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The Clinical Characteristics Of Brucellosis And The Mechanism Of The Action Of Invariant NKT Cells In Brucellosis

Posted on:2021-04-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhouFull Text:PDF
GTID:1364330605955518Subject:Infectious disease science
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Objective: To study the clinical characteristics of brucellosis patients and the mechanism of invariant NKT cells in brucellosis,provided reference for clinical diagnosis and treatment and provided a theoretical basis for immunotherapy.Methods: 1)1542patients were analyzed retrospectively,and the clinical characteristics,laboratory characteristics and treatment prognosis were summarized,For 22 patients with reproductive system damage and 115 children with brucellosis,the clinical characteristics and laboratory tests were summarized respectively;2)Taking the patients with acute and chronic brucellosis and the healthy people as the research objects,the expression level of the invariant NKT cells and their subsets and the correlation with other indexes were analyzed by using the flow cytometry,cytometric bead array and other experimental methods,and observe the relationship between the characteristics of changes and other indicators before treatment,6 weeks and 12 weeks;3)Through in vitro experiments,we revealed the potential mechanism of the involvement of invariant NKT cells in acute Brucella infection.Results: 1)Brucellosis patients were more common in 19-45 years,and occured in May-August.There are differences in clinical characteristics and laboratory indexes between acute and chronic patients.Age?45 years old and ESR increase were independent risk factors for poor prognosis.Testitis was the most common cause of reproductive system damage in men,vaginitis and cervicitis in women.In addition to typical clinical manifestations,weight loss and anorexia were common in children;2)In acute phase,the number of invariant NKT decreased,mainly due to the decrease of CD8+ invariant NKT,CD4-CD8-invariant NKT cells were negatively correlated with ESR.There was no significant difference in IFN-? and IL-4 production between the patients with acute stage and the healthy people.In the acute phase,IFN-?and IL-23 were increased,while in the chronic phase,IL-10 was increased.There was anegative correlation between the expression of IL-10 and invariant NKT cells in patients with acute stage,CD4+invariant NKT cells were negatively correlated with IFN-?.There was a positive correlation between invariant NKT cells and IFN-?,IL-8 and IL-23,CD4-CD8-invariant NKT cells were negatively correlated with IFN-?,IL-6 and IL-8,and positively correlated with TNF-?.The proportion of the invariant NKT cells gradually recovered with the treatment,mainly CD8+invariant NKT cells increased.At 12 weeks of treatment,the recovery level of the proportion of invariant NKT cells in patients over 45 years old was lower than that in patients under 45 years old.IL-6 was positively correlated with CRP,ROC curve showed that the optimal threshold of IL-6 was 62.416ng/l,the area was 0.758(95% CI: 0.564-0.818),the sensitivity and specificity were 54.7% and 86.2%,respectively.IL-6 decreased gradually with the treatment,and there was significant difference in each period,There was significant difference between TNF-? and each phase at 12 weeks of treatment.3)Rhil-21 can inhibit the proliferation of invariant NKT cells by?-Gal Cer.When IL-21 stimulated PBMC in vitro,IL-6,IFN-? and IL-10 were produced.The expression of CCR5 and CCR6 was high in the invariant NKT cells.Conclusions: 1)Brucellosis has different clinical manifestations,we need to pay attention to the clinical characteristics of reproductive system injury and brucellosis in children.For patients without complications,rifampicin combined with doxycycline is needed for 6 weeks,for patients with complications,rifampicin combined with doxycycline is needed for 12weeks;(2)IL-6 can be used as a simple,operable and clinical effects to understand the disease activity of brucellosis;3)The decrease of the proportion of invariant NKT cells in patients with acute stage may be related to the high expression of CCR5 and CCR6.4)The invariant NKT cells are involved in the occurrence and development of brucellosis,and are involved in the cellular immune regulation of Brucella infection.
Keywords/Search Tags:Brucellosis, Reproductive system, Children, Invariant NKT cells
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