title: 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.
authors.affiliation: Molecular and Cell Biology Laboratory, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Zenzo
authors.forename: Valentina
authors.initials: V
authors.lastname: Calabresi
authors.forename: Fabiana
authors.initials: F
authors.lastname: Grosso
authors.forename: Marzia
authors.initials: M
authors.lastname: Caproni
authors.forename: Marina
authors.initials: M
authors.lastname: Ruffelli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology*; D001666:Binding Sites, Antibody; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes; D005110:Extracellular Space / Q000276:immunology*; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D007425:Intracellular Membranes / Q000276:immunology*; D024041:Non-Fibrillar Collagens; D006559:Pemphigoid Gestationis / Q000097:blood / Q000276:immunology*; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D012189:Retrospective Studies; D000097805:Collagen Type XVII
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII