Pemphigus is categorized as an autoimmune bullous disease described by the presence of autoantibodies against adhesion molecules, desmogleins, and desmocollins (DSCs). 

The pathogenicity of anti-DSC3 antibodies in pemphigus is well known but not its characteristics. So a study analyzed its characteristics using DSC3 domain-swapped desmoglein 2 molecules where the prosequence and five extracellular (EC) domains of desmoglein 2 were substituted with the corresponding domains of human DSC3.  These proteins were used to establish an ELISA and analyze sera from 56 patients with pemphigus. 

The observations of the study were as follows-

• 34 pemphigus sera were positive for DSC3 full-EC domains, among which 44.1% were positive for the EC2 domain, while others were rarely positive.
• The reactivity to a calcium-dependent epitope in DSC3 by ELISA was evaluated with EDTA.
• EDTA compromised the reactivity with the EC2 domain.
• In vitro assay demonstrated, IgG from patients with paraneoplastic pemphigus preadsorbed with EC2 prevented the reduction of DSC3 and keratinocyte dissociation contrasting that of EDTA-treated EC2. 

Thus the study explained a predominant recognition of calcium-dependent epitopes in the EC2 domain by anti-DSC3 antibodies and its pathogenicity on keratinocyte adhesion through DSC3 depletion.

Source: Koga H, Teye K, Otsuji Y, Ishii N, Hashimoto T, Nakama T. Autoantibodies to DSC3 in Pemphigus Exclusively Recognize Calcium-Dependent Epitope in Extracellular Domain 2, JID,2021;141(9):2123-2131. DOI:https://doi.org/10.1016/j.jid.2021.01.032