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Anti-idiotypic Antibodies against BP-IgG Prevent Type XVII Collagen Depletion

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Title: Anti-idiotypic Antibodies against BP-IgG Prevent Type XVII Collagen Depletion
Authors: Kamaguchi, Mayumi Browse this author
Iwata, Hiroaki Browse this author →KAKEN DB
Mori, Yuiko Browse this author
Toyonaga, Ellen Browse this author
Ujiie, Hideyuki Browse this author →KAKEN DB
Kitagawa, Yoshimasa Browse this author →KAKEN DB
Shimizu, Hiroshi Browse this author →KAKEN DB
Keywords: bullous pemphigoid
type XVII collagen
intravenous immunoglobulin
idiotypic antibody
Issue Date: 27-Nov-2017
Publisher: Frontiers Media
Journal Title: Frontiers in immunology
Volume: 8
Start Page: 1669
Publisher DOI: 10.3389/fimmu.2017.01669
Abstract: Bullous pemphigoid (BP) mainly targets type XVII collagen (COL17). Intravenous immunoglobulin (IVIg) is used to treat numerous autoimmune diseases, including BP. The major mechanism of action for IVIG is thought to be its immunomodulatory effect. However, little is known about the precise mechanisms of IVIg in BP. We investigate the cellular effects of IVIg, toward treatments for BP. Keratinocytes were treated with IgG from BP patients (BP-IgG) and with IVIg, and then the COL17 expression was detected by Western blotting. Cell adhesion and ex vivo dermal-epidermal separation were also investigated for the condition with BP-IgG and IVIg. BP-IgG targeting the non-collagenous 16A domain induces the depletion of COL17 in cultured keratinocytes (DJM-1 cells). The COL17 levels in DJM-1 cells were decreased by 50% after 4 h of BP-IgG stimulation as determined by Western blotting. By contrast, BP-IgG with IVIg was found to result in 70-90% increases in COL17 and to restore adhesion to the plate. Interestingly, IVIg significantly inhibited the binding of BP-IgG to the COL17-enzymelinked immunosorbent assay plate, and this was due to anti-idiotypic antibodies against BP-IgG. When anti-idiotypic antibodies against BP-IgG in 0.02% of IVIg were depleted from IVIg, those antibodies did not exhibit inhibitory effects on COL17 depletion. When cryosections of human skin were incubated with BP-IgG in the presence of leukocytes, dermal-epidermal separation was observed. BP-IgG treatment with IVIg or anti-idiotypic antibodies did not induce such separation. These findings strongly suggest the presence of anti-idiotypic antibodies against anti-COL17 IgG in IVIg. This mechanism of IVIg could be a target for therapies against BP.
Rights: © 2017 Kamaguchi, Iwata, Mori, Toyonaga, Ujiie, Kitagawa and Shimizu.
Type: article
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 岩田 浩明

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