大疱性类天疱疮免疫发病机制的研究进展

大疱性类天疱疮作为常见的自身免疫性疱病,国内外学者一直进行其发病机制的研究.目前认为,IgG是大疱性类天疱疮患者血清中主要的致病性自身抗体类型,与BP180等自身抗原结合后可同定并激活补体,导致肥大细胞脱颗粒,激活浸润的炎症细胞并使其释放蛋白水解酶,引起真表皮连接部位的重要蛋白结构受损,最终导致表皮下水疱的发生.研究表明,体液免疫和细胞免疫均参与大疱性类天疱疮的发病过程,但大疱性类天疱疮自身抗体及可能存在的自身抗原的来源及嗜酸粒细胞在发病过程中的作用尚不完全清楚.

Abstract：

Bullous pemphigoid (BP) is a common autoimmune blistering skin disease. Studies on its immunologic pathogenesis have been always carried out at home and abroad. IgG autoantibodies, which are the predominant type of pathogenic autoantibodies, can bind to multiple BP180 epitopes, result in the fixation and activation of complement, degranulation of resident mast cells, activation of infiltrating inflammatory cells and release of proteinases followed by the loss of cell-matrix adhesion structure at the dermal-epidermal junction, and finally cause the formation of subepidermal blisters. Although studies have shown that both humoral and cellular immunity are involved, little is known about the resource of autoantibodies, probalble existent autoantigens, and the roles of eosinophils in the pathogenesis of BP.     

儿童大疱性类天疱疮

报告1例儿童大疱性类天疱疮.患儿男,18个月.2个月前躯干和双下肢皮肤出现紧张性水疱、大疱,尼氏征阴性,外用糖皮质激素治疗效果不佳.皮损组织病理检查示表皮下水疱;卣接免疫荧光示:lgG、C3沉积于基膜,间接免疫荧光示抗表皮基膜抗体阳性.诊断为儿童大疱性类天疱疮,予以口服泼尼松治疗后痊愈.     

大疱性类天疱疮动物模型研究进展

大疱性类天疱疮(BP)的免疫病理学发病机制是目前研究的热点之一,而动物模型的构建为其机制的阐明提供了研究平台.BP动物模型按照构建方式的不同可分为三类:第一类是IgG的被动转移模型,即通过注射抗鼠BP180抗体诱导与人BP类似的临床及免疫病理学改变.该模型证实炎性细胞及补体等成分在BP发病过程中的作用,但无法直接说明患者体内自身抗体的致病性作用,也未能复制嗜酸性粒细胞浸润的特点;第二类是转基因鼠模型,即在BP180抗原人源化鼠动物模型基础上证实了患者体内自身抗体的致病性作用,但嗜酸性粒细胞浸润仍很少,体内模拟T、B细胞针对的主要组织相容性复合物(MHC)依赖的致病性自身抗原仍不理想;第三类是移植皮片模型,即通过移植人或鼠皮片来模拟BP发病过程.该模型证明了BP皮损中嗜酸性粒细胞的存在,但具体的作用机制仍不清楚.该文就3类动物模型的构建及其最新进展作一综述.     

Th17细胞与大疱性类天疱疮相关性研究

大疱性类天疱疮(bullous pemphigoid, BP)是一种获得性自身免疫性皮肤病,好发于老年人.既往研究认为BP为Th2细胞占优势的自身免疫性疾病.随着研究的深入,Th17细胞已成为研究的热点.其在防御胞外细菌感染、介导慢性炎症以及自身免疫病中发挥重要作用[1].白介素(IL)-23是T细胞分泌IL-17的关键触发因素,调节T细胞亚群分泌IL-17或IL-17相关细胞因子,形成IL-23/IL-17免疫应答途径.此途径在慢性肠病、自身免疫性疾病、肿瘤、变态反应性疾病等研究中已见到,而在自身免疫性大疱性皮肤病研究中却很少见到.为研究IL-17/IL-23免疫途径在BP发病中的作用机制及与临床的相关性,我们设计了本课题.     

非大疱性类天疱疮

【摘要】 非大疱性类天疱疮与大疱性类天疱疮相关,临床表现多样,多数伴有瘙痒,缺乏大疱性类天疱疮的紧张性水疱或大疱的典型临床表现,误诊率高。组织病理缺乏特异性,需要依靠直接免疫荧光、间接免疫荧光或盐裂间接免疫荧光明确诊断。部分无疱性类天疱疮会发展为大疱性类天疱疮,预后较大疱性类天疱疮好,但由于易被延迟诊断,使得控制症状的药物用量大,药物不良反应多。     

大疱性类天疱疮抗原1和2在大疱性类天疱疮并发神经系统损害中的作用

大疱性类天疱疮可见于多种神经系统疾病患者,二者并发的机制尚不清楚.动物研究证实鼠大疱性类天疱疮抗原(BPAG)1至少存在3种亚型:皮肤亚型、神经业型和肌肉亚型.BPAG2除在皮肤有表达外,在人脑神经元也有广泛表达.有可能神经系统病变导致BPAG1和BPAG2神经亚型暴露于免疫系统,产生拮抗神经亚型的抗体,与皮肤亚型发生免疫反应及交叉反应,导致大疱性类天疱疮发生.     

大疱性类天疱疮分子免疫学发病机理研究进展

大疱性类天疱疮（ＢＰ）是好发生于老年人的自身免疫性表皮下大疱性皮肤病。其发病机理尚不明,是该病的一个研究热点。本文从分子免疫学角度,就以下几方面对近几年来的研究成果作一概述。１　ＢＰ抗原（ＢＰＡＧ） ＢＰＡＧ主要有两种ＢＰＡＧ１和ＢＰＡＧ２。ＢＰＡＧ１又称ＢＷ２３０,是一种分子量为２３０ＫＤａ,位于半桥粒致密斑的一种细胞内多肽片断,由６号染色体短臂基因编码［１］。其ａ－螺旋结构中螺旋柱的Ｃ－末端是抗体结合部位,亦是自体凝集反应及与中间细丝相互作用的区域［２］。近年来对该抗原的研究较少。ＢＰＡＧ２…     

大疱性类天疱疮抗原分子的研究进展

大疱性类天疱疮存在BPAg1和BPAg2两个抗原分子,前者分子量约220～240kD,后者分子量约160～180kD。目前用分子生物学的方法已经克隆出BPAg1和BPAg2的cDNA,发现二者的碱基序列和长度截然不同。编码BPAg1的基因位于染色体6pter-q15位点,编码BPAg2的基因位于染色体10q24.3位点。BPAg的分子生物学研究进展有利于进一步探讨BP的发病机制。     

大疱性类天疱疮抗原的研究进展

大疱性天类天疱疹的两个自身抗原存在着不同的分子生物学特性，大疱性类天疱疮抗原２２０～２４０ｋＤ是人表皮基底细胞内半桥粒斑的成分，含２６０６氨基酸，空间结构可能是双螺旋。大疱性类天疱疮抗原１８０ｋＤ为跨膜蛋白，由１５７２氨基酸组成，其中有很多胶原域，推测为一种新的胶原蛋白成分，在大疱性类天疱疮的发病机制中，大疱性类天疱疮抗原１８０ｋＤ可能具有更重要的意义。     

药物诱发大疱性类天疱疮

药物诱发大疱性类天疱疮是一种由于系统及局部用药诱发的以水疱大疱为主要表现的自身免疫性疾病.其诱导药物种类繁多,包括抗生素、利尿剂、血管紧张素转化酶抑制剂等.其发病机制尚不完全清楚,但与经典的大疱性类天疱疮不同,各种药物导致疾病发生的机制亦不完全相同.本病与经典大疱性类天疱疮在临床表现方面有一定区别,但实验室检查相似.因此,临床中应注意大疱性类天疱疮患者潜在的药物诱发因素,并及时停用诱发或可疑药物.     

嗜酸性粒细胞相关因子在大疱性类天疱疮发病机制中的研究进展

 大疱性类天疱疮(BP)是一种常见的自身免疫性大疱性疾病。一直以来研究者认为针对半粒体抗原BP180和BP230的IgG型自身抗体是BP的主要发病机制。近年来发现,嗜酸性粒细胞以及IgE型自身抗体在BP的发病机制中也起着重要作用,嗜酸性粒细胞通过脱颗粒,释放细胞因子、趋化因子,抗原提呈及调节凝血功能参与BP发病。本文综述近年来嗜酸性粒细胞相关因子在BP中作用研究进展,为靶向嗜酸性粒细胞治疗BP提供思路。     

Experimental bullous pemphigoid in guinea pigs: the role of pemphigoid antibodies, complement, and migrating cells

Dermal-epidermal separation (DES) could be produced in vivo, 6 h after the injection of sera taken from patients with bullous pemphigoid into the dorsal skin of Hartley guinea pigs. DES did not occur when antihuman IgG rabbit serum was injected prior to the injection of the sera taken from patients with bullous pemphigoid. When IgG fraction from the patient's sera was injected, DES was also observed. Histologic findings in the skin specimens in vivo with concentrated sera or IgG fraction have shown DES, some cell infiltrations of neutrophils, eosinophils, and some lymphocytes similar to the skin lesions of bullous pemphigoid patients. Various reagents, such as colchicine, cytochalasin B, EDTA, and steroid were injected prior to the IgG fraction injection. DES and the migration of polymorphonuclear (PMN) leukocytes were inhibited by the preinjection of these reagents. These observations suggest that the migration of PMN leukocytes was necessary for the formation of DES. When IgG fraction was injected into C3-inactivated guinea pigs with cobra venom factor, DES was inhibited, whereas DES was not completely inhibited when IgG fraction was injected into C4-deficient guinea pigs. These results suggested that an alternative pathway may be necessary for DES.     

The association between bullous pemphigoid and neurological disorders: a systematic review

Background

Studies suggest an association between neurological disorders and bullous pemphigoid.

Objectives

The goal of this systematic review was to characterize the occurrence of neurological disorders in patients with bullous pemphigoid.

Materials & methods

We performed a systematic review of the current English literature from 1984 to June 1^st, 2015 for documented cases of coexistent BP and neurological disorders.

Results

The literature search resulted in 53 articles meeting the inclusion criteria. Patients with bullous pemphigoid had an increased risk of stroke (OR: 4.43 [95% CI: 2.69–7.28]; p<0.001), dementia (OR: 5.48 [95% CI: 3.26–9.23]; p<0.001), Parkinson’s (OR: 3.06 [95% CI: 1.97–4.77]; p< 0.001), and epilepsy/seizures (OR: 22.88 [95% CI: 2.64–198.21]; p = 0.0045). Neurological disorders preceded bullous pemphigoid in the majority of cases with a mean time interval of 6.7 years. The one-year mortality was increased in bullous pemphigoid patients who had concomitant stroke (OR: 2.87 [95% CI: 1.67–4.96]; p<0.001).

Conclusion

Bullous pemphigoid patients have an increased association with neurological disorders which may increase mortality.

     

Childhood bullous pemphigoid: a clinicopathologic study and review of the literature

Bullous pemphigoid (BP) is an acquired bullous disorder that predominantly affects the elderly. It is rare in children but when it occurs, there is considerable clinical and histologic overlap with other acquired or congenital blistering disorders. A definitive diagnosis of childhood BP requires direct immunofluorescence and, in some cases, characterization of the target antigen. Three cases of childhood BP are presented, with their histologic and immunofluorescence findings. The first was a 5-month-old male infant who presented with erythema and bullae of the palms and soles and was found to have linear deposition of IgG and C3 along the dermoepidermal junction on direct immunofluorescence (DIF). Histopathologic examination revealed a subepidermal blister containing eosinophils. Type IV collagen was demonstrated along the floor of the blister cavity by a direct immunoperoxidase technique. The second case was an 8-month-old female infant who presented with a blistering eruption of her palms and soles that then became widespread. Direct immunofluorescence showed linear IgG and C3 at the dermoepidermal junction, with laminin deposition at the base of the blister. The third case was a 7-year-old female with bullae and erosions on the vulva and vaginal mucosa. A subepidermal blister was seen on microscopic examination whereas immunofluorescence demonstrated linear IgG and C3 deposition at the basement membrane zone (BMZ). A literature review uncovered 50 cases of childhood BP confirmed by direct or indirect immunofluorescence, or both, and often with evidence of autoantibodies against either the 180 kD or the 230 kD human bullous pemphigoid antigens (BP180 or BP230). This review was used to delineate characteristics of childhood BP, including the newly proposed subtypes: infantile BP and childhood localized vulval BP. Infantile BP presents within the first year of life and is characterized by BP-like lesions on erythematous or normal acral skin. Localized vulval BP is a self-limited, nonscarring BP-like process that involves only the vulva. Both subtypes are normally self-limited and respond well to either topical or systemic steroids, if treatment is initiated before the disease becomes widespread.