Epitope analysis of antidesmoglein 1 autoantibodies from patients with pemphigus foliaceus across different activity stages. (1st November 2015) - Kamiya, K.
Summary: Background: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are closely related, but clinically distinct, autoimmune blistering diseases caused by autoantibodies against desmoglein (Dsg)1 and Dsg3, respectively. Using ethylenediaminetetraacetic acid (EDTA)‐treated Dsg3 enzyme‐linked immunosorbent assay (ELISA) we have shown that the proportion of anti‐Dsg3 antibodies against calcium‐dependent epitopes decreased upon shifting to the inactive phase in patients with PV. Objectives: To analyse the epitope profiles of anti‐Dsg1 antibodies across the different activity stages of PF. Methods: We evaluated five patients with PF who retained high serum levels of anti‐Dsg1 antibodies in the inactive phase. Sera were obtained in both the active and inactive phases, and were analysed by EDTA‐treated and exfoliative toxin‐treated ELISAs. To map the epitopes of anti‐Dsg1 antibodies, immunoprecipitation–immunoblotting was performed using a set of Dsg1/Dsg2 domain‐swapped molecules. Results: Anti‐Dsg1 antibodies against the calcium‐dependent epitopes of Dsg1 were the predominant antibodies in both the active and inactive phases. The proportion of anti‐Dsg1 antibodies against the calcium‐dependent epitopes did not change upon shifting to the inactive phase. The results of immunoprecipitation–immunoblotting showed that most of the anti‐Dsg1 antibodies bound to the extracellular domains (EC)1–2 of Dsg1. Conclusions: In patients with PF, the calcium‐dependent epitopes on EC1 and EC2 of Dsg1 contained definitively pathogenic and nonpathogenic epitopes. The disease activity might be differentially controlled by the antibodies between PF and PV depending on the presence or absence of the nonpathogenic epitope. Abstract : What's already known about this topic? The titres of serum antidesmoglein (anti‐Dsg) antibodies generally correlate with the disease activity of pemphigus, but some patients have nonpathogenic serum anti‐Dsg antibodies. Using ethylenediaminetetraacetic acid (EDTA)‐treated Dsg3 enzyme‐linked immunosorbent assay (ELISA) we have confirmed in patients with pemphigus vulgaris that the pathogenicity of anti‐Dsg3 serum antibodies is determined mainly by the amount of anti‐Dsg3 antibodies against the calcium‐dependent epitopes of Dsg3. What does this study add? We have established EDTA‐treated Dsg1 ELISA and exfoliative toxin‐treated Dsg1 ELISA based on the structural characteristics of Dsg1. Most of the anti‐Dsg1 antibodies bound to the calcium‐dependent epitopes on the extracellular domains (EC)1–2 of Dsg1 in both the active and inactive phases of pemphigus foliaceus (PF). In PF, both pathogenic and nonpathogenic epitopes of anti‐Dsg1 antibodies are located in the EC1–2 domains of Dsg1. Linked Comment: Hammers and Stanley, Br J Dermatol 2016 ; 174: 17–18 .