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C-Terminal Processing of Collagen XVII Induces Neoepitopes for Linear IgA Dermatosis Autoantibodies

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Title: C-Terminal Processing of Collagen XVII Induces Neoepitopes for Linear IgA Dermatosis Autoantibodies
Other Titles: Neoepitopes on COL17 for LAD autoantibodies
Authors: Toyonaga, Ellen Browse this author
Nishie, Wataru Browse this author →KAKEN DB
Izumi, Kentaro Browse this author →KAKEN DB
Natsuga, Ken Browse this author →KAKEN DB
Ujiie, Hideyuki Browse this author →KAKEN DB
Iwata, Hiroaki Browse this author →KAKEN DB
Yamagami, Jun Browse this author →KAKEN DB
Hirako, Yoshiaki Browse this author
Sawamura, Daisuke Browse this author →KAKEN DB
Fujimoto, Wataru Browse this author
Shimizu, Hiroshi Browse this author →KAKEN DB
Keywords: Autoimmune blistering disease
Issue Date: Dec-2017
Publisher: Elsevier
Journal Title: Journal of investigative dermatology
Volume: 137
Issue: 12
Start Page: 2552
End Page: 2559
Publisher DOI: 10.1016/j.jid.2017.07.831
PMID: 28842325
Abstract: Transmembrane collagen XVII (COL17) is a hemidesmosomal component of basal keratinocytes that can be targeted by autoantibodies in autoimmune blistering disorders, including linear IgA dermatosis (LAD). COL17 can be physiologically cleaved within the juxtamembranous extracellular NC16A domain, and LAD autoantibodies preferentially react with the processed ectodomains, indicating that the processing induces neoepitopes. However, the details of how neoepitopes develop have not been elucidated. In this study, we show that C-terminal processing of COL17 also plays a role in inducing neoepitopes for LAD autoantibodies. First, the mAb hC17-ect15 targeting the 15th collagenous domain of COL17 was produced, which showed characteristics similar to LAD autoantibodies. The mAbs preferentially reacted with C-terminally deleted (up to 682 amino acids) recombinant COL17, suggesting that C-terminal processing shows neoepitopes on the 15th collagenous domain. The LAD autoantibodies also react with C-terminal deleted COL17. Therefore, neoepitopes for LAD autoantibodies also develop after C-terminal processing. Finally, the passive transfer of the mAb hC17-ect15 into human COL17-expressing transgenic mice failed to induce blistering disease, suggesting that neoepitope-targeting antibodies are not always pathogenic. In summary, this study shows that C-terminal processing induces dynamic structural changes and neoepitopes for LAD autoantibodies on COL17.
Rights: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 豊永 愛恋

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