Anti-BP180-type mucous membrane pemphigoid immunoglobulin G shows heterogeneity of internalization of BP180/collagen XVII into keratinocyte cytoplasm

Anti-BP180-type mucous membrane pemphigoid (BP180-MMP) is a rare autoimmune subepidermal blistering disease that targets the C terminus of BP180 / collagen XVII. Currently, the pathomechanism of BP180-MMP is not well understood. We reported previously that immunoglobulin G (IgG) from patients with bullous pemphigoid (BP) can induce internalization of BP180 via a macropinocytic pathway, which depletes BP180 and weakens epidermal cell–matrix integrity. The purpose of the present study was to elucidate the pathomechanism of BP180-MMP. Immunohistochemistry of biopsy specimens from two patients with BP180-MMP revealed that one patient had BP180 internalization, but the other did not. In live-cell imaging using IgG from patients with BP180-MMP on several keratinocyte cell lines, IgG from only three out of the seven patients was associated with BP180 internalization into the cytoplasm. Our results suggest that IgG from patients with BP180-MMP shows heterogeneity of internalization of BP180. This variability in BP180 internalization in patients with BP or BP180-MMP may lead to differences in clinical presentation.