NK细胞及其表面受体在Graves病中作用的研究

发布时间：2018-07-12 10:12

本文选题：NK细胞 + Graves病　；参考：《吉林大学》2016年硕士论文

【摘要】：背景:Graves病(Graves’diseases,GD)是一种器官特异性的自身免疫性疾病,好发于女性,男女比例大约为1:4-6。目前GD病因不清,发病机制复杂而多样,治疗后复发率高,因此对发病机制进行深入研究显得尤为重要。有研究发现,有多种天然免疫参与了自身免疫性疾病的发生、发展。自身免疫性疾病中自身抗体对自身组织的攻击、T细胞对自身正常细胞的杀伤是导致自身组织破坏的重要因素,而天然免疫对适应性免疫具有调控作用,对B细胞的分化、成熟和分泌免疫球蛋白、T细胞的活化和抗原呈递均有有重要作用。研究发现NK细胞活性及其频率在GD患者外周血中明显降低,而且,另有研究发现GD患者在碘131治疗后或甲状腺切除术后NK细胞活性恢复正常。尽管众多研究表明NK细胞在GD的发病中起重要作用,但是具体机制不清。目的:本课题旨在研究成人初发未治疗GD患者中NK细胞数量及其功能的变化,观察其活化性受体与抑制性受体的变化,探讨其在GD发病机制中的作用,为该病的早期诊断、治疗、改善预后、减少复发提供新的思路。资料与方法:本研究选择2012年03月至2014年12月于吉林大学第一医院内分泌科就诊的新发Graves病患者28例,其中男性7例,女性21例,年龄18-58周岁,对照组23例,均来自健康献血者,实验组、对照组均符合研究人群的纳入排除标准。对全部研究对象采血10ml,要求清晨空腹静脉血。检测GD患者和健康人外周血中NK细胞及其表面受体的表达,以及其分泌与杀伤功能的测定,并分析其与临床指标之间的关系。结果:1、相较于正常人,GD患者外周血中CD3-CD56+NK细胞(p=0.0107)、CD3-CD16+NK细胞(p=0.0067)、CD3+CD56+NKT细胞(p=0.0017)、CD3+CD16+NKT细胞(p=0.0012)数量明显降低。2、相较于正常对照组,在GD患者外周血中NKG2D+(p=0.0099)、NKG2C+(p=0.0120)、NKG2A+(p0.0001)、NKp30+(p=0.0114)NK细胞亚群的数量明显减少,而KIR3DL1+(p=0.0119)NK细胞显著增加。同时发现NKp44+、NKp46+、KIR2DL3+、CD158a+、CD158b+等NK细胞亚群的细胞数量与正常对照组无显著差异(p0.05).3、相较于正常对照组,GD患者活化后的NK细胞中CD107a+(p=0.0278)和IFN-?-secreting NK细胞(p0.0001)显著减少。但是未刺激的NK细胞中CD107a+(p=0.0278)和IFN-?-secreting NK细胞与正常对照组无差异表达。4、GD患者外周血中的CD3-CD56+NK细胞(p=0.0481 r=0.3768)、CD3-CD16+NK细胞(p=0.0086 r=0.4870)及NKG2D+NK细胞(p=0.0039 r=0.5275)与患者血中的FT4水平呈负相关。而KIR3DL1+NK细胞(p=0.0028 r=0.5439)则与血中的FT4水平呈正相关.5、NKG2A+NK的数量与GD患者血清中的TRAb水平呈负相关(p=0.0220r=0.4311)。而KIR3DL1+NK细胞的数量与GD患者血清中A-TPO的水平呈正相关(p=0.0037 r=0.5302)。结论:1.在GD患者外周血中NK细胞数量减少,杀伤功能与分泌功能同时受损。2.在GD患者外周血中NK细胞表面活化受体NKG2D、NKG2C、NKp30的数量明显减少。3.在GD患者外周血中NK细胞表面抑制性受体KIR3DL 1数量明显增加。4.GD患者外周血中的NK细胞与血中的FT4水平呈负相关。5.GD患者NKG2A+NK的数量与血清中的TRAb水平呈负相关。
[Abstract]:Background: Graves's disease (Graves' diseases, GD) is an organ specific autoimmune disease, which is a specific autoimmune disease. The proportion of men and women is about 1:4-6. at present, the etiology of GD is not clear, the pathogenesis is complex and varied, and the recurrence rate is high after treatment. Therefore, it is particularly important to study the mechanism of the disease. With the occurrence and development of autoimmune diseases, the attack of autoantibodies to their own tissues in autoimmune diseases, the killing of T cells to their own normal cells is an important factor leading to the destruction of their own tissues, while natural immunity regulates the adaptive immunity, the differentiation of B cells, the maturation and secretion of immunoglobulin, and T cells Activation and antigen presentation have important effects. The study found that NK cell activity and its frequency decreased significantly in peripheral blood of patients with GD, and other studies have found that NK cell activity in GD patients after iodine 131 treatment or after thyroidectomy was restored to normal. Although numerous studies have shown that NK cells play an important role in the pathogenesis of GD, the specific machine is specific. Objective: the purpose of this study is to study the changes in the number and function of NK cells in the primary untreated GD patients, observe the changes in the active receptor and the inhibitory receptor, explore the role of the cells in the pathogenesis of GD, and provide new ideas for the early diagnosis, treatment, prognosis and reduction of the recurrence of the disease. 28 cases of newly diagnosed Graves disease in Department of endocrinology of No.1 Hospital of Jilin University from 03 months to December 2014 2012 were selected, including 7 male, 21 female, 18-58 years old and 23 control group, all from healthy blood donors, experimental group and control group which were in accordance with the exclusion criteria of the study population. All the subjects were collected for 10ml. The expression of NK cells and their surface receptors in peripheral blood of GD and healthy people, and the determination of their secretion and killing function were measured and the relationship between them and clinical indexes was analyzed. Results: 1, compared to normal people, CD3-CD56+NK cells (P =0.0107), CD3-CD16+NK cells (p=0.0067), CD3+CD56+NKT cells in peripheral blood of GD patients (p=0.0067), CD3+CD56+NKT cells (p=0.0067), CD3+CD56+NKT cells (p=0.0067), and CD3+CD56+NKT cells ( P=0.0017), the number of CD3+CD16+NKT cells (p=0.0012) decreased significantly, compared with the normal control group, the number of NKG2D+ (p=0.0099), NKG2C+ (p=0.0120), NKG2A+ (P0.0001) in the peripheral blood of patients with GD decreased significantly, while the number of.2 cells increased significantly. There was no significant difference between the number of NK cell subsets of b+ and the normal control group (P0.05).3. Compared with the normal control group, the CD107a+ (p=0.0278) and IFN- -secreting NK cells (P0.0001) in the NK cells activated by GD patients decreased significantly. The expression of CD3-CD56+NK cells (p=0.0481 r=0.3768), CD3-CD16+NK cells (p=0.0086 r=0.4870) and NKG2D+NK cells (p=0.0039 r=0.5275) in the peripheral blood of patients with GD were negatively correlated with the level of FT4 in the blood, while the number of CD3-CD56+NK cells was positively correlated with the level of blood. The level of RAb was negatively correlated (p=0.0220r=0.4311). The number of KIR3DL1+NK cells was positively correlated with the level of A-TPO in the serum of GD patients (p=0.0037 r=0.5302). Conclusion: 1. the number of NK cells in the peripheral blood of GD patients is reduced, and the damage and secretion function are simultaneously impaired, and.2. is activated by the receptor on the surface of NK cells in the peripheral blood of GD patients. The number of.3. in the peripheral blood of GD patients significantly decreased the number of NK cell surface inhibitory receptor KIR3DL 1 in the peripheral blood of patients with.4.GD. The number of NK cells in the peripheral blood of patients with.4.GD was negatively correlated with the level of FT4 in the blood. The number of NKG2A+NK in patients with.5.GD was negatively correlated with the level of TRAb in the serum.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R581

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