HLAⅡ类基因与安徽地区汉族人群玫瑰糠疹的相关性研究

发布时间：2018-05-20 12:58

  本文选题：HLA等位基因 + 玫瑰糠疹　； 参考：《安徽医科大学》2017年硕士论文

【摘要】：研究背景玫瑰糠疹是一种急性炎症性皮肤病,1860年由Gilbert首次报道,全世界各地均有发病。皮损表现为躯干部及四肢近端泛发椭圆形红色斑丘疹、斑疹及斑片,呈圣诞树样分布,好发于10-35岁的青少年及青壮年,病程通常持续2-3个月。关于玫瑰糠疹的病因及发病机制,目前尚未阐明。病毒感染学说以及细胞介导的免疫学说受到十分关注。病毒感染学说认为,人类疱疹病毒6型和7型(HHV-6、HHV-7)与玫瑰糠疹的发病密切相关。而免疫学说提出,玫瑰糠疹是一种细胞介导的免疫性疾病。1985年,Aiba和Tagami进行玫瑰糠疹的组织病理学检查,结果显示,表皮内单一核细胞浸润,真皮浅层血管周大量辅助性T淋巴细胞浸润,朗格汉斯细胞增多。此外,这些细胞及角质形成细胞表面有HLA-DR抗原的表达。Yoshiike等研究发现,在玫瑰糠疹患者外周血中T淋巴细胞表面HLA-DR抗原的表达增多,但随着疾病的恢复,其表达逐渐下降直至恢复正常。Sugiura等研究显示,玫瑰糠疹患者皮损中CD1a+细胞、浸润淋巴细胞的数目以及CD4+/CD8+浸润细胞比例的变化都与疾病的阶段及皮损的严重程度呈正相关。Neoh等研究显示,玫瑰糠疹患者皮损中朗格汉斯细胞、CD4+/CD8+浸润细胞比例增加,没有检测到活性B细胞和NK细胞。Gangemi等和Drago等分别对玫瑰糠疹患者进行血清细胞因子检测研究,结果发现患者血清中趋化因子、IL-22、IL-17、IFN-γ、VEGF及IP-10水平升高。然而我们既往研究发现玫瑰糠患者血清中IFN-γ水平降低。关于玫瑰糠疹与HLA等位基因及单倍型之间相关性研究甚少。2006年Miranda等对30例非裔巴西玫瑰糠疹患者和45例正常对照进行HLA等位基因检测,结果发现HLA-DQB1*04(RR=4.00,95%CI=1.20 13.28,P=0.018)在病例组的阳性率(33.3%)明显高于正常对照(11.1%),表明HLA-DQB1*04与巴西玫瑰糠疹的发病相关。目前尚未有关于中国人玫瑰糠疹与HLA等位基因及单倍型之间的相关性研究。研究目的该课题旨在探讨HLA-Ⅱ类基因与玫瑰糠疹之间的相关性,证实玫瑰糠疹的免疫学发病机制。实验材料与方法采用病例-对照研究,收集55例玫瑰糠疹患者和90例正常对照血样,提取DNA,应用直接测序法(PCR-SBT)进行HLA-DRB1基因分型,应用序列特异性引物-多聚酶链反应法(PCR-SSP)进行HLA-DQA1及HLA-DQB1基因分型,采用卡方检验分析这些等位基因频率在玫瑰糠疹和正常对照之间有无差异。结果结果发现,HLA-DQB1*03:03在玫瑰糠疹患者中的频率明显高于正常对照组(47.27%vs 21.11%,P=0.001;RR=2.239;95%CI:1.376-3.645)。结论研究表明,免疫系统参与玫瑰糠疹的发病过程。HLA-DQB1*03:03可能是玫瑰糠疹发病的危险因素。
[Abstract]:Background pityriasis roseus is an acute inflammatory skin disease first reported by Gilbert in 1860. The lesions were characterized by extensive oval red macular papules, macules and patches at the proximal end of the trunk and extremities, with a Christmas tree distribution. The lesions were likely to occur in adolescents and young adults aged 10-35 years. The course of disease usually lasted for 2-3 months. The etiology and pathogenesis of pityriasis roseus have not been elucidated. The theory of viral infection and cellular mediated immunity have attracted much attention. According to the theory of virus infection, HHV-6 and HHV-7 of human herpesvirus 6 and 7 are closely related to the pathogenesis of pityriasis roseus. The immunological theory suggests that pityriasis roseus is a cell-mediated immune disease. Histopathological examination of pityriasis roseus was carried out in 1985 by Aiba and Tagami, and the results showed that mononuclear cells infiltrate in the epidermis. A large number of helper T lymphocytes infiltrated around the superficial dermis and Langerhans cells increased. In addition, the expression of HLA-DR antigen on the surface of these cells and keratinocytes. Yoshiike and so on, found that the expression of HLA-DR antigen on T lymphocytes in peripheral blood of patients with pityriasis roseus increased, but with the recovery of disease, Studies showed that the expression of CD1a cells in skin lesions of pityriasis roseus patients gradually decreased until they returned to normal. The number of infiltrating lymphocytes and the percentage of CD4 / CD8 infiltrating cells were positively correlated with the stage of disease and the severity of lesions. Neoh and other studies showed that the percentage of Langerhans cell CD4 / CD8 infiltrating cells in skin lesions of patients with pityriasis roseus increased. No active B cells, NK cells, Gangemi and Drago were detected in serum cytokines in patients with pityriasis roseus. The results showed that the levels of IL-22, IL-17, IFN- 纬 and IP-10 in serum of patients with pityriasis roseus were higher than those of patients with pityriasis roseus. However, our previous studies have found a decrease in serum IFN- 纬 levels in patients with rose chaff. There was little correlation between pityriasis roseus and HLA allele and haplotype. In 2006, Miranda et al detected HLA alleles in 30 African-American patients with pityriasis roseus and 45 normal controls. The results showed that the positive rate of HLA-DQB1O04RRR 4.00 ~ 95) in the case group was significantly higher than that in the normal control group, indicating that HLA-DQB1*04 was related to the occurrence of pityriasis roseus. There is no study on the association between pityriasis roseus and HLA alleles and haplotypes in Chinese. Objective to investigate the relationship between HLA- 鈪，

本文编号：1914712