抗层黏连蛋白γ1类天疱疮一例研究

【摘要】 患者男,55岁。临床表现为四肢、躯干紧张性大疱,组织学表现为表皮下水疱,真皮浅层有淋巴细胞、嗜酸性粒细胞等浸润,初步诊断为大疱性类天疱疮（BP）。在血清学分析中,发现该患者血清中自身抗体与盐裂皮肤真皮侧结合,且酶联免疫吸附法未检测到BP180、BP230、Ⅶ型胶原抗体,从而排除了大疱性类天疱疮、获得性大疱性表皮松解症的诊断。通过免疫印迹、免疫沉淀检测,发现该患者血清存在与真皮侧200 000蛋白结合的抗体,综合这些特点,诊断该患者为抗P200类天疱疮,即抗层黏连蛋白γ1类天疱疮。     

首次命名淀粉样变型类天疱疮并附一例报道

本文首次提出淀粉样变型类天疱疮的概念，并报道一例。患者中年女性，躯干、四肢苔藓样皮疹伴瘙痒17年，无水疱。组织病理示：真皮乳头大量嗜酸性无定形物质沉积，结晶紫染色：阳性；DIF：真皮乳头及基底膜IgG、IgM颗粒状沉积，C3、IgA阴性；IIF：类天疱疮循环抗体IgG 1∶320阳性。人皮肤盐裂IIF：循环抗体IgG表皮侧阳性；抗BP180抗体0 U/mL，抗BP230抗体169.2 U/mL。     

血浆置换疗法治疗天疱疮、大疱性类天疱疮疗效分析

为探讨血浆置换疗法治疗天疱疮及大疱性类天疱疮的疗效；回顾性分析曾接受血浆置换疗法的10例天疱疮、7例大疱性类天疱疮患者的临床资料。结果：10例天疱疮患者血浆置换后皮损均不同程度减轻，其中4例尼氏征数日内由阳性迅速转为阴性；5例全身症状好转；4例检测天疱疮抗体滴度者，3例下降，1例无改变；3例糖皮质激素用量减少，另1例第三次血浆置换后糖皮质激素用量比第一次减少。7例大疱性类天疱疮患者血浆置换后皮损均减轻；4例全身症状减轻；4例糖皮质激素用量减少；血浆置换疗法辅助治疗天疱疮及大疱性类天疱疮可取得较好的疗效。     

血浆疗法治疗大疱性类天疱疮的临床疗效及自身抗体水平变化

目的:通过研究大疱性类天疱疮(bullous pemphigoid, BP)患者的临床资料,提高对大疱性类天疱疮的认识,并初步评价血浆疗法治疗大疱性类天疱疮的临床疗效,并探索其治疗机制。方法:2009年12月—2015年12月我院皮肤科收治的大疱性类天疱疮患者66例,28例患者接受血浆疗法联合糖皮质激素治疗,作为血浆疗法组(PT组),38例患者单纯应用糖皮质激素治疗,作为单纯糖皮质激素治疗组(HT组),比较两组的临床疗效,每组各采集16名患者的血清,以20名健康者血清作为对照,采用酶联免疫吸附(ELISA)法检测治疗前后血清中抗BP180抗体水平的变化以及抗BP180抗体亚型IgG1、IgG4水平的变化。结果:PT组有效率为92.86%,HT组为73.68%,PT组的治疗效果更为显著。两组患者治疗后抗BP180抗体滴度明显下降(P0.01),PT组较HT组下降明显(P0.01),PT组患者治疗后抗体亚型IgG1、IgG4测得的吸光度A值明显下降(P0.05)。结论:血浆疗法治疗大疱性类天疱疮有效,其机制可能与降低抗BP180抗体及抗体亚型IgG1、IgG4的水平有关。     

类天疱疮的分型及几种新的亚型

类天疱疮是一组常见的自身免疫性大疱性皮肤病.近年来随着免疫印迹技术的发展,发现几种新的类天疱疮,如抗p200类天疱疮、抗p105类天疱疮及抗p450类天疱疮等.介绍类天疱疮的临床分型、盐裂皮肤间接免疫荧光分型和分子免疫学分型,并对新近命名的抗p200类天疱疮、抗p105类天疱疮及抗p450类天疱疮的临床特征及诊断治疗进行介绍.     

自身免疫性大疱性皮肤病患者血清中IgM抗体所识别的皮肤抗原的研究

目的:研究自身免疫性大疱性皮肤病患者血清中IgM抗体所识别的皮肤抗原成分.方法:该研究共纳入10例大疱性类天疱疮患者、15例天疱疮患者(包括7例红斑/落叶型和8例寻常型).首先通过直接免疫荧光法分析受试患者皮肤中所沉积的免疫球蛋白或补体,再通过免疫印迹方法分析患者血清中的IgM抗体所识别的皮肤抗原成分.结果:在10例大疱性类天疱疮患者的皮肤中,C3、IgG、IgM单独沉积的例数分别是4例、2例、1例,IgG和C3共同沉积的2例,IgG、C3和IgA三者共同沉积的1例;在15例天疱疮患者中,C3、IgG单独沉积的例数分别是4例和2例,IgG和C3共同沉积的6例,IgM和C3共同沉积的3例.免疫印迹研究发现9例(9/10)大疱性类天疱疮患者、11例(11/15)天疱疮患者血清中的IgM抗体可以识别皮肤中分子量约80 kD的蛋白质.结论:IgM在自身免疫性大疱性皮肤病患者的皮肤中沉积的几率很低,但大多数患者血清中的IgM抗体都能够识别分子量约80 kD的皮肤抗原.     

盐裂间接免疫荧光技术在大疱性类天疱疮鉴别诊断中的应用研究

目的:探讨盐裂皮肤间接免疫荧光(IIF)技术在大疱性类天疱疮(BP)鉴别诊断中的作用.方法:应用盐裂IIF技术检测78例常规方法诊断为BP的患者血清.结果:43例血清IgG沉积于表皮侧,7例IgG沉积于双侧,11例IgG沉积于真皮侧,另有17例双侧均未见抗体沉积.结论:盐裂IIF仅能用于BP的初步鉴别诊断.     

大疱及疱疹性皮肤病

20070886大剂量静脉注射用人免疫球蛋白辅助治疗大疱性皮肤病3例；20070887 大疱性类天疱疮皮损糖皮质激素受体α和β表达的研究；20070888 米诺环素联合烟酰胺治疗25例大疱性类天疱疮；20070889 免疫抑制剂联合糖皮质激素治疗寻常型天疱疮疗效观察；[编按]     

表现为环状红斑水疱的自身免疫性表皮下水疱病25例回顾性分析

目的总结表现为环状红斑水疱的自身免疫性表皮下水疱病的临床、组织病理、免疫血清学及治疗特点。方法回顾性分析2015—2022年就诊于中国医学科学院皮肤病医院表现为环状红斑水疱的自身免疫性表皮下水疱病患者的资料。结果共纳入患者25例, 男10例、女15例, 年龄(39.21 ± 24.65)岁, 包括线状IgA大疱性皮病9例, 大疱性类天疱疮7例, 抗P200类天疱疮5例, 获得性大疱性表皮松解症4例, 20例(80%)有不同程度瘙痒。15例(60%)出现真皮组织嗜酸性粒细胞浸润, 11例(44%)外周血嗜酸性粒细胞计数增加, 7例(28%)同时有嗜酸性粒细胞组织浸润和外周血嗜酸性粒细胞升高。盐裂皮肤-间接免疫荧光及免疫印迹实验显示, 9例同时存在抗基底膜带IgG及IgA抗体, 包括4例大疱性类天疱疮、1例线状IgA大疱性皮病、2例抗P200类天疱疮、2例获得性大疱性表皮松解症;5例同时存在多种抗基底膜带靶抗原的抗体。7例大疱性类天疱疮均予系统糖皮质激素治疗, 其中5例联合免疫抑制剂, 2例联合米诺环素;线状IgA大疱性皮病、抗P200类天疱疮、获得性大疱性表皮松解症患者对抗炎药物及氨苯砜...     

婴儿大疱性类天疱疮1例

婴儿男,6月大时出现全身红斑、水疱和大疱,皮损组织病理可见真皮内嗜酸性细胞浸润,直接及间接免疫荧光显示:IgG基底膜带线状沉积。诊断:婴儿大疱性类天疱疮。糖皮质激素治疗有效。1岁以内婴儿大疱性类天疱疮国内报道少见。     

Anti-p200 pemphigoid responding to dapsone

Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Clinical presentation is similar to standard bullous pemphigoid (BP) but mucous membranes and cephalic lesions are more frequent. Histology and direct immunofluorescence (IF) are identical to BP but indirect IF discloses linear deposits of immunoglobulin G (IgG) on the dermal side of artificial salt-split skin. Specific diagnosis is based on western immunoblotting that shows circulating IgG recognizing a 200-kDa protein localized on the dermal extract. The 200-kDa antigen was recently identified as laminin γ1. Anti-p200 pemphigoid should be considered before all atypical or topical steroid-resistant bullous disease, as well as mucous membranes pemphigoid or epidermolysis bullosa acquisita. Dapsone appears to be the most effective treatment and should be used as the first option in combination with topical steroids. In this report, we describe the case of a patient with a typical clinical and immunopathological anti-p200 pemphigoid, responding to a combination of topical steroids and dapsone.     

Two cases of subepidermal blistering disease with anti-p200 or 180-kD bullous pemphigoid antigen associated with psoriasis

We describe two patients with psoriasis vulgaris who subsequently developed a subepidermal blistering disease which disclosed IgG and C3 at the basement membrane zone in direct immunofluorescence. The first case was a 75-year-old Japanese man with herpetiform lesions. Histopathology showed neutrophil infiltration. IgG antibodies bound to the dermal side of the salt-split skin. Immunoblot analysis identified a 200-kD antigen in dermal extracts. The second case was a 70-year-old Japanese man. Histopathology showed eosinophil infiltration. IgG antibodies bound to the epidermal side of salt-split skin. Immunoblot analysis identified a 180-kD bullous pemphigoid (BP) antigen in epidermal extracts. We review the clinical and pathological features of psoriatic patients who presented a subepidermal blistering disease in which antigens were detected by immunoblot analysis; i.e., anti-p200 pemphigoid (14 cases) or BP (12 cases). There were few distinct clinical differences between two diseases. However, neutrophils were predominant in anti-p200 pemphigoid, while eosinophils were predominant in BP. After blister formation, ciclosporin was used effectively in addition to systemic steroids in the treatment of anti-p200 pemphigoid. On the other hand, ciclosporin was not used in the treatment of BP with psoriasis.     

Penicillin-induced anti-p200 pemphigoid: an unusual morphology

We report here a case of a 52-year-old woman with erythema gyratum repens-like lesions appearing during anti-p200 pemphigoid, probably induced by oral penicillin. The diagnosis of anti-p200 pemphigoid was made by the presence of in vivo bound and circulating IgG anti-basement membrane zone auto-antibody reactive with the dermal side of salt-split skin and with 200 kDa protein in dermal extract on Western immunoblot. Laser scanning confocal microscopic study disclosed the localization of IgG at the lamina lucida-lamina densa border. Skin lesions responded poorly to high dose of prednisone and the combination of prednisone and dapsone. When methotrexate was added, skin lesions healed within 3 weeks. To our knowledge, erythema gyratum repens-like lesions have not been described previously in this disorder. Thus, we have expanded the clinical morphological spectrum of patients with anti-p200 pemphigoid and first described a patient whose disorder was probably drug-induced.     

Case of subepidermal autoimmune bullous disease with psoriasis vulgaris reacting to both BP180 C‐terminal domain and laminin gamma‐1

A number of cases of psoriasis vulgaris developing bullous skin lesions have been diagnosed as either bullous pemphigoid with antibodies to the 180‐kDa bullous pemphigoid antigen (BP180) non‐collagenous 16a (NC16a) domain or anti‐laminin‐γ1 (p200) pemphigoid. We report a case of subepidermal bullous disease with psoriasis vulgaris, showing antibodies to both BP180 C‐terminal domain and laminin‐γ1. A 64‐year‐old Japanese man with psoriasis vulgaris developed exudative erythemas and tense bullae on the whole body but he did not have mucosal involvement. The blistering lesion showed subepidermal blisters histopathologically. In indirect immunofluorescence of 1 mol/L NaCl‐split skin, immunoglobulin (Ig)G antibodies reacted with both the epidermal and dermal side. Immunoblotting showed positive IgG with recombinant protein of BP180 C‐terminal domain and 200‐kDa laminin‐γ1 in normal human dermal extract.     

病情与外周血嗜酸粒细胞计数平行的大疱性类天疱疮一例

报告1例病情与外周血嗜酸粒细胞计数相平行的大疱性类天疱疮.患者男,65岁.全身泛发红斑、水疱1个月,加重15天.皮肤科检查:皮损泛发头面颈、躯干、四肢及会阴部,基本损害为正常皮肤或红斑基础上出现大小不等的水疱,疱液为草黄色,散在红色糜烂面,尼氏征阴性,部分皮损表面敷以灰褐色痂片,以胸背部、四肢尤为严重.组织病理、直接免疫荧光、间接免疫荧光及盐裂皮肤直接免疫荧光检查结果符合大疱性类天疱疮.入院后依据病情变化,先后给予3次糖皮质激素冲击治疗,治疗过程中,定期监测血常规,提示外周血嗜酸粒细胞计数随病情波动.     

A subepidermal blistering disease with histopathological features of dermatitis herpetiformis and immunofluorescence characteristcs of bullous pemphigoid: a novel subepidermal blistering disease or a variant of bullous pemphigoid?

A 64-year-old man presented with a bullous eruption which clinically and histopathologically resembled dermatitis herpetiformis. However, direct immunofluorescence analysis showed IgG deposits at the basement membrane zone, indicating a relationship with bullous pemphigoid or epidermolysis bullosa acquisita. Indirect immunofluorescence studies on salt-split skin showed binding of IgG mainly on the dermal side of the blister. Immunoblot analysis revealed a novel 200 kDa dermal antigen that could be associated with a major pathogen in this blistering a disease. The histopathological similarity to dermatitis herpetiformis and the immunofluorescence findings indicating bullous pemphigoid or epidermolysis bullosa acquisita seem typical of a distinct subepidermal blistering disease characterized by this 200 kDa antigen. However, the pathogenetic role of autoantibodies against this antigen should be further elucidated before confirming whether this case represents a novel subepidermal blistering disease or a special variant of bullous pemphigoid.     

Circulating IgA and IgE autoantibodies in antilaminin‐332 mucous membrane pemphigoid

Background Antilaminin‐332 mucous membrane pemphigoid (MMP) is a chronic autoimmune bullous disease that is often associated with internal malignancy. IgG autoantibodies against laminin‐332 in patients with MMP are well documented; however, IgA and IgE autoantibodies against laminin‐332 have not yet been described. Objectives To characterize IgA and IgE autoantibodies binding to laminin‐332 in sera from patients with antilaminin‐332 MMP. Methods Sera and skin samples from four patients who met the following criteria were used: (i) subepidermal blistering lesions present on the mucous membranes; (ii) in vivo deposition of IgG along the epidermal basement membrane zone of sampled skin; (iii) circulating IgG antibasement membrane zone antibodies that react with the dermal side of salt‐split normal human skin; and (iv) circulating IgG autoantibodies that do not show positivity against type VII collagen or 200‐kDa protein (p200 antigen) in immunoblot analysis using dermal extracts. Circulating IgG/IgA/IgE class autoantibodies against laminin‐332 were determined by immunoblotting. Results Circulating IgG autoantibodies against the γ2, α3/γ2, α3 and α3/β3/γ2 subunits of laminin‐332 were demonstrated in sera from four patients, respectively. Serum from one of the four patients showed IgA reactivity with the α3/β3/γ2 subunits of laminin‐332. Serum from one of the four patients showed IgE reactivity with the γ2 subunit of laminin‐332. The control sera failed to display IgG/IgA/IgE reactivity to laminin‐332. Conclusions In addition to IgG autoantibodies, circulating IgA and IgE autoantibodies against laminin‐332 are detectable in a subset of patients with antilaminin‐332 MMP.     

Lichen planus pemphigoides with circulating autoantibodies against 200 and 180 kDa epidermal antigens

We describe a case of lichen planus pemphigoides with circulating autoantibodies against 200 and 180 kDa epidermal antigens. A 24-year-old man presented pruritic erythematous patches with occasional central blister formation on the face, neck, and trunk and erythematous hyperkeratotic patches on the elbows and feet for 10 months. Histopathological findings of the neck and plantar lesions were consistent with lichen planus. Direct immunofluorescence studies from both lesions showed a linear deposition of IgG and C3 and cytoid bodies along the basement membrane zone. Indirect immunofluorescence studies demonstrated circulating IgG antibodies deposited on the epidermal side of salt-split skin. Immunoblot analysis using epidermal extract showed that the patient's serum reacted with 180 kDa bullous pemphigoid antigen (BPAG2) and a 200 kDa antigen. The cutaneous lesions almost cleared with a low dose of prednisolone and acitretin.     

Clinical, histopathologic, and therapeutic aspects of subepidermal autoimmune bullous diseases with IgG on the floor of salt-split skin

BACKGROUND: About 12% of patients with subepidermal autoimmune bullous disease and immunoglobulin G (IgG) at the dermal-epidermal junction present diseases other than bullous pemphigoid. MATERIALS AND METHODS: We report the clinical, histopathologic, and therapeutic aspects of eight cases of subepidermal bullous disorder with IgG on the floor of salt-split skin. RESULTS: A predominant neutrophilic infiltrate was detected in six of the eight patients. In one patient, the inflammatory infiltrate was neutrophilic and eosinophilic in the same proportion. A good response to dapsone alone or combined with prednisone was observed in six patients. CONCLUSIONS: The salt-split skin direct immunofluorescence test is useful for its diagnostic and therapeutic implications.     

Pemphigoid nodularis: a report of three cases and review of the literature

Many variants of bullous pemphigoid have been reported, some of which are clinically very atypical. One of the rarest variants is pemphigoid nodularis. We report three patients with this distinct entity. In all three cases patients initially presented with prurigo-like lesions and in one case nodular lesions preceded the onset of blistering by many months. Direct immunofluorescence was positive in all cases, with linear basement membrane zone deposition of IgG and C3. Circulating IgG antibasement membrane antibody was detected in two cases. and in these two patients on salt-split immunofluorescence the antibodies bound to the roof of the bullae.