The lupus band: do the autoantibodies target collagen VII?
BACKGROUND: Circulating autoantibodies directed against basement membrane zone (BMZ) components from patients with bullous pemphigoid and epidermolysis bullosa acquisita have been used to identify their target antigen in the skin and to confirm pathogenicity. Although the pattern of immunofluorescen...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1797059207102464000 |
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| author | Alahlafi, A Wordsworth, P Wojnarowska, F |
| author_facet | Alahlafi, A Wordsworth, P Wojnarowska, F |
| author_sort | Alahlafi, A |
| collection | OXFORD |
| description | BACKGROUND: Circulating autoantibodies directed against basement membrane zone (BMZ) components from patients with bullous pemphigoid and epidermolysis bullosa acquisita have been used to identify their target antigen in the skin and to confirm pathogenicity. Although the pattern of immunofluorescence in those diseases is similar to the lupus band, little is known about the origin and pathogenesis of the lupus band. Identifying the binding sites of the lupus band could provide a clue to the nature of the autoantigen that stimulates autoantibody formation in the skin of patients with systemic lupus erythematosus (SLE) and might provide valuable insight into the factors that influence the localization and pathogenicity of the lupus band. OBJECTIVES: To investigate the relation between the lupus band and the main BMZ components and to identify the target epitopes of autoantibodies deposited in the skin of patients with SLE. METHODS: Colocalization of the main components of the skin BMZ in nonlesional SLE skin with the lupus band was investigated using conventional immunofluorescence and confocal laser scanning microscopy. The effect of collagenase and pepsin on the expression of the lupus band was correlated with the differential sensitivity of these proteases on the collagenous and noncollagenous (NC) domains of collagen VII. Reactivity of sera from patients with SLE to a complete recombinant human NC1 domain of type VII collagen was then investigated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Near complete colocalization of the lupus band with collagen VII was found in this study, and chemical degradation of the skin attenuated the expression of the lupus band. Collectively, the NC1 domain of collagen VII was suggested as the target antigen of the lupus band, but none of the sera from patients with SLE reacted with recombinant NC1 domain-coated ELISA plates. Alternative explanations for the results of the colocalization of the lupus band with collagen VII are discussed. CONCLUSIONS: The lupus band colocalized with collagen type VII. The findings of this study ruled out the NC1 domain of collagen VII as a target antigen for circulating autoantibodies in SLE patients with no clinical evidence of blistering. Further studies are required to determine if other regions of collagen VII or another BMZ component is the target antigen for the immunoglobulins of the lupus band. |
| first_indexed | 2024-03-06T20:00:55Z |
| format | Journal article |
| id | oxford-uuid:2742f6b5-d5ad-497c-8230-d179b764706d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:00:55Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:2742f6b5-d5ad-497c-8230-d179b764706d2022-03-26T12:05:55ZThe lupus band: do the autoantibodies target collagen VII?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2742f6b5-d5ad-497c-8230-d179b764706dEnglishSymplectic Elements at Oxford2004Alahlafi, AWordsworth, PWojnarowska, FBACKGROUND: Circulating autoantibodies directed against basement membrane zone (BMZ) components from patients with bullous pemphigoid and epidermolysis bullosa acquisita have been used to identify their target antigen in the skin and to confirm pathogenicity. Although the pattern of immunofluorescence in those diseases is similar to the lupus band, little is known about the origin and pathogenesis of the lupus band. Identifying the binding sites of the lupus band could provide a clue to the nature of the autoantigen that stimulates autoantibody formation in the skin of patients with systemic lupus erythematosus (SLE) and might provide valuable insight into the factors that influence the localization and pathogenicity of the lupus band. OBJECTIVES: To investigate the relation between the lupus band and the main BMZ components and to identify the target epitopes of autoantibodies deposited in the skin of patients with SLE. METHODS: Colocalization of the main components of the skin BMZ in nonlesional SLE skin with the lupus band was investigated using conventional immunofluorescence and confocal laser scanning microscopy. The effect of collagenase and pepsin on the expression of the lupus band was correlated with the differential sensitivity of these proteases on the collagenous and noncollagenous (NC) domains of collagen VII. Reactivity of sera from patients with SLE to a complete recombinant human NC1 domain of type VII collagen was then investigated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Near complete colocalization of the lupus band with collagen VII was found in this study, and chemical degradation of the skin attenuated the expression of the lupus band. Collectively, the NC1 domain of collagen VII was suggested as the target antigen of the lupus band, but none of the sera from patients with SLE reacted with recombinant NC1 domain-coated ELISA plates. Alternative explanations for the results of the colocalization of the lupus band with collagen VII are discussed. CONCLUSIONS: The lupus band colocalized with collagen type VII. The findings of this study ruled out the NC1 domain of collagen VII as a target antigen for circulating autoantibodies in SLE patients with no clinical evidence of blistering. Further studies are required to determine if other regions of collagen VII or another BMZ component is the target antigen for the immunoglobulins of the lupus band. |
| spellingShingle | Alahlafi, A Wordsworth, P Wojnarowska, F The lupus band: do the autoantibodies target collagen VII? |
| title | The lupus band: do the autoantibodies target collagen VII? |
| title_full | The lupus band: do the autoantibodies target collagen VII? |
| title_fullStr | The lupus band: do the autoantibodies target collagen VII? |
| title_full_unstemmed | The lupus band: do the autoantibodies target collagen VII? |
| title_short | The lupus band: do the autoantibodies target collagen VII? |
| title_sort | lupus band do the autoantibodies target collagen vii |
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