Journal article
Role of intramolecular epitope spreading in pemphigus vulgaris
Clinical immunology (Orlando, Fla.), Vol.116(1), pp.54-64
2005
DOI: 10.1016/j.clim.2005.03.005
PMID: 15925832
Abstract
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 NH
2-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.
Details
- Title: Subtitle
- Role of intramolecular epitope spreading in pemphigus vulgaris
- Creators
- Valerie K. Salato - Medical College of WisconsinMary K. Hacker-Foegen - Medical College of WisconsinZelmira Lazarova - Medical College of WisconsinJanet A. Fairley - Medical College of WisconsinMong-Shang Lin - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Clinical immunology (Orlando, Fla.), Vol.116(1), pp.54-64
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.clim.2005.03.005
- PMID
- 15925832
- ISSN
- 1521-6616
- eISSN
- 1521-7035
- Language
- English
- Date published
- 2005
- Academic Unit
- Dermatology
- Record Identifier
- 9984296309602771
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