血浆疗法对大疱性类天疱疮的临床疗效及与相关细胞因子的关系

发布时间：2018-04-24 14:23

本文选题：大疱性类天疱疮 + 抗BP180抗体　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:大疱性类天疱疮(BP)是严重的自体免疫性大疱性皮肤病,好发于老年人,皮损为紧张性水疱大疱,可有破溃、糜烂,常伴有剧烈瘙痒,严重的影响患者的生存质量,甚至危及生命。尽管治疗方法不断改进,但是BP的年病死率仍然较高,文献报道为13%~38%。随着社会的老龄化,患者发病呈快速增长趋势,寻求一种能被大部分患者接受的副作用小的治疗方法迫在眉睫。血浆置换可对患者炎症介质及致病性抗体进行有效清除,同时可减少糖皮质激素用量,降低糖皮质激素的副反应,对治疗重度的大疱性类天疱疮具有很好的疗效,但血浆置换价格昂贵,增加了患者的负担,经济受限,所以我科采用间断血浆输注治疗部分大疱性类天疱疮患者,取得了一定的成效。本研究分析我科近六年来收治的大疱性类天疱疮患者的临床资料,总结其临床特征、组织病理检查等,通过对比不同治疗方法治疗前后大疱性类天疱疮患者的抗体滴度,抗体亚型及相关细胞因子水平的变化,分析相关细胞因子与疾病的发生关系,评价血浆疗法(包括血浆置换及血浆输注)对大疱性类天疱疮的治疗效果,同时对其治疗机制进行探讨,为临床治疗提供新思路。方法:分析2009年12月至2015年12月期间我院皮肤科收治的111例大疱性类天疱疮患者临床资料;采用ELISA法检测经不同治疗方法包括血浆疗法和单纯激素治疗各20名大疱性类天疱疮患者治疗前后与同期来我院体检的20名健康者血清中抗BP180抗体滴度,抗BP180抗体亚型Ig G1、Ig G4含量,及相关细胞因子IL-5、IL-6、IL-8、IL-10、IL-13、IL-18、TNF-α、IFN-γ的表达情况。所有统计学处理采用SPSS21.0软件,计量资料采用均数±标准差((x|-)±s)表示,计数资料采用(n,%)表示。结果:1临床结果:1)一般情况:111例患者中,男性为62例(55.86%),女性为49例(44.14%)。年龄范围6~94岁,均值为(68.32±16.43)岁。70岁以上的发病患者占比为63.97%。从尼氏征来看,111例患者中,阴性为98例,可疑阳性为8例,阳性为5例。111例患者中,54例患者合并心血管疾病,其中9例为冠心病,45例为高血压;22例患者合并脑血管疾病;16例患者合并糖尿病。组织病理检查:108例患者为表皮下大疱,阳性率98.20%。2)治疗效果:经治疗后,血浆疗法组有效率为92.31%,单纯激素治疗组为78.94%。3)不良反应:血浆疗法组患者未出现不良反应;单纯激素治疗组出现7例不良反应(1例肝功能异常、3例血糖升高、3例口腔真菌感染)。2实验结果:1)抗BP180抗体滴度:大疱性类天疱疮患者经过不同治疗,治疗后较治疗前抗BP180抗体滴度明显下降(P0.01)。2)抗体亚型:大疱性类天疱疮患者中存在Ig G1、Ig G4抗体亚型,治疗前各Ig G亚型阳性率差异无明显统计学差异,阳性率依次为Ig G1(85%)Ig G4(75%);治疗后各Ig G亚型阳性率有所下降,但无明显统计学差异,各亚型间无统计学差异,阳性率依次为Ig G1(75%)Ig G4(55%)。3)相关细胞因子IL-5、IL-6、IL-8、IL-10、IL-13、IL-18、TNF-α、IFN-γ水平:大疱性类天疱疮患者IL-5、IL-10、IL-13、IL-18、IFN-γ水平明显高于正常对照组(P0.05);大疱性类天疱疮患者IL-6、IL-8、TNF-α与正常对照组对比无明显差异;经过不同治疗,治疗后较治疗前IL-5、IL-10、IL-13、IL-18、IFN-γ值明显下降(P0.05);血浆疗法组各指标较单纯激素治疗组治疗后下降幅度进一步升高(P0.05)。结论:1大疱性类天疱疮患者多见于70岁以上老年人,大疱性类天疱疮患者主要合并高血压病、脑血管疾病及糖尿病。2血浆疗法治疗大疱性类天疱疮有效,副作用小。3大疱性类天疱疮患者血清中存在Ig G1、Ig G4抗体亚型,治疗前各Ig G1亚型阳性率高于Ig G4亚型,治疗后两者阳性率均下降,提示与疾病的活动度有关。4 IL-5、IL-10、IL-13、IL-18、IFN-γ参与了大疱性类天疱疮的发病,反应患者的治疗效果;血浆疗法通过减少患者体内的这些相关性细胞因子,对大疱性类天疱疮患者有着显著的疗效。
[Abstract]:Objective: bullous pemphigoid (BP) is a serious autoimmune bullous dermatosis, which is well distributed in the elderly. The skin lesions are stressful bullous bullous bullous, which can have rupture, erosion and severe pruritus, which seriously affect the quality of life and even life. Although the treatment method is constantly improved, the mortality rate of BP is still higher, literature is still high, literature It is reported that with the aging of the society, 13%~38%. has a rapid growth trend, and it is imminent to seek a small side effect that can be accepted by most patients. Plasma exchange can effectively remove the inflammatory mediators and pathogenic antibodies, reduce the dose of glucocorticoids and reduce the side reaction of glucocorticoids. It is good for the treatment of severe bullous pemphigoid, but the price of plasma exchange is expensive, the burden of the patient is increased, the economy is limited, so our department uses intermittent plasma infusion in the treatment of partial bullous pemphigoid patients and has achieved certain results. This study analyzed the bullous pemphigoid patients in our department for nearly six years. The clinical data, the clinical features, the histopathological examination, and the changes in the antibody titer, the antibody subtype and the related cytokine levels of the bullous pemphigoid patients before and after the treatment were compared, and the relationship between the related cytokines and the disease was analyzed, and the plasma therapy (including plasma exchange and plasma infusion) was evaluated. The therapeutic effect of bullous pemphigoid and its treatment mechanism were discussed in order to provide new ideas for clinical treatment. Methods: the clinical data of 111 patients with bullous pemphigoid treated in the Department of Dermatology of our hospital from December 2009 to December 2015 were analyzed, and the ELISA method was used to detect the different treatment methods including plasma therapy and simple hormone. The serum anti BP180 antibody titer, the anti BP180 antibody subtype Ig G1, the Ig G4 content, and the related cytokines IL-5, IL-6, IL-8, IL-10, IL-13, IL-18, alpha, and gamma were observed before and after the treatment of 20 bullous pemphigoid patients and 20 healthy persons who came to our hospital during the same period. Using mean number + standard deviation ((x|-) + s), the count data were expressed by (n,%). Results: 1 clinical results: 1) general situation: among 111 patients, 62 cases (55.86%) and 49 women (44.14%). The average age range was 6~94 years old, the average value was (68.32 + 16.43) years older than nil's sign, and 111 patients were negative. In 98 cases, 8 cases were suspected positive, 5 cases of.111 positive, 54 patients with cardiovascular disease, including 9 cases of coronary heart disease, 45 cases of hypertension, 22 patients with cerebrovascular disease, 16 patients with diabetes. Histopathological examination: 108 patients were the epidermis blisters, positive rate 98.20%.2) treatment effect: after treatment, plasma therapy The efficacy of the group was 92.31%, the only hormone treatment group was 78.94%.3) adverse reaction: the patients in the plasma therapy group had no adverse reactions, and the simple hormone therapy group had 7 adverse reactions (1 cases of liver dysfunction, 3 cases of blood glucose increase, 3 cases of oral fungal infection).2 test results: 1) the titer of anti BP180 antibody: the patients with bullous pemphigoid were treated in different treatments, After treatment, the anti BP180 antibody titer significantly decreased (P0.01).2) antibody subtype: there were Ig G1 and Ig G4 subtypes in pemphigoid patients with bullous pemphigoid, and there was no significant difference in the positive rate of Ig G subtypes before treatment, and the positive rate was Ig G1 (85%) Ig (75%). The positive rates were Ig G1 (75%) Ig G4 (55%).3) related cytokine IL-5, IL-6, IL-8, IL-10, IL-13, IL-18, TNF- alpha level: bullous pemphigoid level was significantly higher than that of the normal control group; There was no significant difference in the contrast group. After treatment, the value of IL-5, IL-10, IL-13, IL-18, IFN- gamma decreased significantly after treatment (P0.05), and the decrease of each index in the plasma therapy group was higher than that in the simple hormone treatment group (P0.05). Conclusion: 1 pemphigoid patients were mostly seen in older people over 70 years old and bullous type. The patients with pemphigus mainly include hypertension, cerebrovascular disease and diabetes.2 plasma therapy for bullous pemphigoid, and there are Ig G1, Ig G4 subtypes in the sera of patients with small.3 bullous pemphigoid, and the positive rate of Ig G1 subtypes before treatment is higher than that of Ig G4 subtype, and the positive rates of both patients are decreased after treatment, suggesting the survival of the disease. The dynamics of.4 IL-5, IL-10, IL-13, IL-18, and IFN- gamma are involved in the pathogenesis of bullous pemphigoid and response to the treatment effect. Plasma therapy has a significant effect on bullous pemphigoid patients by reducing these related cytokines in the patient's body.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R758.66

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