Conformational epitope mapping and IgG subclass distribution of desmoglein 3 in paraneoplastic pemphigus.
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.[1]References
- Conformational epitope mapping and IgG subclass distribution of desmoglein 3 in paraneoplastic pemphigus. Futei, Y., Amagai, M., Hashimoto, T., Nishikawa, T. J. Am. Acad. Dermatol. (2003) [Pubmed]
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