寻常型银屑病患者睡眠结构分析以及Th17和Treg研究
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摘要
银屑病是一种临床上常见的慢性、易复发的红斑鳞屑性皮肤病。由于其外观不良,迁延不愈等特点给患者精神和经济都造成了很大的负担,严重影响到患者的生活质量和社会适应力,是一种典型的心身性皮肤病。据不完全统计我国现在约有400万患者,发病率有逐年上升的趋势,国际卫生组织已将其列为影响人类健康的重要疾病。本次研究围绕与寻常型银屑病病情进展相关的患者的特征、睡眠质量、以及近几年免疫学研究热点Th17和Treg进行探索,希望能得到与疾病进展相关的一些新的信息。
第一部分与病情进展相关的寻常型银屑病患者的特征分析
目的:从群体角度分析与病情进展相关的寻常型银屑病患者特征,进而推测银屑病病情加重的可能原因。
方法:通过对693例寻常型银屑病患者进行流行病学调查和对皮疹严重程度评估,建立logistic回归模型,分析病情相关影响因素。
结果:693例寻常型银屑病患者中男性363例(52.4%),女性330例(47.6%),多元回归分析显示:性别、职业、文化程度、体重指数、初再发是银屑病加重的的主要危险因素。其中男性相对于女性为危险因素,女性病情严重的可能性只为男性的0.723倍;脑力劳动者相对于非脑力劳动者是保护因素,脑力劳动者病情加重的可能性较非脑力劳动者低;再发相对于初发是危险因素;小学及以下文化程度相对大专及以上文化程度为危险因素,其病情严重的可能性是大专及以上文化程度的1.725倍,体重指数正常相对于肥胖为保护因素,体重正常者病情严重的可能性仅为肥胖者的0.340。一般情况分析显示:女性发病早于男性,且病情较男性为轻。男性初次发病年龄高峰是20-25岁,女性发病年龄高峰为10-20岁。28.7%的患者有家族史,有遗传史者更倾向于早发型。体重指数与皮损面积呈正相关(r=0.128,p=0.001)。男性更容易超重和肥胖。男性患者不同BMI组间皮疹严重程度无差异(r=0.071,p=0.175),女性患者不同BMI组间差异显著(r=0.167,p=0.002)。
结论:我们通过多元分析的方法了解到社会心理因素在银屑病的发生、发展中起着非常重要的作用,对于疾病正确的认知、健康积极的生活态度、良好的生活方式都会帮助银屑病患者控制病情,治疗疾病。
第二部分寻常型银屑病患者的睡眠质量研究
目的:调查寻常型银屑病患者的睡眠质量及其影响因素并检测分析银屑病患者睡眠结构存在的问题。
方法:对2007年12月至2008年8月在空军总医院皮肤科门诊就诊的126名寻常型银屑病患者进行匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)问卷和自编睡眠质量影响因素问卷调查,PSQI统计结果与国内刘贤臣等研究的112例正常成人和45例失眠患者进行对照研究,了解银屑病患者的睡眠状况。对在2007年1月至2008年12就诊的28名银屑病患者进行1-3天的床垫式睡眠检测,进行睡眠结构分析。
结果:126例寻常型银屑病患者中有75例(59.5%)存在睡眠障碍;69名患者(54.8%)认为自己的睡眠质量较差;89人(70.6%)认为睡眠质量与银屑病的病情相关。PSQI均值7.35±2.29,在评分≥2分的评测项目中,入睡时间延迟得分最高;其次为日间功能障碍,第三为睡眠障碍。银屑病患者组与正常成人组比较PSQI总分及各评测项目得分均有统计学差异;银屑病患者组与失眠症患者组PSQI比较,入睡时间和睡眠障碍两个项目无统计学差异。睡眠检测结果显示银屑病患者普遍存在REM睡眠的减少的特征,同时伴有醒觉和NREM睡眠增多、在NREM睡眠中浅睡增加、深睡减少的现象。
结论:银屑病患者确实存在较为严重的睡眠问题,睡眠的恶化影响了患者的整体状态,不利于疾病的治疗。在银屑病的治疗中应有针对性地对银屑病患者进行心理健康教育,舒缓压力,改善睡眠质量。
第三部分Th17与Treg细胞与银屑病进展的研究
背景:在以往的研究认为分泌IFN-γ的Th1类细胞在银屑病的发病中发挥了主要作用。但是近年来,越来越多的证据表明Th17细胞和Treg细胞在银屑病的致病作用中也发挥了重要作用。Th17是2005年发现的新的T细胞亚群,主要分泌IL-17A和IL-17F,RORγt是其分化中的重要转录因子,其在介导自身免疫性疾病和炎症损伤中发挥了重要的致病作用。已有研究发现在银屑病患者的皮损组织中检测到IL-17的表达,但在非皮损组织中没有发现,提示IL-17在银屑病的致病机制中发挥了重要作用。Treg细胞的功能特点是介导免疫无反应性和免疫抑制性。CD4+CD25+ Treg细胞在维持对自身和外来抗原的免疫耐受中起重要作用。
目的:了解银屑病进展过程中Th17和Treg数量动态变化、功能特点以及Th17和Treg之间相互关系。
方法:选取2008年7月至2009年1月在空军总医院门诊确诊的54例寻常型银屑病患者和18例健康人进行对照研究。所有患者按照PASI评分分为3组:第一组:PASI score≤10,共27例;第二组:10 25,共9例。采用流式细胞仪、细胞内因子染色、细胞培养等方法检测外周血中Th17和Treg数量及它们之间的相互关系。并对24例寻常型银屑病患者的皮损组织进行免疫组化染色,检测皮损部位Th17和Treg数量。
结果:银屑病患者外周血和皮损组织中的Treg细胞和Th17细胞均随着疾病进展逐渐增加。银屑病患者Treg和Th17的增加随疾病进展呈正相关,但在外周血以Th17细胞增加为主,在组织原位则以Treg细胞增加为主。银屑病患者Treg细胞能够有效地抑制T细胞增殖和IFN-γ分泌,但对于Th17细胞没有直接的抑制作用。
结论:机体存在一个完美的自我控制、稳定体系,当机体出现免疫不平衡的时候,就会启动另外一种补充性免疫反应,以此来维持稳定。Th17和Treg细胞在银屑病的进展中发挥重要作用,它们共同参与了机体维持稳定的过程。
课题的创新点:
1.首次采用无捆绑、低生理、低心理负荷的微动敏感睡眠床垫对28例银屑病患者进行睡眠检测,发现银屑病患者存在着REM睡眠减少的特征性改变,提出患者睡眠结构改变可能与患者焦虑抑郁状态有关并指出可望通过改善睡眠质量达到有效防治银屑病的见解。
2.初步阐明银屑病进展过程中Th17、Treg数量的动态变化以及它们之间相互调节的关系。
Psoriasis is a clinical common chronic recurrence skin diseases. Because of affecting the appearance and often failing to recover,it brings patients both mental and economic burden. At same time seriously damage the patients quality of life and the ability to adapt society. It is a typical psychosomatic dermatosis. In China, according to incomplete statistics it’s estimated that more than four million people are suffering from this disease, and the mobility still exhibits a increasing tendency. The World Health Organization has considered it an important impact on human health diseases. The definition of health from the simple absence of disease and weakness expand to the physical, mental and social adaptation. Medical model from a simple biomedical model developed into biological-psychological-social medical model. Our study focused on disease-related patient’s characteristics, sleep quality and correlation between Th17 and Treg during psoriasis progression. We try to discover a number of new clues associated with disease.
Part 1 Epidemiological investigation carried on psoriasis vulgaris and to analysis disease-related characteristics.
Objective: Analysis from the group perspective of the patient’s disease-related characteristics and to explore the possible reasons for illness.
Methods: Firstly epidemiological surveys were made on 693 cases of psoriasis vulgaris patients with self-designed questionair by using random sampling method. Then make rash examination and estimate the severity of the illness. At last, set up logistic regression model to analyze the impact of illness-related factors.
Results: There are 363 cases of male(52.4%)and 330 cases of female(47.6%)in this survey. By logistic regression correlation analysis there were 5 terms had signification differences. Sex, occupation, education, body mass index, initial or recurrence psoriasis are the major risk factors. Men is risk factors Compares women, women have the possibility of a serious illness only 0.723 times that of men; mental is the protection factors to non-mental, mental decrease the possibility illness exacerbations; recurrence compared with the initial is the risk factors; primary school and below the relative level of education is the risk factors contrast to university education and above, the possibility is 1.725 times; the normal body mass index is protective factors for obesity, with normal body weight the possibility in a serious condition is only 0.340 of obesity. Analysis showed: female in the early onset and light condition than men. The peak of initial onset age in male is 20-25 and in female is 10-20.The number of female is was much higher than male in onset age group 5-10 years old group, different is significan(tP<0.01). Meanwhile, 10-15 years old group, compared with men and women are different(P< 0.05). 28.7% of patients have family history, genetic history of those who have early-onset more likely. Body mass index and lesion area was positively correlated (r = 0.128, p = 0.001). Male patients were often overweight and obesity. Male patients in different BMI groups no difference in the severity of skin rash (r = 0.071, p = 0.175), between different groups of female with significant differences (r = 0.167, p = 0.002).
Conclusion: Social and psychological factors in the occurrence and development of psoriasis plays a very important role. Psoriasis is a psychosomatic diseases. Social psychological factors should be attention in psoriasis treatment.
Part 2 Survey of sleeping quality and sleep structure research on psoriasis vulgaris
Objective: This study aimed at examinging the sleep quality in patients with Vulgaris Psoriasis. Its influencing factors were also investigated. Methods: Firstly, during the period ranging from Dec. 2007 to August 2008, 126 Vulgaris Psoriasis outpatients visiting the hospital clinics were measured with the Pittsburgh Sleep Quality Index (PSQI) (Buysse et al. 1989). At the same time, a Self-designed questionnaire was utilized in order to survey the factors that affect the quality of sleep in Psoriasis vulgaris. To compare the PSQI results, a control study was carried out among above psoriasis patients, 112 cases of normal adults and 45 insomnia patients(Liu Xian-chen et al. 1996). Secondly, from Jan. 2007 to Dec. 2008, 28 Vulgaris Psoriasis Volunteers for testing sleep by Micro Movement Sensitive Matress Sleep Monitoring System, then analysis of sleep structure.
Results: There were 75 cases (59.5%) of Sleep Disorders in 126 psoriasis vulgaris. 69 patients (54.8%) considered themselves of poor quality of sleep. 89 patients (70.6%) believed that the psoriasis patients' condition due to the bad quality of sleep. The mean score of PSQI was 7.35±2.29. Among the component items with a score≥2, the top one is Sleep Latency. Daytime Dysfunction and Sleep Disturbances were the second and third items, respectively. The global score and component scale scores were significantly different between psoriasis patients and the normal adult groups. There were no significantly difference between psoriasis patients and insomnia patients in Sleep Latency and Sleep Disturbances. Sleep test results showed that the prevalence of psoriasis patients with reduced REM sleep characteristics, accompanied by an increased NREM sleep and arousal. Between NREM light sleep increased and the deep sleep reduced.
Conclusion:Poor sleep quality do exist in psoriasis vulgaris, therefore comprehensive measures should be taken to improve sleep quality of psoriasis vulgaris. Meanwhile it is necessary to promote mental health education, easing the patients pressure to improve the quality of sleep.
Part 3 An correlation between Th17 and FoxP3+ Treg accumulation during psoriasis progression
Background: Psoriasis is a chronic, relapsing, immune-mediated inflammatory skin disease, characterized by hyperplasia in the epidermis, infiltration of leukocytes, including monocytes, dendrites cells and T lymphocytes, into both the dermis and the epidermis, and dilatation and growth of blood vessels. Psoriasis was generally considered to be a Th1-associated disease with a principal role for IFN-γfor a long time. However, there are growing evidence that recently recognized two novel and unique subsets of CD4+ T cells, T-helper 17 cells and CD4+CD25+ regulatory T cells, may play important roles in the pathogenesis of psoriasis. Th17 are distinct from Th1 and Th2 cells by preferentially produce interleukin (IL)-17A and F, and require RORγt as a key transcription factor for their differentiation. IL-17 expression is detectable in biopsies from lesional psoriatic skin, but not in nonlesional skin, indicated that Th17 are involved in the pathogenesis of psoriasis. Treg, which are characterized by their constitutive expression of CD25 and FoxP3 and immunological suppression, have been considered to be another T cell subset relevant to immune-mediated diseases in humans. In psoriasis, the imbalance of Treg and effector T cells has recently described by several groups, and suggested that the numerically or functionally impaired Treg in blood and lesional tissue may be the reason which lead to reduced restraint and consequent hyperproliferation of psoriatic pathogenic T cells. Objective: To explore Th17 and Treg number and function changes during the process of disease progression of psoriasis.
Methods: Blood samples were obtained from 54 psoriasis patients and 18 age- and gender-matched healthy donors. All psoriasis patients were divided into three groups according to the Psoriasis Area and Severity Index (PASI) score: 27 patients in group 1 (PASI score≤10), 18 patients in group 2 (10 25). Using flow cytometry, cell factor staining and culture Method detection the quantity of Th17 and Treg in peripheral blood and the inter-relationship between them. Paraffin-embodied lesional skin tissues from 24 psoriasis patients were employed for immunohistochemical staining.
Results: In this study, we found that both Th17 and FoxP3+ Treg were increased in psoriasis patients both in circulating serum and lesional skin tissues and were positively correlated with disease progression. But the ratio of Th17 to Treg in lesional skin tissue obviously decreased along with disease progression,while it was significantly increased in circulating and positively correlated with PASI score. IL-17 secretion of CD4+ T cells was not regulated by Treg, even though Treg exhibited significant inhibition on CD4+ T cells proliferation and IFN-γproduction. Therefore, our data suggested that there is a feed back regulation in Th17 induced-inflammation, where increased Treg might exert a suppressive effect on the hyper-immune response. These findings represent new information about the association between Th17 and Treg, which furthers our understanding of pathogenesis of psoriasis. Conclusion:Both T-helper 17 cells (Th17) and CD4+CD25+ regulatory T cells (Treg) play important roles in the pathogenesis of psoriasis.
Research Innovation:
1. It is first time use no binding, low psychosocial, low physical Micro Movement Sensitive Matress Sleep Monitoring System to detect the sleep structure in psoriasis patients and found psoriasis patients with special REM sleep changes.
2. It is first time to explore Th17 and Treg number of dynamic changes with disease progression and their mutual relations.
第一部分与病情进展相关的寻常型银屑病患者的特征分析
目的:从群体角度分析与病情进展相关的寻常型银屑病患者特征,进而推测银屑病病情加重的可能原因。
方法:通过对693例寻常型银屑病患者进行流行病学调查和对皮疹严重程度评估,建立logistic回归模型,分析病情相关影响因素。
结果:693例寻常型银屑病患者中男性363例(52.4%),女性330例(47.6%),多元回归分析显示:性别、职业、文化程度、体重指数、初再发是银屑病加重的的主要危险因素。其中男性相对于女性为危险因素,女性病情严重的可能性只为男性的0.723倍;脑力劳动者相对于非脑力劳动者是保护因素,脑力劳动者病情加重的可能性较非脑力劳动者低;再发相对于初发是危险因素;小学及以下文化程度相对大专及以上文化程度为危险因素,其病情严重的可能性是大专及以上文化程度的1.725倍,体重指数正常相对于肥胖为保护因素,体重正常者病情严重的可能性仅为肥胖者的0.340。一般情况分析显示:女性发病早于男性,且病情较男性为轻。男性初次发病年龄高峰是20-25岁,女性发病年龄高峰为10-20岁。28.7%的患者有家族史,有遗传史者更倾向于早发型。体重指数与皮损面积呈正相关(r=0.128,p=0.001)。男性更容易超重和肥胖。男性患者不同BMI组间皮疹严重程度无差异(r=0.071,p=0.175),女性患者不同BMI组间差异显著(r=0.167,p=0.002)。
结论:我们通过多元分析的方法了解到社会心理因素在银屑病的发生、发展中起着非常重要的作用,对于疾病正确的认知、健康积极的生活态度、良好的生活方式都会帮助银屑病患者控制病情,治疗疾病。
第二部分寻常型银屑病患者的睡眠质量研究
目的:调查寻常型银屑病患者的睡眠质量及其影响因素并检测分析银屑病患者睡眠结构存在的问题。
方法:对2007年12月至2008年8月在空军总医院皮肤科门诊就诊的126名寻常型银屑病患者进行匹兹堡睡眠质量指数(Pittsburgh sleep quality index,PSQI)问卷和自编睡眠质量影响因素问卷调查,PSQI统计结果与国内刘贤臣等研究的112例正常成人和45例失眠患者进行对照研究,了解银屑病患者的睡眠状况。对在2007年1月至2008年12就诊的28名银屑病患者进行1-3天的床垫式睡眠检测,进行睡眠结构分析。
结果:126例寻常型银屑病患者中有75例(59.5%)存在睡眠障碍;69名患者(54.8%)认为自己的睡眠质量较差;89人(70.6%)认为睡眠质量与银屑病的病情相关。PSQI均值7.35±2.29,在评分≥2分的评测项目中,入睡时间延迟得分最高;其次为日间功能障碍,第三为睡眠障碍。银屑病患者组与正常成人组比较PSQI总分及各评测项目得分均有统计学差异;银屑病患者组与失眠症患者组PSQI比较,入睡时间和睡眠障碍两个项目无统计学差异。睡眠检测结果显示银屑病患者普遍存在REM睡眠的减少的特征,同时伴有醒觉和NREM睡眠增多、在NREM睡眠中浅睡增加、深睡减少的现象。
结论:银屑病患者确实存在较为严重的睡眠问题,睡眠的恶化影响了患者的整体状态,不利于疾病的治疗。在银屑病的治疗中应有针对性地对银屑病患者进行心理健康教育,舒缓压力,改善睡眠质量。
第三部分Th17与Treg细胞与银屑病进展的研究
背景:在以往的研究认为分泌IFN-γ的Th1类细胞在银屑病的发病中发挥了主要作用。但是近年来,越来越多的证据表明Th17细胞和Treg细胞在银屑病的致病作用中也发挥了重要作用。Th17是2005年发现的新的T细胞亚群,主要分泌IL-17A和IL-17F,RORγt是其分化中的重要转录因子,其在介导自身免疫性疾病和炎症损伤中发挥了重要的致病作用。已有研究发现在银屑病患者的皮损组织中检测到IL-17的表达,但在非皮损组织中没有发现,提示IL-17在银屑病的致病机制中发挥了重要作用。Treg细胞的功能特点是介导免疫无反应性和免疫抑制性。CD4+CD25+ Treg细胞在维持对自身和外来抗原的免疫耐受中起重要作用。
目的:了解银屑病进展过程中Th17和Treg数量动态变化、功能特点以及Th17和Treg之间相互关系。
方法:选取2008年7月至2009年1月在空军总医院门诊确诊的54例寻常型银屑病患者和18例健康人进行对照研究。所有患者按照PASI评分分为3组:第一组:PASI score≤10,共27例;第二组:10
结果:银屑病患者外周血和皮损组织中的Treg细胞和Th17细胞均随着疾病进展逐渐增加。银屑病患者Treg和Th17的增加随疾病进展呈正相关,但在外周血以Th17细胞增加为主,在组织原位则以Treg细胞增加为主。银屑病患者Treg细胞能够有效地抑制T细胞增殖和IFN-γ分泌,但对于Th17细胞没有直接的抑制作用。
结论:机体存在一个完美的自我控制、稳定体系,当机体出现免疫不平衡的时候,就会启动另外一种补充性免疫反应,以此来维持稳定。Th17和Treg细胞在银屑病的进展中发挥重要作用,它们共同参与了机体维持稳定的过程。
课题的创新点:
1.首次采用无捆绑、低生理、低心理负荷的微动敏感睡眠床垫对28例银屑病患者进行睡眠检测,发现银屑病患者存在着REM睡眠减少的特征性改变,提出患者睡眠结构改变可能与患者焦虑抑郁状态有关并指出可望通过改善睡眠质量达到有效防治银屑病的见解。
2.初步阐明银屑病进展过程中Th17、Treg数量的动态变化以及它们之间相互调节的关系。
Psoriasis is a clinical common chronic recurrence skin diseases. Because of affecting the appearance and often failing to recover,it brings patients both mental and economic burden. At same time seriously damage the patients quality of life and the ability to adapt society. It is a typical psychosomatic dermatosis. In China, according to incomplete statistics it’s estimated that more than four million people are suffering from this disease, and the mobility still exhibits a increasing tendency. The World Health Organization has considered it an important impact on human health diseases. The definition of health from the simple absence of disease and weakness expand to the physical, mental and social adaptation. Medical model from a simple biomedical model developed into biological-psychological-social medical model. Our study focused on disease-related patient’s characteristics, sleep quality and correlation between Th17 and Treg during psoriasis progression. We try to discover a number of new clues associated with disease.
Part 1 Epidemiological investigation carried on psoriasis vulgaris and to analysis disease-related characteristics.
Objective: Analysis from the group perspective of the patient’s disease-related characteristics and to explore the possible reasons for illness.
Methods: Firstly epidemiological surveys were made on 693 cases of psoriasis vulgaris patients with self-designed questionair by using random sampling method. Then make rash examination and estimate the severity of the illness. At last, set up logistic regression model to analyze the impact of illness-related factors.
Results: There are 363 cases of male(52.4%)and 330 cases of female(47.6%)in this survey. By logistic regression correlation analysis there were 5 terms had signification differences. Sex, occupation, education, body mass index, initial or recurrence psoriasis are the major risk factors. Men is risk factors Compares women, women have the possibility of a serious illness only 0.723 times that of men; mental is the protection factors to non-mental, mental decrease the possibility illness exacerbations; recurrence compared with the initial is the risk factors; primary school and below the relative level of education is the risk factors contrast to university education and above, the possibility is 1.725 times; the normal body mass index is protective factors for obesity, with normal body weight the possibility in a serious condition is only 0.340 of obesity. Analysis showed: female in the early onset and light condition than men. The peak of initial onset age in male is 20-25 and in female is 10-20.The number of female is was much higher than male in onset age group 5-10 years old group, different is significan(tP<0.01). Meanwhile, 10-15 years old group, compared with men and women are different(P< 0.05). 28.7% of patients have family history, genetic history of those who have early-onset more likely. Body mass index and lesion area was positively correlated (r = 0.128, p = 0.001). Male patients were often overweight and obesity. Male patients in different BMI groups no difference in the severity of skin rash (r = 0.071, p = 0.175), between different groups of female with significant differences (r = 0.167, p = 0.002).
Conclusion: Social and psychological factors in the occurrence and development of psoriasis plays a very important role. Psoriasis is a psychosomatic diseases. Social psychological factors should be attention in psoriasis treatment.
Part 2 Survey of sleeping quality and sleep structure research on psoriasis vulgaris
Objective: This study aimed at examinging the sleep quality in patients with Vulgaris Psoriasis. Its influencing factors were also investigated. Methods: Firstly, during the period ranging from Dec. 2007 to August 2008, 126 Vulgaris Psoriasis outpatients visiting the hospital clinics were measured with the Pittsburgh Sleep Quality Index (PSQI) (Buysse et al. 1989). At the same time, a Self-designed questionnaire was utilized in order to survey the factors that affect the quality of sleep in Psoriasis vulgaris. To compare the PSQI results, a control study was carried out among above psoriasis patients, 112 cases of normal adults and 45 insomnia patients(Liu Xian-chen et al. 1996). Secondly, from Jan. 2007 to Dec. 2008, 28 Vulgaris Psoriasis Volunteers for testing sleep by Micro Movement Sensitive Matress Sleep Monitoring System, then analysis of sleep structure.
Results: There were 75 cases (59.5%) of Sleep Disorders in 126 psoriasis vulgaris. 69 patients (54.8%) considered themselves of poor quality of sleep. 89 patients (70.6%) believed that the psoriasis patients' condition due to the bad quality of sleep. The mean score of PSQI was 7.35±2.29. Among the component items with a score≥2, the top one is Sleep Latency. Daytime Dysfunction and Sleep Disturbances were the second and third items, respectively. The global score and component scale scores were significantly different between psoriasis patients and the normal adult groups. There were no significantly difference between psoriasis patients and insomnia patients in Sleep Latency and Sleep Disturbances. Sleep test results showed that the prevalence of psoriasis patients with reduced REM sleep characteristics, accompanied by an increased NREM sleep and arousal. Between NREM light sleep increased and the deep sleep reduced.
Conclusion:Poor sleep quality do exist in psoriasis vulgaris, therefore comprehensive measures should be taken to improve sleep quality of psoriasis vulgaris. Meanwhile it is necessary to promote mental health education, easing the patients pressure to improve the quality of sleep.
Part 3 An correlation between Th17 and FoxP3+ Treg accumulation during psoriasis progression
Background: Psoriasis is a chronic, relapsing, immune-mediated inflammatory skin disease, characterized by hyperplasia in the epidermis, infiltration of leukocytes, including monocytes, dendrites cells and T lymphocytes, into both the dermis and the epidermis, and dilatation and growth of blood vessels. Psoriasis was generally considered to be a Th1-associated disease with a principal role for IFN-γfor a long time. However, there are growing evidence that recently recognized two novel and unique subsets of CD4+ T cells, T-helper 17 cells and CD4+CD25+ regulatory T cells, may play important roles in the pathogenesis of psoriasis. Th17 are distinct from Th1 and Th2 cells by preferentially produce interleukin (IL)-17A and F, and require RORγt as a key transcription factor for their differentiation. IL-17 expression is detectable in biopsies from lesional psoriatic skin, but not in nonlesional skin, indicated that Th17 are involved in the pathogenesis of psoriasis. Treg, which are characterized by their constitutive expression of CD25 and FoxP3 and immunological suppression, have been considered to be another T cell subset relevant to immune-mediated diseases in humans. In psoriasis, the imbalance of Treg and effector T cells has recently described by several groups, and suggested that the numerically or functionally impaired Treg in blood and lesional tissue may be the reason which lead to reduced restraint and consequent hyperproliferation of psoriatic pathogenic T cells. Objective: To explore Th17 and Treg number and function changes during the process of disease progression of psoriasis.
Methods: Blood samples were obtained from 54 psoriasis patients and 18 age- and gender-matched healthy donors. All psoriasis patients were divided into three groups according to the Psoriasis Area and Severity Index (PASI) score: 27 patients in group 1 (PASI score≤10), 18 patients in group 2 (10
Results: In this study, we found that both Th17 and FoxP3+ Treg were increased in psoriasis patients both in circulating serum and lesional skin tissues and were positively correlated with disease progression. But the ratio of Th17 to Treg in lesional skin tissue obviously decreased along with disease progression,while it was significantly increased in circulating and positively correlated with PASI score. IL-17 secretion of CD4+ T cells was not regulated by Treg, even though Treg exhibited significant inhibition on CD4+ T cells proliferation and IFN-γproduction. Therefore, our data suggested that there is a feed back regulation in Th17 induced-inflammation, where increased Treg might exert a suppressive effect on the hyper-immune response. These findings represent new information about the association between Th17 and Treg, which furthers our understanding of pathogenesis of psoriasis. Conclusion:Both T-helper 17 cells (Th17) and CD4+CD25+ regulatory T cells (Treg) play important roles in the pathogenesis of psoriasis.
Research Innovation:
1. It is first time use no binding, low psychosocial, low physical Micro Movement Sensitive Matress Sleep Monitoring System to detect the sleep structure in psoriasis patients and found psoriasis patients with special REM sleep changes.
2. It is first time to explore Th17 and Treg number of dynamic changes with disease progression and their mutual relations.
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