title: Demonstration of epitope-spreading phenomena in bullous pemphigoid: results of a prospective multicenter study.
abstract: Bullous pemphigoid (BP), the most common autoimmune subepidermal bullous disease, is associated with an autoantibody response to BP180 and BP230, two components of junctional adhesion complexes in human skin promoting dermo-epidermal cohesion. Retrospective analyses demonstrated that these autoantigens harbor several epitopes targeted by autoaggressive B and T cells. The aim of this prospective multicenter study was to assess the evolution of IgG autoantibodies in 35 BP patients over a 12-month observation period. Epitope-spreading (ES) events were detected in 17 of 35 BP patients (49%). They preferentially occurred in an early stage of the disease and were significantly related to disease severity at diagnosis. Moreover, in three patients, spreading of IgG reactivity to intracellular epitopes of BP180 and BP230 was preceded by recognition of the BP180 ectodomain. Finally, IgG reactivity with extracellular epitopes of BP180 and intracellular epitopes of BP230 correlated with the severity of BP in disease course. These findings support the idea that IgG recognition of the BP180 ectodomain is an early and crucial event in BP disease, followed by variable intra- and intermolecular ES events, which likely shape the individual course of BP.
authors.affiliation: Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Italy. g.dizenzo@idi.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Zenzo
authors.forename: Sybille
authors.initials: S
authors.lastname: Thoma-Uszynski
authors.forename: Valentina
authors.initials: V
authors.lastname: Calabresi
authors.forename: Lionel
authors.initials: L
authors.lastname: Fontao
authors.forename: Silke C
authors.initials: SC
authors.lastname: Hofmann
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lacour
authors.forename: Francesco
authors.initials: F
authors.lastname: Sera
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Luca
authors.initials: L
authors.lastname: Borradori
authors.forename: Michael
authors.initials: M
authors.lastname: Hertl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000276:immunology; D002352:Carrier Proteins; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins; D018450:Disease Progression; D000071821:Dystonin; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008137:Longitudinal Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens / Q000276:immunology; D010391:Pemphigoid, Bullous / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D012720:Severity of Illness Index; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human