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.


METHODS
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.


CONCLUSIONS
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.
Futei
Yuko
Y
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. christy@kp.catv.ne.jp
Amagai
Masayuki
M
Hashimoto
Takashi
T
Nishikawa
Takeji
T
D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D015820:Cadherins / Q000276:immunology*; D051184:Desmoglein 3; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D010392:Pemphigus / Q000276:immunology*
D001323:Autoantibodies; D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D007074:Immunoglobulin G