Pemphigus foliaceus and pemphigus vulgaris autoantibodies react with the extracellular domain of desmoglein-1.
Pemphigus foliaceus is associated with an autoimmune response against desmoglein-1; however, the fine specificity of these autoantibodies and the role that they play in pathogenesis have not yet been elucidated. In an attempt to develop a system to facilitate the detection and characterization of this antigen/antibody system, recombinant human desmoglein-1 was expressed in COS-1 cells, a mammalian epithelial cell line. The desmoglein-1 transgene product was shown to be expressed on the surface of the COS-1 cells in the appropriate transmembrane orientation. All pemphigus foliaceus sera (endemic form, n = 24; nonendemic form, n = 7) reacted strongly with nonpermeabilized desmoglein-1-transfected cells, exhibiting a punctate cell-surface staining pattern. This reactivity against the desmoglein-1 ectodomain was predominantly an IgG4-restricted response and was calcium dependent. Ten of 18 pemphigus vulgaris sera also reacted with the extra-cellular domain of recombinant desmoglein-1. Use of this eukaryotic expression system should greatly facilitate further characterization of the anti-desmoglein-1 autoimmune response associated with pemphigus foliaceus and pemphigus vulgaris and may aid in determining its pathogenic relevance.
Emery
D J
DJ
Department of Dermatology, Medical College of Wisconsin, Milwaukee 53226.
Diaz
L A
LA
Fairley
J A
JA
Lopez
A
A
Taylor
A F
AF
Giudice
G J
GJ
D000818:Animals; D000937:Antigen-Antibody Reactions; D001323:Autoantibodies / Q000276:immunology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000276:immunology; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008969:Molecular Sequence Data; D010392:Pemphigus / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology
D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C495297:DSG1 protein, human; D051183:Desmoglein 1; D051182:Desmogleins; D051180:Desmoplakins; D007074:Immunoglobulin G; D011994:Recombinant Proteins