive agents (cyclosporine A, azathioprine, enzymatic phenolate, etc.) for 3 months is invalid; 5 patients with end-stage organ failure.

1.2 Method adoption

Beckman Counter Cytomics FC500 flow cytometry detects T lymphocyte subsets. The kit was purchased from Beckman Counter. The flow cytometry calibration and compensation settings were performed using a series of tuned microspheres and reagents from the flow cytometry system. Sysmex 4000i blood cell analyzer for lymphocyte count; ABI 7300 quantitative PCR instrument for detection of CMV-DNA, reagent purchased from Sun Yat-sen University Daan Gene Co., Ltd.; AU5800 automatic biochemical analyzer for 24h urine protein and CRP, reagent purchased from Beijing Li Deman Biochemical Co., Ltd.; Beckman Coulter IMMAGE800 specific protein analyzer detects complement C3, C4, and the kit was purchased from Beckman Counter. All tests were performed in strict accordance with the kit instructions.

1.3 Statistical processing

Using SPSS18.0 statistical software, the measurement data were expressed as (x±s), and the t-test was used for comparison between groups; the count data was expressed by the number of cases and the percentage, and the chi-square test was used for comparison between groups, using two-tailed Spearman rank correlation for two The correlation between the variables was analyzed, and P < 0.05 was considered statistically significant.

2. Results of SLE and CMV experiment

2.1 CMV-DNA

Correlation between clinical load and clinical characteristics of CMV-positive RSLE patients. CMV-DNA load and CMV-positive RSLE patients with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), urine protein quantitation (24h), SLE disease activity index (SLEDAI ) was positively correlated with body temperature (r=0.509, 0.241, 0.353, 0.365, 0.249; both P<0.05), and negatively correlated with complement C3 level (r=0.249, P=0.035<0.05).

2.2 CMV positive

The clinical characteristics of RSLE group and CMV negative RSLE group and normal control group were significantly higher than those of normal control group (3/46, 6.52%, P<0.01). The ESR, urine protein quantitation (24h) and SLEDAI were significantly higher in the CMV-positive RSLE group than in the CMV-negative RSLE group (t= 9.35, 7.65, 5.98; P<0.05), and the complement C3 level was significantly lower than the CMV-negative RSLE group. (t = 3.28, P<0.05), ESR in 24 patients with CMV-positive and CMV-negative RSLE were significantly higher than those in the normal control group (P<0.05), and the level of complement C3 was significantly lower than that in the normal control group (P<0.05). . The incidence of fever, lymphadenopathy, splenomegaly and hormonal resistance in the CMV-positive RSL group was higher than that in the CMV-negative RSLE group (F=14.22, 10.35, 17.24; P<0.05).

2.3 CMV

The lymphocyte subsets of the positive RSLE group and the CMV-negative RSLE group and the normal control group are shown in Table 1. The CD3+, CD4+, CD8+ T lymphocytes and total lymphocyte counts in the CMV-positive RSLE group were significantly higher than those in the CMV-negative RSLE group (t = 6.32, 6.04, 5.42, 7.62; both P < 0.05) and the normal control group (t = 10.41, 12.32, 6.32, 7.89; all P<0.01), CD4+/CD8+ was significantly lower than CMV negative RSLE group (t=4.56, P<0.05) and normal control group (t=5.02, P<0.05). There was no significant difference in the above data between the CMV-negative RSLE group and the normal control group.

3. Conclusion of SLE and CMV experiment

The disease activity index of the LE group was significantly higher than that of the CMV negative RSLE group. The incidence of fever, lymphadenopathy, splenomegaly and hormonal resistance in the CMV-positive RSLE group was higher than that in the CMV-negative RSLE group. It is suggested that CMV infection may cause aggravation of RSLE patients and even hormone resistance. Wang Rong and other studies showed that the CD38/CD3 molecular level was significantly higher than that of the healthy control group, and it was positively correlated with disease activity, indicating that the peripheral blood activated T lymphocytes increased in SLE patients. Liu Cuijie and other research results show that the level of CD38/CD3 in peripheral blood lymphocytes of patients with active SLE is significantly increased, thus inducing a large number of autoantibodies. This study found that CD3+, CD4+, CD8+ lymphocytes and total lymphocyte counts in the CMV-positive RSLE group were significantly higher than those in the CMV-negative RSLE group and the normal control group, and CD4+/CD8+ was significantly lower than the CMV-negative RSLE group and the normal control group. Consistent. Therefore, this study suggests that CMV infection can activate T lymphocytes in patients with SLE, promote the production of a large number of antibodies in B lymphocytes, and worsen the patient’s condition, which is one of the causes of refractory SLE patients.

Deng Xiaoli et al. Follow-up study of patients with systemic lupus erythematosus complicated with active cytomegalovirus infection found that antiviral therapy had no effect on disease activity in SLE patients. In this study, 2 patients with CMV-positive RSLE after ganciclovir treatment found that the conventional dose of hormone after antiviral treatment can better control the disease. Therefore, patients with SLE who have been treated with hormones or immunosuppressive agents for a long time should be routinely tested for serum or urine CMV virus, and targeted therapy to improve efficacy. Due to the patient’s fluidity and informational conditions, only 2 patients with CMV-positive RSLE were followed up for antiviral therapy. Therefore, the efficacy of antiviral therapy in patients with CMV-positive RSLE is worthy of further investigation.