An Ultrastructural Examination of the Epitope Expression at Each Domain of Type VII Collagen in Patients with Epidermolysis Bullosa Acquisita

Eun, Chul; Moon, Sang Ho; Lee, Chang Woo

Abstract

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an autoimmune disease characterized by circulating IgG autoantibodies which bind to the type VII collagen (C-VII). The major antigenic epitopes in C-VII, to which most EBA autoantibodies react, have been considered to be present in the N-terminal noncollagenous (NC1) domain. However, a novel EBA subgroup was recently identified with circulating antibodies, which target domain(s) other than or along with the NC1 domain of C-VII. These data suggest that there might be some heterogeneity in the autoantibody specificity to bind the domain-oriented epitopes in EBA.
OBJECTIVE
The purpose of this study was to determine whether additional or independent epitopes exist in the C- terminal noncollagenous (NC2) and/or collagenous triple-helical (CTH) domain among Korean patients with EBA.
METHODS
For this investigation, postembedding, indirect, immunogold electron microscopy was performed with the sera from 10 cases of EBA, having circulating autoantibodies against C-VII. The identification of the epitope and the relevant domain in each case were determined by ultrastructural localization of the immunogold particles.
RESULTS
From 10 sera examined, all 10 cases showed deposits of gold particles confined to the area along the lamina densa (LD), without any other pattern of deposition. There was no case which revealed any independent/distinct deposits of the gold particles in the dermis below the LD. The ultrastructural locations of each domain (NC1, on the LD; NC2, 300~360 nm below the LD; CTH, between the area of NC1 and NC2) indicated that the epitopes recognized in all 10 Korean cases of EBA were expressed at the NC1 domain of C-VII. We did not find any additional or independent epitope in other domain.
CONCLUSION
The results suggest that there may not be a wide heterogeneity in the domain-oriented topographic expression of antigenic epitopes in EBA; it is highly likely that the major epitopes present in Korean EBA cases reside within the NC1 domain of C7, similar to those observed with white population.