人乳头瘤病毒相关皮肤病发病机制研究

发布时间：2018-05-16 17:06

本文选题：人乳头瘤病毒 + 尖锐湿疣　；参考：《中国协和医科大学》2010年博士论文

【摘要】： 【背景】人乳头瘤病毒是一广泛存在的病毒,可以引起良性(低风险型)和恶性的(高风险型)皮肤或粘膜的皮损,但关于人乳头瘤病毒的致病机制还不清楚。人乳头瘤病毒感染可能和朗格汉斯细胞,T淋巴细胞,病毒本身等因素有关,此外,还可能与部分患者的某些基因出现甲基化和细胞因子的变化有关。疣状表皮发育不良患者出现人乳头瘤病毒易感可能与EVER1/2基因的突变有关。【目的】本论文通过研究尖锐湿疣患者DNA甲基化和疣状表皮发育不良中朗格汉斯细胞和细胞因子的变化,探讨人乳头瘤病毒相关性皮肤病的发病机制。【方法】从基因角度研究尖锐湿疣的发病和DNA甲基化之间的关系,采用甲基化特异性聚合酶链式反应,对51例尖锐湿疣患者及47例正常对照进行实验,观察对人乳头瘤病毒易感的EVER1基因甲基化的阳性率,对尖锐湿疣和EVER1基因甲基化之间的关系进行研究,以探讨尖锐湿疣的发病机制。采用免疫组化方法检测疣状表皮发育不良病人中朗格汉斯细胞和细胞因子的表达情况,以研究细胞因子在其发病中的作用。选取10例疣状表皮发育不良病人的皮损,对其表皮中朗格汉斯细胞的表面标记分子CD1a和CD83,及与免疫反应相关的IL-10,IL-23和CD86三种细胞因子进行免疫组化染色并观察其表达,同时以10例正常人的眼皮标本作对照。【结果】尖锐湿疣组中甲基化阳性率为13.73%(7／51),部分甲基化率为17.65%(9／51),非甲基化率为68.62%(35／51),总的甲基化阳性率为31.38%。正常对照组的甲基化阳性率8.51%(4／47),部分甲基化率为2.13%(1／47),非甲基化率为89.36%(42／47),总的甲基化阳性率为10.64%。两组比较有显著性差异(p0.05)。在疣状表皮发育不良的所有组织中均可见到CD1a阳性表达的朗格汉斯细胞,未见CD83阳性表达的朗格汉斯细胞,且CD1a阳性的朗格汉斯细胞的计数在EV组较正常组相比明显降低且分布不均匀。疣状表皮发育不良组中IL-10,IL-23和CD86三种细胞因子的表达为阳性,而正常组有1例IL-10阳性,其余均为阴性；病例组中三种细胞因子的评分为3-6分,而正常组除了IL-10中的1例为3分,其余均为0分；病例组中三种细胞因子的阳性率为(++)-(+++),而正常组中除了IL-10中的1例为(++),其余均为(-),疣状表皮发育不良组三种细胞因子表达阳性率明显高于正常组。【结论】本研究结果显示尖锐湿疣患者甲基化发生率为31.38%,高于正常对照组(p0.05),表明尖锐湿疣的发生可能和EVER1基因启动子区的甲基化相关。在疣状表皮发育不良组中CD1a阳性的朗格汉斯细胞的变化和CD83的不表达说明朗格汉斯细胞的功能可能受到抑制,使其不能转变为成熟状态并刺激T细胞发生免疫反应,从而造成了人乳头瘤病毒的感染。而IL-10,IL-23和CD86的阳性表达说明疣状表皮发育不良的发病还可能和角质形成细胞分泌的细胞因子有关。
[Abstract]:Human papillomavirus ( HPV ) is a widely - occurring virus that can lead to benign ( low - risk ) and malignant ( high - risk ) skin or mucosal lesions , but the pathogenesis of human papillomavirus is not clear . Human papilloma virus infection may be associated with factors such as Langehan cells , T lymphocytes , virus itself , etc . In addition , methylation and changes in cytokines may be associated with some genes in some patients . The presence of human papillomavirus in patients with verrucous epidermal dysplasia may be associated with mutations in the adenovirus 1 / 2 gene .

Objective : To study the pathogenesis of human papillomavirus - related skin disease by studying the changes of cell and cytokine in DNA methylation and verrucous epidermal dysplasia in patients with Condyloma Acuminatum .

Methodology

The relationship between the pathogenesis and DNA methylation of Condyloma Acuminatum was studied from the perspective of gene . The methylation specific polymerase chain reaction was used to study 51 patients with Condyloma Acuminatum and 47 normal controls . The positive rate of methylation of HPV 1 gene susceptible to human papilloma virus was observed .

In order to investigate the role of cytokines in the pathogenesis of verrucous epidermal dysplasia , immunohistochemical staining was used to investigate the role of cytokines in the pathogenesis of verrucous epidermal dysplasia . Ten patients with verrucous epidermal dysplasia were selected to study the expression of CD1a and CD83 , IL - 10 , IL - 23 and CD83 related to immune response and to observe the expression of cytokines .

The result is not valid .

The positive rate of methylation was 13.73 % ( 7 / 51 ) , the partial methylation rate was 17.65 % ( 9 / 51 ) , the non - methylation rate was 68.62 % ( 35 / 51 ) , the total methylation rate was 31.38 % . The methylation rate of the normal control group was 8.51 % ( 4 / 47 ) , the partial methylation rate was 2.13 % ( 1 / 47 ) , the non - methylation rate was 89.36 % ( 42 / 47 ) , the total methylation rate was 10.64 % .

The positive expression of CD1a was found in all tissues of verrucous epidermal dysplasia , and the positive expression of CD1a cells was not observed . The counts of CD1a - positive cells were significantly lower in EV group than in the normal group and the distribution was not uniform . The expression of IL - 10 , IL - 23 and CD1a in patients with verrucous epidermal dysplasia was positive , while in the normal group , there were 1 case of IL - 10 positive , while the rest were negative .
The score of three cytokines in the case group was 3 - 6 , while in the normal group , one in IL - 10 was 3 and the rest was 0 .
The positive rates of three cytokines in the case group were ( ++ ) - ( ++ ) , while in the normal group , the positive rates of three cytokines were ( + ) , ( - ) and ( - ) , and the positive rates of three cytokines in the verrucous epidermal dysplasia group were significantly higher than those in the normal group .

Conclusion

The results showed that the incidence of methylation was 31.38 % in patients with Condyloma Acuminatum , which was higher than that of the normal control group ( p < 0.05 ) .

The changes of CD1a positive cells and the non - expression of CD83 in the verrucous epidermal dysplasia group suggest that the function of the cells may be inhibited so that it can not be transformed into a mature state and stimulate T cell immune response , thus causing human papillomavirus infection . The positive expression of IL - 10 , IL - 23 and CD86 suggests that the pathogenesis of verrucous epidermal dysplasia may also be related to the cytokines secreted by keratinocytes .

【学位授予单位】：中国协和医科大学
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R752

【引证文献】