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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 28 (2003), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 144 (2001), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background IgG autoantibodies against desmoglein (Dsg) 3 play a key part in the pathogenesis of pemphigus vulgaris (PV), the most severe autoimmune bullous disorder. Objectives To determine whether immunoglobulin isotypes other than IgG are detectable in the sera of patients with PV and whether a particular immunoglobulin subtype is associated with a distinct clinical phenotype of PV. Methods Sera from 41 patients with acute-onset, chronic active, and remittent PV disease with mucosal and cutaneous lesions were assayed against a baculovirus-expressed Dsg3 protein by immunoblot analysis. Results In acute-onset PV, Dsg3-reactive IgG1 was detected in nine of 15 (60%), IgG4 in 14 of 15 (93%), IgA in nine of 15 (60%) and IgE in two of 15 (13%) sera. In chronic active PV, Dsg3-reactive IgG1 was detected in 11 of 18 (61%), IgG4 in 16 of 18 (89%), IgA in 13 of 18 (72%) and IgE in two of 18 (11%) sera. In contrast, sera from patients with remittent PV disease contained only Dsg3-reactive IgG1 in six of eight (75%) and IgG4 in four of eight (50%) cases, but not Dsg3-reactive IgA or IgE. Conclusions In extension of previous findings, our study demonstrates that, in addition to IgG autoantibodies, IgA and occasionally IgE autoantibodies reactive with Dsg3 are present in acute and chronic active PV. The detection of Dsg3-reactive autoantibodies of the IgG4, IgA and IgE subclasses in active PV provides additional evidence that PV is a T-helper 2-regulated autoimmune disorder.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cicatricial pemphigoid is a heterogeneous group of autoimmune subepidermal blistering diseases associated most commonly with autoantibodies to bullous pemphigoid (BP)180 and less frequently with those to laminin 5 or type VII collagen. In addition, a few cases have been described with autoantibodies to the β4 subunit of α6β4 integrin. We describe a patient with extensive disease of ocular, oral, pharyngeal, laryngeal and genital mucous membranes that healed with scarring of conjunctivae. IgG autoantibodies bound to the dermal–epidermal junction on direct immunofluorescence (IF) microscopy and to the epidermal side of 1 mol L−1 NaCl-split skin on indirect IF microscopy. Our patient's circulating IgG recognized a 205-kDa protein in extracts of 293T cells transfected with the β4 subunit of α6β4 integrin and in the cell extract of DJM-1 cells. Our patient's IgG and IgA autoantibodies also reacted with full-length BP180 derived from epidermal extracts and the ectodomain of BP180 (LAD-1) derived from culture supernatant of keratinocytes. In addition, a weak IgG reaction with BP230 was noted. The disease rapidly responded to dexamethasone-cyclophosphamide pulse therapy, and immunoblot reactivity to both β4 integrin and BP180 decreased according to disease activity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Cicatricial pemphigoid (CP) is an autoimmune subepidermal blistering disease where autoantibodies target various components of the dermal–epidermal junction, including the bullous pemphigoid antigen 180 (BP180). Objective We determined the exact specificity of circulating IgG and IgA autoantibodies to BP180 in a large number of CP patients. Methods Twenty-six consecutive CP sera were analysed by Western blotting using a panel of cell-derived and recombinant proteins covering the entire BP180 molecule. Results Circulating autoantibodies were detected in all CP sera. Seven sera reacting with laminin-5 were excluded from further analyses; the remaining 19 sera recognized BP180, including six sera (32%) that showed only IgA reactivity to this protein. With the combined use of the soluble BP180 ectodomain (LAD-1) and recombinant BP180 NC16A, 16 of these 19 CP sera (84%) targeted BP180. IgG reactivity was preferentially found against NC16A, whereas IgA antibodies predominantly recognized LAD-1. Thirty-two per cent of the BP180-reative sera revealed reactivity with the intracellular domain of this protein. Conclusions Our findings demonstrate that autoantibodies in CP target epitopes on both extra- and intracellular domains of BP180 and highlight the importance of testing for both IgG and IgA reactivity in these patients' sera.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 143 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report the case of a patient with a widespread bullous skin disease and linear deposits of IgG and C3 at the dermal–epidermal junction using direct immunofluorescence microscopy. Indirect immunofluorescence analysis demonstrated circulating IgG autoantibodies that stained, like autoantibodies to laminin 5 and type VII collagen, the dermal side of 1 mol L−1 NaCl-split human skin. By immunoblotting dermal extracts, the patient’s serum, like serum samples from two control patients, reacted with a 200-kDa protein. Using immunoelectron microscopy, the serum labelled a component of the lower lamina lucida, but not the lamina densa/sublamina densa region, distinguishing this from the type VII collagen localization pattern. By immunofluorescence microscopy on skin sections from patients lacking either laminin 5 (Herlitz’s epidermolysis bullosa) or type VII collagen (recessive dystrophic epidermolysis bullosa of Hallopeau–Siemens), the patient’s serum retained reactivity with these test substrates. The patient’s disease responded rapidly to the use of topical corticosteroids and lesions healed without scarring or milia formation. Our results provide strong evidence for the hypothesis that the 200 kDa autoantigen is different from laminin 5 and type VII collagen. For this new disease, we propose the designation ‘anti-p200 pemphigoid’.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 142 (2000), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A 37-year-old male patient developed a bullous eruption and erythematous plaques mainly in exposed areas following prolonged sun exposure. In addition, blisters were noted on oral and nasal mucous membranes. Histopathological examination of a lesional skin biopsy revealed a subepidermal blister. Linear deposition of IgG and C3 at the epidermal basement membrane zone was revealed by direct immunofluorescence microscopy of a perilesional skin biopsy. Indirect immunofluorescence on 1 mol/L salt-split skin showed binding of autoantibodies to the dermal side of the split. Immunoblot analysis of dermal extracts demonstrated that the patient’s serum contained IgG antibodies against type VII collagen, whereas no reaction was seen with epidermal extracts or by enzyme-linked immunosorbent assay using a recombinant form of bullous pemphigoid 180. Standardized ultraviolet (UV) radiation provocation induced blistering with both UVA (13·5 J/cm2) and UVB (0·04 J/cm2) within 24 h clinically and histologically. External and systemic UV-protective medication and nine cycles of high dosage immunoglobulins given intravenously (1·2 g/kg body weight over 2–3 days every 4 weeks) resulted in the cessation of blister formation. To the best of our knowledge, this is the first report of a case of epidermolysis bullosa acquisita with sensitivity to UV.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 30 (2005), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. We report two cases of therapy-refractory BP adjuvantly treated by tryptophan immunoadsorption. In both patients, this treatment was associated with rapid clinical improvement and reduction in the required corticosteroid dosage. In addition, levels of circulating anti-BP180 autoantibodies decreased markedly. Antibodies that were eluted from the tryptophan matrix bound to BP180 and induced dermal–epidermal separation in cryosections of human skin. Our observations suggest that immunoadsorption may be a helpful adjuvant treatment in severe BP.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 135 (1996), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Most patients with epidermolysis bullosa acquisita develop an autoimmune response to the non-collagenous (NC) 1 domain of type VII collagen. We report a 4-year-old girl of white European descent presenting with widespread blistering disease involving the face, hands, genital area and oral mucosa. Histopathology revealed subepidermal blisters, and linear deposits of IgG and C3 were seen along the dermal-epidermal junction on direct immunofluorescence (IF) microscopy of a perilesional skin biopsy. On indirect IF microscopy, circulating autoantibodies exclusively stained the dermal side of 1 mol L−1 NaCl-split skin. The patient's IgG autoantibodies labelled a 290-kDa protein on Western blotting of dermal extracts, and reacted with the NC1, NC2 and triple helical domains of type VII collagen on immunoblotting of recombinant and cell-derived fragments obtained by pepsin and collagenase digestion of the full-length protein. Oral methylprednisolone and dapsone led to clearance of lesions, which healed with mild scarring and milia formation. Treatment was discontinued after 1 year and the patient has now been in remission for more than 3 years.
    Type of Medium: Electronic Resource
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