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Published on: June 17, 2025
Conformational epitope mapping and IgG subclass distribution of desmoglein 3 in paraneoplastic pemphigus
Yuko Futei1, Masayuki Amagai, Takashi Hashimoto
1Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. christy@kp.catv.ne.jp
Background:
Pemphigus vulgaris (PV) shows autoimmune reaction against desmoglein 3 (Dsg3), whereas paraneoplastic pemphigus (PNP) shows autoimmune reaction against Dsg3 as well as numerous members of the plakin family. It has been demonstrated that in PV, dominant epitopes reside in N-terminal adhesive regions of Dsg3 and that the dominant IgG subclass against Dsg3 is IgG4.
Objective:
We attempted to map conformational epitopes and analyze IgG subclass distribution against Dsg3 in PNP.
Method:
Epitopes on Dsg3 for circulating IgG autoantibodies from PNP (n = 22) were studied with competition enzyme-linked immunosorbent assay (ELISA) using domain-swapped molecules between Dsg3 and Dsg1 and were compared with those for IgG autoantibodies from PV (n = 22). IgG subclass distribution was analyzed with PNP serum by Dsg3 ELISA (n = 17).
Results:
Epitopes on Dsg3 in PNP were distributed more broadly through the extracellular domain of Dsg3 than were those in PV, although the N-terminal extracellular domains of Dsg3 were more frequently recognized than the C-terminal extracellular domains. IgG subclass in PNP was IgG1 and IgG2 dominant.
Conclusion:
Autoimmune response against Dsg3 in PNP is more diversified than that in PV, a finding that suggests PNP and PV have different pathophysiologic mechanisms for triggering production of anti-Dsg3 IgG.
