HLAⅡ類基因與安徽地區(qū)漢族人群玫瑰糠疹的相關性研究
發(fā)布時間:2018-05-20 12:58
本文選題:HLA等位基因 + 玫瑰糠疹。 參考:《安徽醫(yī)科大學》2017年碩士論文
【摘要】:研究背景玫瑰糠疹是一種急性炎癥性皮膚病,1860年由Gilbert首次報道,全世界各地均有發(fā)病。皮損表現(xiàn)為軀干部及四肢近端泛發(fā)橢圓形紅色斑丘疹、斑疹及斑片,呈圣誕樹樣分布,好發(fā)于10-35歲的青少年及青壯年,病程通常持續(xù)2-3個月。關于玫瑰糠疹的病因及發(fā)病機制,目前尚未闡明。病毒感染學說以及細胞介導的免疫學說受到十分關注。病毒感染學說認為,人類皰疹病毒6型和7型(HHV-6、HHV-7)與玫瑰糠疹的發(fā)病密切相關。而免疫學說提出,玫瑰糠疹是一種細胞介導的免疫性疾病。1985年,Aiba和Tagami進行玫瑰糠疹的組織病理學檢查,結果顯示,表皮內(nèi)單一核細胞浸潤,真皮淺層血管周大量輔助性T淋巴細胞浸潤,朗格漢斯細胞增多。此外,這些細胞及角質(zhì)形成細胞表面有HLA-DR抗原的表達。Yoshiike等研究發(fā)現(xiàn),在玫瑰糠疹患者外周血中T淋巴細胞表面HLA-DR抗原的表達增多,但隨著疾病的恢復,其表達逐漸下降直至恢復正常。Sugiura等研究顯示,玫瑰糠疹患者皮損中CD1a+細胞、浸潤淋巴細胞的數(shù)目以及CD4+/CD8+浸潤細胞比例的變化都與疾病的階段及皮損的嚴重程度呈正相關。Neoh等研究顯示,玫瑰糠疹患者皮損中朗格漢斯細胞、CD4+/CD8+浸潤細胞比例增加,沒有檢測到活性B細胞和NK細胞。Gangemi等和Drago等分別對玫瑰糠疹患者進行血清細胞因子檢測研究,結果發(fā)現(xiàn)患者血清中趨化因子、IL-22、IL-17、IFN-γ、VEGF及IP-10水平升高。然而我們既往研究發(fā)現(xiàn)玫瑰糠患者血清中IFN-γ水平降低。關于玫瑰糠疹與HLA等位基因及單倍型之間相關性研究甚少。2006年Miranda等對30例非裔巴西玫瑰糠疹患者和45例正常對照進行HLA等位基因檢測,結果發(fā)現(xiàn)HLA-DQB1*04(RR=4.00,95%CI=1.20 13.28,P=0.018)在病例組的陽性率(33.3%)明顯高于正常對照(11.1%),表明HLA-DQB1*04與巴西玫瑰糠疹的發(fā)病相關。目前尚未有關于中國人玫瑰糠疹與HLA等位基因及單倍型之間的相關性研究。研究目的該課題旨在探討HLA-Ⅱ類基因與玫瑰糠疹之間的相關性,證實玫瑰糠疹的免疫學發(fā)病機制。實驗材料與方法采用病例-對照研究,收集55例玫瑰糠疹患者和90例正常對照血樣,提取DNA,應用直接測序法(PCR-SBT)進行HLA-DRB1基因分型,應用序列特異性引物-多聚酶鏈反應法(PCR-SSP)進行HLA-DQA1及HLA-DQB1基因分型,采用卡方檢驗分析這些等位基因頻率在玫瑰糠疹和正常對照之間有無差異。結果結果發(fā)現(xiàn),HLA-DQB1*03:03在玫瑰糠疹患者中的頻率明顯高于正常對照組(47.27%vs 21.11%,P=0.001;RR=2.239;95%CI:1.376-3.645)。結論研究表明,免疫系統(tǒng)參與玫瑰糠疹的發(fā)病過程。HLA-DQB1*03:03可能是玫瑰糠疹發(fā)病的危險因素。
[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- 緯 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- 緯 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,
本文編號:1914712
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