Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen.

Woodley, David T.; O’Keefe, Edward J.; McDonald, J A; Reese, Melinda J.; Briggaman, Robert A.; Gammon, W. Ray

doi:10.1172/jci113024

Cited by 26 publications

(18 citation statements)

References 36 publications

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“…One possibility is that these interactions are important for the adherence of the cutaneous basement membrane to the papillary dermis. Fibronectin is known to selfaggregate, and this property, along with its affinity for type VII collagen (47), may play a role in the assembly of type VII collagen molecules into antiparallel dimers and/or cross-aggregation of these dimers into anchoring fibrils. In the context of collagen type I binding, anchoring fibrils have been proposed to be capable of entrapping other components of the dermal connective tissue, such as the broad, banded collagen fibrils consisting primarily of types I and III collagens (44,48).…”

Section: Discussionmentioning

confidence: 99%

Interactions of the Amino-terminal Noncollagenous (NC1) Domain of Type VII Collagen with Extracellular Matrix Components

Chen

Marinkovich

Veis

et al. 1997

Journal of Biological Chemistry

168

139

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Type VII collagen, the major component of anchoring fibrils, consists of a central collagenous triple-helical domain flanked by two noncollagenous domains, NC1 and NC2. The NC1 domain contains multiple submodules with homology to known adhesive molecules including fibronectin type III-like repeats and the A domain of von Willebrand factor. In this study, we produced the entire NC1 domain of human type VII collagen in the stably transfected human kidney 293 cell clones and purified large quantities of the recombinant NC1 protein from serum-free culture media. The recombinant NC1 formed interchain disulfide-bonded dimers and trimers and was N-linked glycosylated. Tunicamycin inhibited the cellular secretion of NC1, suggesting that N-linked glycosylation may play a role in NC1 secretion. The recombinant NC1 was indistinguishable from the authentic NC1 obtained from human amnions or WISH cells with respect to N-linked sugar content, electrophoretic mobility, rotary shadow imaging, and binding affinity to type IV collagen. Purified recombinant NC1, like authentic NC1, also bound specifically to fibronectin, collagen type I, and a laminin 5/6 complex. Both monomeric and trimeric forms of NC1 exhibited equal affinity for these extracellular matrix components, suggesting that the individual arms of NC1 can function independently. The multiple interactions of NC1 with other extracellular matrix components may support epidermal-dermal adhesion.Type VII collagen, a genetically distinct member of the collagen family, resides within the basement membrane zone (BMZ) 1 beneath stratified squamous epithelium (1, 2). Type VII collagen is a major component of anchoring fibrils, attachment structures within the basement membrane between the epidermis and dermis of human skin (3, 4). In inherited forms of dystrophic epidermolysis bullosa (DEB), anchoring fibrils are diminutive and/or reduced in number (5-7). Epidermolysis bullosa acquisita (EBA), an acquired autoimmune form of epidermolysis bullosa, is characterized by circulating and tissuebound IgG autoantibodies against type VII collagen (8, 9). Ultrastructural studies have demonstrated a dramatic paucity of anchoring fibrils within the dermal-epidermal junction of patients with EBA (10). These observations suggest that type VII collagen plays an important role in maintaining epidermaldermal adherence. Type VII collagen has been cloned, and a genetic linkage has been established between the inherited forms of DEB and type VII collagen (11)(12)(13)(14). Type VII collagen is composed of three identical ␣ chains, each consisting of a 145-kDa central collagenous triple-helical segment characterized by repeating Gly-X-Y amino acid sequences, flanked by a large 145-kDa amino-terminal, noncollagenous domain (NC1), and a smaller 34-kDa carboxyl-terminal noncollagenous domain (NC2) (4, 15). In the extracellular space, the individual type VII collagen molecules form antiparallel tail-to-tail dimers with a small carboxyl-terminal overlap, and a portion of the NC2 domain is proteolytically ...

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Section: Discussionmentioning

confidence: 99%

Interactions of the Amino-terminal Noncollagenous (NC1) Domain of Type VII Collagen with Extracellular Matrix Components

Chen

Marinkovich

Veis

et al. 1997

Journal of Biological Chemistry

168

139

View full text Add to dashboard Cite

show abstract

“…It is thought that these interactions may be important for the integrity of basement membranes and in maintaining epidermaldermal adherence. Recently, we have shown that the EBA antigen, like most collagens, has marked affinity for fibronectin, another major matrix component of skin that is concentrated near the BMZ (31). The skin blisters in EBA often occur in the absence of clinical or histological inflammation (1).…”

Section: Discussionmentioning

confidence: 99%

Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen.

Woodley¹,

Burgeson²,

Lunstrum³

et al. 1988

J. Clin. Invest.

Self Cite

321

143

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Epidermolysis bullosa acquisita (EBA) is a severe, chronic blistering disease of the skin. EBA patients have circulating and tissue-bound autoantibodies to a large (M, = 290,000) macromolecule that is localized within the basement membrane zone between the epidermis and dermis of skin, the site of blister formation. The "EBA antigen" is known to be distinct from laminin, heparan sulfate proteoglycan, fibronectin, the bullous pemphigoid antigen, elastin, and collagen types I, II, III, IV, and V. Sera from patients with EBA, two monoclonal antibodies to the EBA antigen, and a monoclonal antibody to the carboxyl terminus of type VII procollagen identically label human amnion and skin by immunofluorescent and immunoelectron microscopy. Western immunoblots of the EBA antigen extracted from skin and of type VII procollagen labeled with the above sera and antibodies are identical. None of the sera or antibodies labels Western blots of pepsinized type VII collagen which is missing the globular amino and carboxyl terminal domains. These data show that the EBA antigen is the carboxyl terminus of type VII procollagen.

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“…The 612-codon COL7A1 open reading frame in this patient encodes the most immunogenic part of the type VII collagen NC1 domain, namely the cartilage matrix protein subdomain. [36][37][38][39] Expression of this protein region in patient 10, and the development of immune tolerance to the major epitopes therein, may thus explain this moderate naive response to full-length type VII collagen.…”

mentioning

confidence: 99%

Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa

et al. 2010

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Recessive dystrophic epidermolysis bullosa (RDEB) is a severe genodermatosis caused by loss-of-function mutations in COL7A1 encoding type VII collagen, the component of anchoring fibrils. As exogenous type VII collagen may elicit a deleterious immune response in RDEB patients during upcoming clinical trials of gene therapies or protein replacement therapies, we developed enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot (ELISPOT) assays to analyze B-and T-cell responses, to the full-length type VII collagen. The ELISA was highly sensitive and specific when tested against sera from 41 patients with epidermolysis bullosa acquisita (EBA), and the IFN-g ELI-SPOT detected a cellular response that correlated with ongoing EBA manifestations. Both tests were next applied to assess the risk of an immune response to type VII collagen in seven RDEB patients with a range of type VII collagen expression profiles. Immune responses against type VII collagen were dependent on the expression of type VII collagen protein, and consequently on the nature and position of the respective COL7A1 mutations. These immunologic tests will be helpful for the selection of RDEB patients for future clinical trials aiming at restoring type VII collagen expression, and in monitoring their immune response to type VII collagen after treatment.

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Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen.

Cited by 26 publications

References 36 publications

Interactions of the Amino-terminal Noncollagenous (NC1) Domain of Type VII Collagen with Extracellular Matrix Components

Interactions of the Amino-terminal Noncollagenous (NC1) Domain of Type VII Collagen with Extracellular Matrix Components

Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen.

Immune reactivity to type VII collagen: implications for gene therapy of recessive dystrophic epidermolysis bullosa

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