| BackgrandVZV(varicella-zoster virus) is a double-stranded DNA in core virus, its diameter is about 100-200 nm, it is shaped of symmetrical polyhedron, and with a layer of membrane outside. VZV is a member of the alpha-herpes virus family, and it is prone to skin cells, nerve cells, CD4 and CD8+T lymphocytes. Naturally, human is the only host of VZV, and all humans are susceptible to VZV, the spread of VZV mainly through the respiratory tract and close contact, which infected with the human body causes vricella and herpes zoster. Varicella (chickenpox) is a primary infection of epithelial cells of the skin during childhood, the main clinical manifestations is the blisterof in whole body and fever. Varicella with high infectious is the world epidemic disease, without protection, the infection of vulnerable groups usually can reach 100%,96% of them showed obvious clinical symptoms, and 4% for the recessive infection. After the recover of varicella, virus can be long-term latent in the dorsal root ganglia or trigeminal ganglion. Under the condition of lower immunity or induced by some factors such as fatigue, cold, drinking, menstruation, illness, etc, the latent virus in ganglion can be reactivated, copy and proliferation, spread along the nerve axons diffusion to the skin, it can lead to ganglia inflammation, necrosis and neuralgia, erythema, blister appeared at the skin of one side of the body, this is defined as herpes zoster. In recent years, since the clinical applications of glucocorticoid and immunosuppressive drugs, the incidence of herpes zoster presents the trend of rising and gradually tend to be younger. The estimated average overall incidence of HZ is about 3.4-4.82 per 1000 person years which increases to more than 11 per 1000 person years in those aged at least 80 years old. And epidemiological studies have shown that in the United States, about 90% of adults are susceptible to herpes zoster, and 30% of them shall suffer from herpes zoster at least once in a lifetime, and this huge medical burden is not allow to ignore.A few days after the onset of rash, blisters of herpers zoster turns to be rupture, dry and scabby, severe lesions and improper cared skin may be formed in the local erosion surface. Generally, course of herpes zoster needs 2-4 weeks, reddish brown spots and pigmentation spots still existed after the recovery, But many older and low immune patients will have more severe nerve pain and the duration is longer. In the original areas there are still persistent intractable pain longer than one month after the vanishing of skin lesions in patients with herpes zoster, which defined as postherpetic neuralgia(PHN), some progression in patients with PHN may be two or three years, even longer, severe nerve pain brought great mental and economic burden to the patient and family.At present, for the diagnosis of herpes zoster, we mostly rely on the physician’s personal experience, but sometimes there will be some other blister diseases, which is difficult to identify with herpes zoster, including pemphigus and bullous pemphigoid, herpes simplex. Therefore, in clinic, some scholars gathers the blister fluid of patients with herpes zoster, to do VZV DNA test for the diagnosis. However, there are some special types of herpes zoster, such as zoster sine herpes, while the patients have obvious neuralgia, and verified by virology experiment VZV exists, but no rash appear or only appear the local skin erythema, couldn’t collect the blister fluid. Therefore, some scholars proposed a new method to detect VZV DNA in peripheral blood from patients. Studies have showed that during the onset of herpes zoster period, the positive rate of VZV DNA test is high in peripheral blood of patients, and VZV is prone to T lymphocytes, in peripheral blood, about 70% VZV exist in peripheral blood mononuclear cell(PBMC), so detecting the VZV DNA in PBMC is more sensitive. Furthermore, compared with the detection of VZV DNA in blister fluid, collecting peripheral blood is easier to quantify, is advantageous to detecte and compare the the level of VZV DNA quantitative under the unified standard, and not easy to pollution.Varicella and herpes zoster both belong to the common clinical disease, but as an important part of VZV pathogenic, the immunity mechanism of VZV infection is still lack of explore. Research shows that the specific immunity of body against VZV is mainly about cell-mediated immunity, T lymphocytes cells are the most important kind of cells in body’s cell-mediated immunity system. In normal state, in order to ensure the normal immune function, the T lymphocyte subgroup maintain a certain balance and interaction with each other, when the abnormal number and functions of T lymphocyte subgroup exist, often leads to the body’s immune function disorder, increase the the chance of virus infection. Researchs are confirmed that T lymphocyte immune response of body play an important role in the process of VZV infection, latent, pathogenic. Compared with the normal, the number of T lymphocyte subsets (CD3+/CD4+/CD8+T lymphocyte) in peripheral blood is obvious changes in patients with herpes zoster. The lack of CD4+T lymphocytes is an important reason for the rash diffusion, prolonged viremia and higher viral DNA copies in patients with varicella and herpes zoster. Domestic and foreign studies have reported that Thl cells and Th2 cells play a regulatory role in the incidence of herpes zoster. Domestic and foreign studies have reported that Thl cells and Th2 cells play a regulatory role in the incidence of herpes zoster, but reports about the role of Thl 7 and Treg cells in herpes zoster is lack of study. Thl 7, Treg cells is independent from Thl and Th2 cells, as unique CD4+T lymphocyte subgroup, the recent study found that Th1 7, Treg cells and their related cytokines play an important role in the pathogenesis of many diseasesin such as autoimmune diseases, infectious diseases and tumor. At the same time, their is an closely contact and a restriction relationship between the two kinds of cells in the differentiation to mature, regulating the function of the immune system. Inducing by cytokine IL-6 and TGF-β1, bring a high expression of transcription factor ROR-yt and STAT-3, initial CD4+T lymphocyte differentiate to Th1 7 cells, secretion of inflammatory factors such as IL-17, mediates the body’s inflammatory response. Inducing by cytokine IL-6 and TGF-Pi, bring a high expression of Foxp3, initial CD4+T lymphocyte differentiate to CD4+CD25+Foxp3+Treg cells, Secrete immune inhibitory cytokines such as IL-10, TGF-β1, plays a role in maintaining the body’s immune balance.In conclusion, herpes zoster and PHN caused a certain psychological and economic burden to patients and their families, there have been evidence that immune suppression phenomenon exists in patients with herpes zoster and PHN patient specific. In clinic, commonly used the percentage of CD4+T and CD8+T lymphocyte subgroupas as the immune indexes to value severity herpes zoster and PHN. However, CD4+T and CD8+T lymphocytes respectively consists of several different functions of cells, therefore, T lymphocyte subgroup does not appropriate to be indicators reflect the body’s specific immune function. In clinical practice, we need to explore the new accurate, simple and effective immune indexes to the severity evaluation and prognosis of patients with herpes zoster and PHN. Since Th17,Treg cells and their related cytokines play an important role in maintaining the body’s immune balance, Further analyzing the relationship between the number and dysfunction of Th17, Treg cells with the incidenceof herpes zoster, disease severity, VZV DNA copies and the development of subsequent PHN, will provide a laboratory basis to the immune detection of Th17 and Treg cells applying to clinical, and provide new ideas to the immune treatment of herpes zoster and PHN.ObjectiveTo investigate the expression of Th17 cells and CD4+CD25+Foxp3+Treg and their related cytokines (IL-6. IL-10, TGF-β1)in patients with herpes zoster before and after treatment. And analyse the relationship between these expression with the patients’clinical characteristics, VZV DNA copies and the development of subsequent PHN. In order to explor the role of Th17 and CD4+CD25+Foxp3+Treg in the patients with herpes zoster. Improve the immune theory to the pathogenesis of herpes zoster, provide laboratory basis for guiding clinical work, and provide new immune treatment of herpes zoster.Method1. Select the 43 patients with herpes zoster who are hospitalized between November 2014 and June 2015,30 cases of healthy adults as normal control. Their venous blood was collected before and 7 days later after treatment. The frequencies of Th17 Cells and Treg cells were detected by flowcytometry, and enzyme-linkedimmuno sorbent assay (ELISA) was applied in serum IL-17, IL-6, TGF-β1 levels. Using SPSS 20.0 software for statistical analysis to investigate their change in patients with herpes zoster before and after treatment.2. Before treatment, according to the clinical characteristics, patients with herpes zoster were divided into two different patient groups (mild or moderate group and severe group); test the VZV DNA copies in peripheral blood lymphocyte; and followed up by PHN for 1 months after the fade of rash, patients were divided into different groups (PHN group and non-PHN group). Using SPSS 20.0 software to analyze the relationship between the expression of Th17, Treg cells and their related cytokines with the patients’clinical characteristics, VZV DNA copies and the development of subsequent PHN.Result1. Frequencies of Th17 and Treg cells in patients with herpes zoster (piror to treatment group and post-treatment group) were significantly higher than in those healthy controls (p<0.05), and frequencies in the piror to treatment group were significantly higher than in the post-treatment group (p<0.05). The piror to treatment group and posttreatment group had much higher serum IL-17 levels than the control group (p<0.05), and the difference between piror to treatment group and post-treatment group had statistical significance (p<0.05). The piror to treatment group had much higher serum IL-6, TGF-β1 levels than the post-treatment group and control group (p<0.05), while the difference between post-treatment group and contral group had no statistical significance.(p>0.05).2. The mean expression of Thl7, Treg cells and their related cytokines was significantly increased in the severe group as compared with the mild or moderate group, and normal controls (p<0.05). The levels of Th17, Treg cells proportion and their related cytokineand in patients with herpes zoster were positively correlated to the VZV DNA copy numbers in patients’peripheral blood (p<0.05). The proportion of Th17, Treg cells and their related cytokines was significantly increased in the PHN group as compared with patients without PHN and normal controls(p<0.05).Conclusion1. The change of Th17 and Treg cells and their related cytokines exist in patients with herpes zoster, and the changement reduce after treatment, so it may play a potential roal in the onset and development of herpes zoster.2. There is a close correlation between the expression of Th17, Treg cells and their related cytokines in patients with herpes zoster with the patients’clinical characteristics, VZV DNA copies and the development of subsequent PHN. After further research, explore the change of number and functions about Th17 and Treg cells in virus infectious diseases, will provide theoretical basis for new clinical antivirus solutions and using protective cell-mediated immunity in the clinic. |
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