Immune response towards the amino-terminus of desmoglein 1 prevails across different activity stages in nonendemic pemphigus foliaceus.

Abstract

BACKGROUND:

Pemphigus foliaceus (PF) is a blistering skin disease mediated by antibodies to desmoglein (Dsg) 1. The two major subtypes are nonendemic and endemic PF. A previous study in endemic PF demonstrated that changes in antibody epitope could modulate disease relapse and remission.

OBJECTIVES:

To characterize the frequency of immunoreactivity to various Dsg1 extracellular (EC) domains in nonendemic PF and to study if there is any change in epitope profile across various activity stages.

METHODS:

Sera from 34 patients with nonendemic PF were selected. To map the conformational epitopes by immunoprecipitation-immunoblotting, we constructed five Dsg1/Dsg2 domain-swapped molecules, with each molecule representing one EC domain of Dsg1 on a backbone of Dsg2.

RESULTS:

Dsg1 EC1, EC2, EC3, EC4 and EC5 domains were recognized by 88%, 50%, 13%, 22% and 0% of active PF sera, respectively. Immunoreactivity to EC3 or EC4 often cosegregated with that to either EC1 or EC2. Longitudinal follow-up of 21 patients with PF for a median of 16 months revealed that, in most cases, immunoreactivity to the amino-terminus of Dsg1 persisted across various activity stages; only two patients lost their EC1 reactivity upon remission and changed their major epitope(s) to EC2 ± EC3.

CONCLUSIONS:

Most of the anti-Dsg1 antibodies in nonendemic PF bind to the amino-terminus of Dsg1, a region critical for intercellular adhesion of cadherins, and this skewed amino-terminal immunoreactivity prevails across various activity stages in most patients, even upon remission. These findings are valuable for understanding the biology of Dsg-mediated cellular adhesion as well as for the development of epitope-based monitoring and therapeutic strategies.

• Authors: P T Chan, B Ohyama, K Nishifuji, K Yoshida, K Ishii, T Hashimoto, M Amagai
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 162 Issue 6 Pg. 1242-50 (Jun 2010) ISSN: 1365-2133 [Electronic] England
• PMID: 20163417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 The Authors. Journal Compilation © 2010 British Association of Dermatologists.

Chemical References

• Autoantibodies
• Desmoglein 1
• Desmoglein 2
• Epitopes
• Recombinant Proteins

Topics

• Autoantibodies (immunology)
• Desmoglein 1 (chemistry, immunology)
• Desmoglein 2 (chemistry, immunology)
• Enzyme-Linked Immunosorbent Assay
• Epitopes (immunology)
• Follow-Up Studies
• Humans
• Immunoblotting
• Immunoprecipitation
• Pemphigus (blood, immunology, physiopathology)
• Recombinant Proteins (immunology, metabolism)
• Severity of Illness Index