AI Article Synopsis
- Anti-p200 pemphigoid is linked to autoantibodies targeting an unidentified 200-kDa protein at the dermal-epidermal junction, which this study identifies as laminin gamma1.
- The study used 2D gel electrophoresis, immunoblotting, and mass spectrometry to confirm that sera from patients reacted strongly with laminin gamma1, while healthy controls showed no such reaction.
- The findings indicate that the autoantibodies in anti-p200 pemphigoid specifically recognize a modified form of dermal laminin gamma1, with crucial recognition sites located in the C-terminal region.
Article Abstract
Anti-p200 pemphigoid has been characterized by autoantibodies to an unidentified 200-kDa protein (p200) of the dermal-epidermal junction. The objective of this study was to identify p200. We performed 2D gel electrophoresis of dermal extracts and immunoblotting with patients' sera, followed by MS analysis of a unique protein band. The protein band corresponded to laminin gamma1. Anti-laminin gamma1 mAb reacted with the anti-p200 immunoprecipitates by immunoblotting. Sera from 32 patients with anti-p200 pemphigoid showed 90% reactivity to the recombinant products of laminin gamma1. None of the healthy control sera reacted with laminin gamma1. By immunoblotting, reactivity of a patient's serum with p200 was competitively inhibited by adding anti-laminin gamma1 C-terminus mAb. Purified anti-p200 IgG also inhibited the reactivity of this mAb to dermal laminin gamma1. Most laminin gamma1-positive sera showed reactivity with recombinant laminin gamma1 C-terminal E8 fragment. Reactivity of patients' sera and purified IgG to dermal laminin gamma1 was higher than reactivity to blood vessel laminin gamma1 under reducing conditions. These results suggest that laminin gamma1 is the autoantigen for patients with anti-p200 pemphigoid. The autoantibodies may specifically recognize dermal laminin gamma1 with unique posttranslational modifications. The epitope is localized to the 246 C-terminal amino acids within the coiled-coil domain. The 9 C-terminal residues are known to be critically involved in laminin recognition by integrins.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2650346 | PMC |
| http://dx.doi.org/10.1073/pnas.0809230106 | DOI Listing |
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