Role of intramolecular epitope spreading in pemphigus vulgaris. Clin Immunol 2005 Jul;116(1):54-64
Date
06/01/2005Pubmed ID
15925832DOI
10.1016/j.clim.2005.03.005Scopus ID
2-s2.0-19544373821 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
Pemphigus vulgaris (PV) is an acquired immunobullous disorder. At the early stage of the disease (mucosal PV), patients display only autoimmunity to desmoglein (Dsg) 3 and develop mucosal blisters; while at the later stage of the disease (mucocutaneous PV), patients exhibit non-cross-reactive autoimmunity to both Dsg3 and Dsg1 and acquire cutaneous as well as mucosal blisters. At these two disease stages, Dsg3 autoantibodies exhibit different tissue-binding patterns and pathogenic activities, suggesting that they may recognize distinct epitopes. To test this hypothesis and to investigate the mechanism underlying the disease transition, we studied Dsg3 autoantibody epitopes from mucosal PV patients and patients exhibiting disease transition to mucocutaneous PV. We demonstrated that autoantibodies from the majority of mucosal PV patients target epitopes at the COOH-terminal portion of the Dsg3 ectodomain. Interestingly, only autoantibodies against the Dsg3 NH2-terminal epitope(s) are able to bind human skin. Moreover, we discovered that the intramolecular epitope spreading from Dsg3(87-566) to Dsg3(1-88) is a critical step that precedes the intermolecular epitope spreading from Dsg3 to Dsg1. During disease transition, this mechanism dictates the development of Dsg3 autoantibodies that recognize human skin and lead to expression of cutaneous PV lesions.
Author List
Salato VK, Hacker-Foegen MK, Lazarova Z, Fairley JA, Lin MSMESH terms used to index this publication - Major topics in bold
AutoantibodiesCadherins
Desmoglein 3
Epitopes
Humans
Pemphigus
Peptide Fragments
Protein Structure, Tertiary
Skin