IgG from patients with bullous pemphigoid depletes cultured keratinocytes of the 180-kDa bullous pemphigoid antigen (type XVII collagen) and weakens cell attachment.
We have shown that binding of bullous pemphigoid (BP)-patient IgG (BP-IgG) causes the internalization of BP180 from the cell membrane. This study examined whether BP-IgG treatment can deplete cultured keratinocytes of BP180, how it affects cellular levels of alpha6 and beta4 integrins (by western blot analysis using monoclonal antibodies to these antigens), and whether it reduces adhesion of cells to the culture dish (by a vibration detachment assay). All BP-IgG or BP sera with high values of BP180-ELISA from 18 BP patients before and after oral corticosteroid treatment showed dramatically decreased BP180 in cells after 6 hours of BP-IgG stimulation, whereas alpha6 and beta4 integrin levels were not decreased. Even IgG from patients in whom oral corticosteroid had suppressed active blistering could deplete cells of BP180, as long as sera retained a high value of BP180-ELISA. On the other hand, reduction of cell BP180 content increased detachment of cells from the dish. These results suggest that BP-IgG reduces hemidesmosomal BP180 content, weakening the adhesion of hemidesmosomes to the lamina densa. In the presence of BP180 deficiency, inflammation generated by BP180 immune-complex formation might then tear the weakened lamina lucida, and this could lead to generation of the BP-specific split at the lamina lucida.
Iwata
Hiroaki
H
Department of Dermatology, Gifu Graduate School of Medicine, Gifu, Japan.
Kamio
Naoko
N
Aoyama
Yumi
Y
Yamamoto
Yukari
Y
Hirako
Yoshiaki
Y
Owaribe
Katsushi
K
Kitajima
Yasuo
Y
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001323:Autoantibodies / Q000502:physiology*; D001324:Autoantigens / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D039503:Integrin alpha6 / Q000032:analysis; D039663:Integrin beta4 / Q000032:analysis; D015603:Keratinocytes / Q000378:metabolism*; D024041:Non-Fibrillar Collagens / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D010391:Pemphigoid, Bullous / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D000097805:Collagen Type XVII
D000305:Adrenal Cortex Hormones; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D039503:Integrin alpha6; D039663:Integrin beta4; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII