Some epidermolysis bullosa acquisita sera react with epitopes within the triple-helical collagenous domain as indicated by immunoelectron microscopy

Ishii, Norito; Yoshida, Minoru; Ishida‐Yamamoto, Akemi; Fritsch, Anja; Elfert, Susanne; Bruckner‐Tuderman, Leena; Hashimoto, Takashi

doi:10.1111/j.1365-2133.2008.08952.x

Cited by 28 publications

(24 citation statements)

References 10 publications

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“…However, in our cohort of 69 EBA patients, we found no correlation of clinical phenotype with the fine specificity of anti-COL7 IgG. We do not think that reactivity to the collagenous domain of COL7 can explain these findings, as only very few patients had been described to have reactivity to epitopes located within the collagenous domain and/or the hinge region of COL7 (Ishii et al, 2009). Hence, other factors are likely to cause the different clinical phenotypes.…”

Section: Discussioncontrasting

confidence: 75%

Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters

Vorobyev

Ujiie

Recke

et al. 2015

Journal of Investigative Dermatology

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Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease of the skin and mucous membranes, characterized by autoantibodies against type VII collagen (COL7), a major component of anchoring fibrils. Different clinical EBA phenotypes are described, including mechanobullous and inflammatory variants. Most EBA patients' sera react with epitopes located within the non-collagenous 1 (NC1) domain of human COL7. However, it has remained unclear whether antibody binding to these different epitopes is pathogenically relevant. To address this issue, we generated recombinant proteins covering the entire NC1 domain. IgG reactivity with these proteins was analyzed in sera of 69 EBA patients. Most recognized clusters of epitopes throughout the NC1 domain. No correlation was detected between antibody specificity and clinical phenotype. To study the pathogenicity of antibodies specific to different NC1 subdomains, rabbit antibodies were generated. All these antibodies caused dermal-epidermal separation ex vivo. Antibodies against two of these subdomains were injected into mice carrying null mutations of mouse COL7 and the human COL7 transgene and induced subepidermal blisters. We here document that autoantibodies to COL7, independent of the targeted epitopes, induce blisters both ex vivo and in vivo. In addition, using COL7-humanized mice, we provide in vivo evidence of pathogenicity of autoantibodies binding to human COL7.

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Section: Discussioncontrasting

confidence: 75%

Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters

Vorobyev

Ujiie

Recke

et al. 2015

Journal of Investigative Dermatology

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“…It has been reported that autoantibodies in some EBA patients bind only to the central collagenous domain of type VII collagen [14]. The serum of this case may bind to the central collagenous domain of type VII collagen.…”

Section: Discussionmentioning

confidence: 96%

“…NC2 domain of type VII collagen contains minor antigenic epitopes [11,12]. Moreover, some EBA cases bind to the central collagenous domain of type VII collagen [13][14][15].…”

mentioning

confidence: 99%

Development of NC1 and NC2 domains of Type VII collagen ELISA for the diagnosis and analysis of the time course of epidermolysis bullosa acquisita patients

Saleh

Ishii

Kim

et al. 2011

Journal of Dermatological Science

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“…Detailed epitope mapping studies with sera from EBA patients [55–57] demonstrated that most autoantibodies bind to epitopes located within the noncollagenous (NC) 1 domain of COL7 (Figure 2). In only very few patients, antibody reactivity to either the collagenous domain [58] or the NC2 domain [59] can be detected.…”

Section: Identification Of Type VII Collagen As the Autoantigen Inmentioning

confidence: 99%

Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

Ludwig

2013

ISRN Dermatology

124

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Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin blistering disease. The pathogenic relevance of autoantibodies targeting type VII collagen (COL7) has been well-documented. Therefore, EBA is a prototypical autoimmune disease with a well-characterized pathogenic relevance of autoantibody binding to the target antigen. EBA is a rare disease with an incidence of 0.2 new cases per million and per year. The current treatment of EBA relies on general immunosuppressive therapy, which does not lead to remission in all cases. Therefore, there is a high, so far unmet medical need for the development of novel therapeutic options. During the last 10 years, several novel in vitro and in vivo models of EBA have been established. These models demonstrated a critical role of the genetic background, T cells, and cytokines for mediating the loss of tolerance towards COL7. Neutrophils, complement activation, Fc gamma receptor engagement, cytokines, several molecules involved in cell signaling, release of reactive oxygen species, and matrix metalloproteinases are crucial for autoantibody-induced tissue injury in EBA. Based on this growing understanding of the diseases' pathogenesis, several potential novel therapeutic targets have emerged. In this review, the clinical presentation, pathogenesis, diagnosis, and current treatment options for EBA are discussed in detail.

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Some epidermolysis bullosa acquisita sera react with epitopes within the triple-helical collagenous domain as indicated by immunoelectron microscopy

Abstract: Our results suggest that epitopes within the T-H collagenous domain of type VII collagen are recognized by IgG antibodies from some EBA sera. These antibodies appear to be found in patients with inflammatory-type EBA.

Cited by 28 publications

References 10 publications

Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters

Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters

Development of NC1 and NC2 domains of Type VII collagen ELISA for the diagnosis and analysis of the time course of epidermolysis bullosa acquisita patients

Clinical Presentation, Pathogenesis, Diagnosis, and Treatment of Epidermolysis Bullosa Acquisita

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