Linear IgA Bullous Dermatosis of Childhood with Autoantibodies to a 230 kDa Epidermal Antigen

Abstract: Linear IgA bullous dermatosis (LABD) is an autoimmune, subepidermal disease defined on the basis of direct immunofluorescence findings. However, more recent techniques used to study bullous dermatoses suggest that LABD may be heterogeneous. A patient with LABD of childhood (chronic benign disease of childhood, CBDC) was studied by indirect immunofluorescence on salt-split skin and by Western blot in an attempt to characterize the involved autoantigen. This young girl's periorificial (mouth, genitalia), erythematovesicular lesions were diagnosed initially as herpes simplex. Histologic examination revealed eosinophilic spongiosis, suggesting the diagnosis of an autoimmune blistering disease. Direct immunofluorescence showed an exclusive linear IgA deposit at the dermoepidermal junction. Indirect immunofluorescence revealed circulating IgA autoantibodies that reacted with the epidermal side of saltsplit skin; these reacted by Western blot with a 230 kDa epidermal antigen, as in bullous pemphigoid. This case, fulfilling the diagnostic clinical and direct immunofluorescence criteria for LABD/CBDC, seems to represent IgA bullous pemphigoid. It further underscores the nosologic heterogeneity of LABD, which probably includes, apart from bullous pemphigoid, epidermolysis bullosa acquisita and cicatricial pemphigoid.     

Pemphigoid Nodularis: A Case with 230 kDa Hemidesmosomes Antigen Associated with Bullous Pemphigoid Antigen

We report a 73-year-old woman with typical clinical, histological and immunofluorescence features of pemphigoid nodularis. Direct immunofluorescence studies of prurigo nodularis-like lesions and peribullous skin showed the linear deposition of IgG and C3 at the basement membrane zone. Circulating IgG against the basement membrane was also detected by indirect immunofluorescence. The serum from the patient was shown to contain the autoantibody against 230 kDa hemidesmosomal antigen associated with bullous pemphigoid antigen.     

A Case of Linear IgA Bullous Dermatosis with Atypical Clinical and Ultrastructural Manifestations

We report a case of linear IgA bullous dermatosis which presented with atypical clinical and ultrastructural findings. The patient initially manifested small, subepidermal blisters scattered only in the seborrheic region. On follow-up, grouped vesicles developed in a circular form similar to dermatitis herpetiformis. They subsided after treatment with diaminodiaphenyl sulphon. Immunofluorescent study showed predominant linear IgA deposits accompanied with IgG and C3 along the basement membrane zone. These deposits existed at the floor of the blister. Ultrastructurally, immunoreactants were demonstrated beneath the lamina densa while separation occurred at lamina lucida.     

成人线状IgA大疱性皮病5例临床分析

目的：了解5例成人线状IgA大疱性皮病的临床特点,以提高对该病的认识。方法：对5例成人线状IgA大疱性皮病的临床资料、组织病理、免疫荧光进行分析,并对相关文献进行复习。结果：5例患者中男3例,女2例,年龄在66—87岁之间,均表现为在红斑基础上的水疱,或外观正常的皮肤上出现的水疱,病理组织活检和免疫荧光确诊为成人线状IgA大疱性皮病。结论：成人线状IgA大疱性皮病好发年龄为〉60岁的老年人,皮疹表现类似大疱性类天疱疮、疱疹样皮炎,多数兼有两病的特点,容易误诊,直接免疫荧光检查发现沿基底膜带有均质型线状IgA沉积具有诊断价值。     

线状IgA大疱性皮病合并Graves病1例

患者女,28岁。背部反复出现水疱,伴瘙痒5个月,加重并泛发至全身4天,病程中同时出现甲状腺功能亢进。皮损组织病理和直接免疫荧光检查均提示线状IgA大疱性皮病。皮肤病和甲状腺疾病分别经糖皮质激素和同位素治疗得到缓解。     

Vancomycin-induced Linear IgA Bullous Dermatosis: A Case Report and Review of the Literature

Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disease that can either occur without any apparent cause or be induced by the administration of certain drugs, the most common of which is vancomycin. We present a case of a 45-year-old woman who was diagnosed with vancomycin-induced LABD by the presence of a characteristic linear band of IgA along the basement membrane zone on direct immunofluorescence microscopy. Our patient showed complete recovery after a 2-week period during which vancomycin administration was discontinued.     

Detection of Autoantibody against 97-kD Antigen by Immunoblot,but not by Indirect Immunofluorescence,in a Patient with Linear IgA Bullous Dermatosis

A case of linear IgA bullous dermatosis in an 85-year-old man is reported. Direct immunofluorescence (IF) of the lesional skin showed linear deposition of IgA and weak deposition of IgG at the basement membrane zone. Although no circulating autoantibody was detected by indirect IF, immunoblotting analysis using NaCl-separated normal human epidermal extracts revealed a circulating IgA antibody which bound to the 97-kD antigen.     

Linear IgA disease: the IgA and IgG response to the epidermal antigens demonstrates that intermolecular epitope spreading is associated with IgA rather than IgG antibodies, and is more common in adults

BACKGROUND: Linear IgA disease (LAD; adult and childhood) is a dapsone-responsive, acquired immunobullous disorder mediated by IgA antibodies directed at target antigens within the epithelial basement membrane. These antigens have not been completely characterized. OBJECTIVES: To identify the target antigens in LAD, and to correlate these with the antibody isotype. METHODS: We used 101 LAD sera without IgG antibodies detected by indirect immunofluorescence. The sera were analysed by immunoblotting for IgA (65 adults and 36 children) and IgG (61 adults and 34 children) autoantibodies, on salt-split, urea-extracted epidermal tissue extracts. RESULTS: Antigens were targeted in LAD by IgA antibodies (54 adults and 23 children), IgG antibodies (34 adults and 19 children), and both isotypes (30 adults and 16 children). Three major antigens were recognized by IgA antibodies: LAD285 (22 adults and three children), BP230 (30 adults and eight children) and BP180 (collagen XVII), including the 97-kDa ectodomain (52 adults and 20 children). Seven 'minor' antigens were occasionally detected (18 adults and 13 children). IgA antibodies bound multiple antigens (33 adults and nine children) more frequently than single antigens (21 adults and 14 children), but the binding to multiple antigens was more restricted in children than in adults. IgG antibodies mainly bound a single antigen (29 adults and 16 children), predominantly BP180. CONCLUSIONS: There was variation in the autoantibody response within the disease and the patient, with regard to target molecules and autoantibody class. The finding that IgG as well as IgA autoantibodies predominantly target BP180 supports a pivotal role for collagen XVII in adult and childhood LAD. The IgG response was very restricted compared with IgA autoantibodies (P < 0.01). Autoantibodies from children had a more restricted antigen repertoire than from adults (P < 0.05). Epitope spreading is common in LAD and is affected by the class of autoantibody and age of the patient.     

Two Cases of Atypical Bullous Disease Showing Linear IgG and IgA Deposition in the Basement Membrane Zone

Patients showing coexistent linear IgG and IgA deposition along the basement membrane zone on direct immunofluorescence have been described as either bullous pemphigoid, epidermolysis bullosa acquisita, linear IgA bullous dermatosis, or cicatricial pemphigoid, depending on the clinical features and laboratory findings. In the present report, we describe two cases showing atypical clinical features distinct from those of other known bullous diseases. No circulating antibodies were detected by indirect immunofluorescence of normal human skin. Indirect immunofluorescence of 1 M NaCl split skin revealed IgG and/or IgA antibodies reactive with the dermal side of the split. Immunoblotting of normal human epidermal and dermal extracts showed no apparent reactivity with known autoantigens. The results suggest that there may be a unique and distinct bullous disease with linear IgG and IgA deposition at the basement membrane zone.     

大疱性类天疱疮患者血清总IgE与血清自身抗体的关系

目的 分析大疱性类天疱疮患者血清总IgE与抗BP180IgG抗体、抗BP230IgG抗体、抗表皮基底膜IgG抗体滴度(即间接免疫荧光滴度)的关系.方法 收集沈阳市第七人民医院2014年1月-2020年1月大疱性类天疱疮病例,进行回顾性分析,根据抗BP180IgG抗体、抗BP230IgG抗体阳性情况将患者分组,比较组间血...     

A case of pemphigoid gestationis with concurrent IgG antibodies to BP180, BP230 and type VII collagen

A 22‐year‐old primigravida had a pruritic, erythematous, bullous eruption on the skin during the 26th week of gestation. After delivery the eruption flared up. The diagnosis of pemphigoid gestationis was confirmed based on histopathological and immunofluorescence findings. The result of immunoblotting showed IgG autoantibodies which reacted against BP230 in epidermal extracts and 290 kDa type VII collagen in dermal extracts. The BP180 antibodies were also detected by an enzyme‐linked immunosorbent assay BP180NC16a diagnosis kit. Pulsed corticosteroid and cyclophosphamide resulted in a favourable response at the acute stage. The patient was cured in 2 years. The analysis of the patient's autoantibodies provides strong evidence for the involvement of epitope spreading in her autoimmune disease.     

A Case of Bullous Pemphigoid with Antibodies against Intercellular 130 KD Antigen

Pemphigus and bullous pemphigoid are two typical autoimmune bullous diseases that involve circulating autoantibodies directed against the epidermal cell surface and the epidermal basement membrane zone, respectively. The coexistence of pemphigus and bullous pemphigoid is rare. We describe a case of a 79-year-old man who had tense bullae and erythematous, erosive lesions on his trunk and four extremities. Histopathology revealed subepidermal blister formation without any evidence of intraepidermal acantholytic changes. Direct immunofluorescence study demonstrated deposition of IgG on the epidermal intercellular spaces, as well as along the basement membrane zone; C₃ was detected only on the latter. Indirect immunofluorescence study using monkey esophagus as a substrate demonstrated the presence of circulating antibodies against both junctional and intercellular antigens. In order to analyze the precise nature of this patient's antibodies, indirect immunofluorescence study using cultured human keratinocytes and immunoblot analyses were performed. Pemphigus vulgaris sera showed smooth and uniform staining on intercellular spaces. The patient's serum showed a granular and uneven staining pattern. Immunoblot analysis showed that the patient's serum reacted with the typical 230 kd (bullous pemphigoid) antigen and 130 kd antigen, which is close to the pemphigus vulgaris antigen.     

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.     

Bullous pemphigoid sera react specifically with various domains of BP230, most frequently with C-terminal domain, by immunoblot analyses using bacterial recombinant proteins covering the entire molecule

By immunoblot analyses of normal human epidermal extracts, the 230 kDa bullous pemphigoid antigen (BP230) is recognized by most bullous pemphigoid sera. By polymerase chain reaction using keratinocyte cDNA library as a template, we successfully amplified 3 cDNAs of about 3 kb, which covered whole human BP230 molecule. By inserting the cDNAs into bacterial expression vector pGEX, we prepared 3 different recombinant glutathione-S-transferase-fusion proteins, which roughly presented N-terminal domain, central rod domain and C-terminal domain of BP230. By immunoblotting using these 3 recombinant proteins, we demonstrated that the majority of bullous pemphigoid sera reacted clearly with multiple recombinant proteins of BP230, most frequently with C-terminal domain. We also examined sera of pemphigus vulgaris, pemphigus foliaceus and herpetiform pemphigus that showed BP230-like protein band by immunoblotting of epidermal extracts, as well as paraneoplastic pemphigus, for reactivity with the 3 recombinant proteins. In the study, we found that only very few of these non-bullous pemphigoid sera reacted with some of the recombinant proteins. These results indicate that the BP230 is specifically reacted by bullous pemphigoid sera, and that the immunoblotting using the BP230 recombinant proteins should be a useful tool for the diagnosis of bullous pemphigoid.     

Linear IgA disease: the IgA and IgG response to dermal antigens demonstrates a chiefly IgA response to LAD285 and a dermal 180-kDa protein

BACKGROUND: Linear IgA disease (LAD) of adults and children is mediated by IgA antibodies that target proteins of the epithelial adhesion complex. Most studies have concentrated on the epidermal-associated antigens; the dermal antigens remain unresolved. OBJECTIVES: To determine the dermal antigen repertoire of IgA and IgG antibodies in LAD. METHODS: Immunoblotting was carried out on salt-split and urea-extracted dermal skin extracts with IgA antibodies (63 adult and 34 childhood sera) and with IgG antibodies (49 adult and 18 childhood sera). RESULTS: Antigens were identified by IgA (61%), IgG (27%) and by both antibody isotypes (19%). LAD285 and an antigen of 180 kDa were the major dermal antigens identified, and antigens of 230 kDa, collagen VII and a protein under 100 kDa were identified less commonly. IgA autoantibodies from adults bound single antigens more frequently than multiple antigens; from children they bound single and multiple antigens equally. The binding of multiple antigens was, however, more common in children than adults. The IgG response was weaker. The 180-kDa antigen was the main IgG dermal target, and with a single exception, IgG autoantibodies targeted single antigens. CONCLUSIONS: There was an IgA and IgG response to dermal antigens in LAD; however, the dual antibody response was limited. The antibody response to LAD285 and a 180-kDa antigen (probably BP180) suggests that intermolecular epitope spreading of the antigens associated with the extracellular matrix/dermal components of the basement membrane contributes to the immunopathology of the disease. The restricted IgG response suggests that dermal-binding IgG autoantibodies are not pathologically significant.     

Linear IgA dermatosis with IgA and IgG autoantibodies to the 180 kDa bullous pemphigoid antigen (BP180): evidence for a distinct subtype

BACKGROUND: Autoantibodies in linear immunoglobulin A (IgA) disease (LAD) are reported to be of IgA class and directed against a 97-120 kDa epidermal antigen. METHODS: We report a 39-year-old woman with clinical features of LAD and with circulating IgA and IgG autoantibodies to the 180 kDa bullous pemphigoid antigen (BP180). RESULTS: Histopathology of lesional skin revealed a subepidermal blister with mixed inflammatory cell infiltrate. Direct immunofluorescence of perilesional skin showed linear deposits of IgA along the dermal-epidermal junction. The antigen specificity of the patient's circulating antibodies was determined by Western blotting and enzyme-linked immunoabsorbent assay (ELISA) using various antigen sources, including cultured human keratinocytes, dermal protein lysates, and purified laminin-5, as well as proteins corresponding to BP180, the 230 kDa bullous pemphigoid antigen (BP230), laminin-5 subunits, and collagen IV alpha1-alpha6 chains. IgA and IgG antibodies in the patient's serum were directed against BP180, and no IgA or IgG reactivity was found against the other skin antigens. CONCLUSIONS: These data provide evidence for the presence of a subtype of LAD with dual IgA and IgG autoimmune response to BP180.     

Antigen in contact sensitivity: II. Scanning immunoelectron microscopic studies of the distribution of DNP groups on the epidermal cells of guinea pigs following skin painting with DNCB

The distribution of DNP groups on epidermal single cells and epidermal sheets prepared from the skin of guinea pigs three hours after painting with 5% DNCB-ethanol solution was examined by scanning immunoelectron microscopy using bacteriophage T4 as a visual marker. The study showed that DNP groups were distributed diffusely on the surface of epidermal cells, in particular keratinocytes, and suggests that DNCB may bind to the surface components of epidermal cells when painted on the skin.     

Localized Bullous Pemphigoid: Report of a Case with an Immunofluorescence and Electron Microscopical Studies on the Lesional Distribution of 180-KD Bullous Pemphigoid Antigen, β4 Integrin,and Type VII Collagen

A 67-year-old woman with a left-sided hemiplegia had localized bullous pemphigoid demonstrating typical clinical lesions on the left pretibial skin and the radial-side skin of the right forearm. The histology showed a subepidermal blister with extensive hyperkeratosis, hypergranulosis, and acanthosis. Direct immunofluorescence revealed distinct linear deposits of IgG and C3 at the dermo-epidermal junction in the perilesional skin and in the roof of the blisters, but few deposits in nonlesional skin. Electron microscopy revealed separation in the lamina lucida. Indirect immunofluorescence of type VII collagen showed its localization in the blister floor. The distribution of the 180-KD bullous pemphigoid antigen (BPA) and β4 integrin, hemidesmosomal transmembrane proteins, were studied in the lesional skin by indirect immunofluorescence. Both 180-KD BPA and β4 integrin were localized in the blister roof. By immunoelectron microscopy, β4 integrin was detected in small groups on the cell surface facing the blister cavity. Since the epitope of the monoclonal antibody to 180-KD BPA used here is known to be localized at a distance of 20 to 50 nm from the membrane surface and this epitope retained in the blister roof, it appears that the blister was produced in the deep lamina lucida. The lesions were cleared with topical 0.05% clobetasole propionate ointment.