CMV infection is one of the most common opportunistic infections in patients with autoimmune diseases. The clinical manifestations of CMV infection are diverse, ranging from viral syndromes such as fever and hemocytopenia to tissue and organ damage of lung, gastrointestinal tract, liver, eyes or other organs. CMV infection can mimic the clinical manifestations of autoimmune diseases, thereby affecting the clinicians’ judgment of the disease, bringing greater difficulties to treatment, and severely affecting the prognosis of patients [4, 22, 23]. At present, more and more attention is paid on the screening of CMV infection in patients with autoimmune diseases.
Currently, research on the application of monitoring CMV antigen-specific T cell immunity is mainly implemented in patients with solid organ transplantation and hematopoietic stem cell transplantation. Studies have demonstrated that low CMV antigen-specific T cell immune response was associated with high risk of active CMV infection or CMV disease. Monitoring of CMV specific T cell immunity can assist in predicting the risk of CMV replication and progression to CMV disease, and guide the duration of preventive anti-CMV therapy. This in turn helps in reducing the duration and intensity of CMV monitoring as well as the high cost associated with anti CMV treatment and drug side effects (such as nephrotoxicity, bone marrow suppression, etc.) in patients with low risk of CMV infection [24]. The CMV antigen-specific T cell immune response in patients with autoimmune diseases which are considered as a common immunosuppressive population, still remained to be unclear. The main purpose of this study is useing T-SPOT.CMV method to evaluate the CMV antigen-specific T cell immune response in different CMV infection states, and to analyze the possible factors that affect the CMV antigen-specific T cell immune response in patients with autoimmune diseases
This study found that the frequency of IFN-γ-secreting T-cells stimulated by IE-1, pp65 and IE-1 & pp65 in patients with autoimmune diseases complicated with active CMV infection was significantly lower than those with autoimmune diseases complicated with latent CMV infection, and in patients with autoimmune diseases complicated with CMV disease was significantly lower than those with autoimmune diseases complicated with latent CMV infection. The results of the previous studies with regard to solid organ transplantation and hematopoietic stem cell transplantation recipients have shown that under the occurrence of CMV viremia or active CMV infection including CMV viremia and CMV disease, CMV antigen-specific T cell immune response stimulated by IE-1 and/or pp65 antigen was significantly lower than that of latent CMV infected patients before and after transplantation. This suggested that low CMV antigen-specific T cell immune response is related to the occurrence of active CMV infection [12, 15, 25-27]. In the prospective study conducted on dynamic monitoring of CMV antigen-specific T cell immune response in solid organ transplantation and hematopoietic stem cell transplantation recipients, the frequency of IFN-γ-secreting T-cells stimulated by pp65 and IE-1 showed no change or increase in latent CMV infected patients before and after transplantation, while the frequency of IFN-γ-secreting T cells stimulated by pp65 and IE-1 antigens was significantly reduced in active CMV infected patients [13, 14], suggesting that the occurrence of active CMV infection might be related to insufficient T cell immune response to CMV. This study illuminated that in autoimmune patients, the CMV antigen-specific T cell immune response of active CMV infection and CMV disease was lower than that of latent CMV infection, and this was consistent with that of the researches conducted in transplant patients.
T lymphocytes play an important role in the initiation and continuation of immune mechanism, and are considered as the body's main defensive cells against pathogens. Previous studies have found that 70%-80% of circulatory lymphocytes come from T lymphocytes, and the reduction in the number of circulatory lymphocytes affects the body's normal immune defense function [28]. For viral infections, CD8+ T cells are shown to be as the main effector cells, and CD4+ T cells play an important role in establishing the body’s long-term immune control of CMV infection. CD4 + T cells and CD8 + T cells play a synergistic role in the process of CMV infection control. Qin et al[29]. have analyzed the relationship between lymphocyte subsets and CMV infection status in 125 SLE patients, and the results showed that the lymphocytes, CD4+ T cell and CD8+ T cell count in the CMV disease group were significantly lower in the CMV viremia group and the inactive CMV infection group, but there was no significant difference in the CMV viremia group and the inactive CMV infection group. This indicated that the decrease of lymphocytes, CD4+T cell and CD8+T cell count might be related to the occurrence of CMV disease [29]. Similar to the results of the study by Qin, this study also showed that the lymphocyte count of CMV disease patients was significantly lower than that of subclinical CMV infection group and latent CMV infection group, but there was no significant difference between subclinical CMV infection group and latent CMV infection group, confirming that the decrease in lymphocyte count might be related to the occurrence of CMV disease. However, there was no significant difference in the number of CD4+T cells and CD8+T cells among the three groups, and this might be related to the fact that the number of lymphocyte subsets detected in the enrolled patients was less (n = 47). Due to immune dysfunction associated with autoimmune diseases and the application of immunosuppressive therapy, the changes in lymphocyte subsets in this population remained much complicated. With regard to the effect of lymphocyte subsets on CMV antigen-specific T cell immune response, there are currently no studies on this aspect both at home and abroad, and large sample studies are necessary for furtherexploration.
Consistent with the study results of Liu [17], the frequency of IFN-γ-secreting T-cells after stimulation with PP65 was significantly higher than that after stimulation with IE-1 antigen, and the stimulatory effect of PP65 was better than that of IE-1. In addition, this study also found that different lymphocyte levels affected the number of IFN-γ-secreting T-cells after stimulation with PP65, while IE-1 antigen was unaffected by the lymphocyte levels. IE-1 was shown to be more stable and had better effect than pp65.
One of the basic goals of CMV antigen-specific T cell immunosurveillance is to stratify the risk of CMV-related complications (CMV disease) in order to improve the clinical management of patients. This study is first to use the standardized T-SPOT.CMV method to evaluate CMV antigen-specific T cell immune response in patients with autoimmune diseases under different CMV infection conditions in the global. It has an important clinical significance in predicting the value of CMV infection and CMV disease in patients with autoimmune diseases. However, this study also has some limitations. Firstly, although the underlying diseases of all patients are autoimmune diseases that require hormone or immunosuppressive therapy, there are certain similarities in the underlying diseases, leading to differences in the underlying diseases of different groups. Secondly, the small sample size limits the analysis of factors affecting the CMV antigen-specific T cell immune response in patients with autoimmune diseases. Finally, this study cannot infer the causal relationship between CMV antigen-specific T cell immune response and the occurrence of active CMV infection, so the further prospective exploration is warranted in the future.