The Intracellular and Extracellular Domains of BP180 Antigen Comprise Novel Epitopes Targeted by Pemphigoid Gestationis Autoantibodies

Abstract

Pemphigoid gestationis (PG) is an autoimmune sub-epidermal bullous dermatosis of pregnancy associated with circulating autoantibodies targeting the extracellular non-collagenous (NC) 16A domain of bullous pemphigoid (BP) 180 antigen. In order to determine whether BP180 regions other than NC16A are recognized by PG autoantibodies, we have analyzed the reactivity of 15 PG patient sera against several BP180 antigenic sites by sensitive methods such as immunological screening and ELISA. Most PG sera tested (13 of 15) reacted with an epitope (amino acid 508-541) mapped in the NC16A domain. Of note, nine of 15 PG patient sera reacted with at least one additional antigenic site other than NC16A. Specifically, two epitopes in the BP180 extracellular domain and five epitopes in the intracellular one were recognized by three and seven PG sera, respectively. In addition, a representative intracellular epitope was recognized by PG autoantibodies as a portion of BP180 antigen both in denaturating and native conditions. Finally, reactivity against epitopes additional to NC16A was also detected at an early stage of the disease. The identification and characterization of hitherto unrecognized epitopes targeted by PG patient autoantibodies provide novel insights into the pathophysiology of humoral immune response to BP180 in PG.

A study on dermatoses of pregnancy

“…Performed on perilesional skin, DIF shows a linear band of C3 and/ or IgG at the basement membrane. Salt-split skin studies demonstrate antibody binding to the roof of the vesicle [22].…”

Pemphigoïde gravidique

“…Sa positivité permet de distinguer de manière fiable la PG des autres dermatoses prurigineuses de la grossesse [11,12].…”

Enzyme-linked immunosorbent assay and immunobullous disease

“…Specifically, two epitopes in the BP 180 extracellular domain and five intracellular epitopes were recognized. 7 Further study is required to determine the significance of these findings. Aoyama et al 8 detailed the case of a 33-year-old female and her child with PG, who were followed-up weekly with the BP 180NC16a ELISA.…”