Epidermolysis bullosa acquisita (EBA) is an acquired blistering skin disease characterized by the presence of IgG autoantibodies that recognize type VII (anchoring fibril) collagen. In this study, we have mapped the antigenic epitopes within the type VII collagen alpha chain by Western immunoblotting analysis with sera from 19 patients with EBA, using bacterial collagenase- or pepsin-resistant portions of type VII collagen and a panel of 12 recombinant fusion proteins corresponding to approximately 80% of the primary sequence of the alpha 1 (VII) collagen polypeptide. These studies identified four major immunodominant epitopes localized within the amino-terminal, noncollagenous (NC-1) domain. In addition to EBA, sera from three patients with bullous systemic lupus erythematosus (BSLE) were tested. The pattern of epitopes recognized by these sera were similar to those noted with EBA, suggesting that the same epitopes could serve as autoantigens in both blistering conditions. In contrast, sera from healthy controls or from patients with unrelated blistering skin diseases did not react with type VII collagen epitopes. Collectively, the results indicate that the immunodominant epitopes in EBA and BSLE lie within the noncollagenous regions of type VII collagen. The precise role of the circulating autoantibodies in the pathogenesis of these blistering diseases remains to be elucidated. Conceivably, however, such antibodies could disrupt the assembly of type VII collagen into anchoring fibrils and/or interfere with their interactions with other extracellular matrix molecules within the cutaneous basement membrane zone.
J C Lapiere, D T Woodley, M G Parente, T Iwasaki, K C Wynn, A M Christiano, J Uitto
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British Journal of Dermatology | 1998 |
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Proceedings of the National Academy of Sciences | 1998 |
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Molecular cloning and characterization of a cDNA encoding canine type VII collagen non-collagenous (NC1) domain, the target antigen of autoimmune disease epidermolysis bullosa acquisita (EBA)
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Critical Reviews in Oral Biology & Medicine | 1998 |
Physicochemical characterization and differentiation of the components of the cutaneous basement membrane zone
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British Journal of Dermatology | 1997 |
Linear IgA disease: a report of two dermal binding sera which recognize a pepsin-sensitive epitope (?NC-1 domain) of collagen type VII
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British Journal of Dermatology | 1997 |
Tight Clustering of Extracellular BP180 Epitopes Recognized by Bullous Pemphigoid Autoantibodies
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Journal of Investigative Dermatology | 1997 |
Development of an ELISA for Rapid Detection of Anti-Type VII Collagen Autoantibodies in Epidermolysis Bullosa Acquisita
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Journal of Investigative Dermatology | 1997 |
Treatment of refractory epidermolysis bullosa acquisita with extracorporeal photochemotherapy
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British Journal of Dermatology | 1997 |
AUTOIMMUNE SUBEPITHELIAL BLISTERING DISEASES WITH OCULAR INVOLVEMENT
FA Caux, GJ Giudice, LA Diaz, JA Fairley |
Immunology and Allergy Clinics of North America | 1997 |
Interactions of the Amino-terminal Noncollagenous (NC1) Domain of Type VII Collagen with Extracellular Matrix Components: A POTENTIAL ROLE IN EPIDERMAL-DERMAL ADHERENCE IN HUMAN SKIN
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Plectin and human genetic disorders of the skin and muscle. The paradigm of epidermolysis bullosa with muscular dystrophy
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Colchicine for epidermolysis bullosa acquisita
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Journal of the American Academy of Dermatology | 1996 |
Localized Linear Bullous Eruption of Systemic Lupus Erythematosus in a Child
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Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta
L Rudnicka, J Varga, AM Christiano, RV Iozzo, SA Jimenez, J Uitto |
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Type VII Collagen Specifically Binds Fibronectin via a Unique Subdomain Within the Collagenous Triple Helix
JC Lapiere, JD Chen, T Iwasaki, L Hu, J Uitto, DT Woodley |
Journal of Investigative Dermatology | 1994 |
Cicatricial pemphigoid
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