Absorption of pathogenic autoantibodies by the extracellular domain of pemphigus vulgaris antigen (Dsg3) produced by baculovirus.
Pemphigus vulgaris (PV) is an autoimmune blistering disease, in which autoantibodies against PV antigen (PVA or Dsg3) play a pathogenic role in inducing blister formation. Bacterial fusion proteins of PVA failed to absorb pathogenic autoantibodies from PV patients' sera probably because they did not represent the proper conformation. Therefore, a chimeric protein, PVIg, consisting of the whole extracellular domain of PVA and the constant region of human IgG1, was produced in either in COS7 or in insect Sf9 eucaryotic cells. Both PVIg-COS7 and PVIg-Sf9 were recognized by all of the 35 PV sera tested, but not by any of 10 pemphigus foliaceus (PF), 16 Brazilian PF, 10 bullous pemphigoid, or five normal control sera. Incubation of PV patients' sera with PVIg-Sf9 removed heterogeneous autoantibodies and significantly reduced their immunofluorescence titers on normal human epidermis, although PVIg-Sf9 did not affect the titers of PF sera at all. Furthermore, PVIg-Sf9 absorbed pathogenic autoantibodies from patients' sera and prevented gross blister formation in a neonatal mouse model for pemphigus. These results indicate that this baculovirus product has the proper conformation of the authentic PVA and that its conformation is important in pathogenicity of pemphigus.
Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
M
M
Amagai
T
T
Hashimoto
N
N
Shimizu
T
T
Nishikawa
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D015820:Cadherins / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D051184:Desmoglein 3; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008969:Molecular Sequence Data; D010392:Pemphigus / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D015820:Cadherins; C071894:DSG3 protein, human; D051184:Desmoglein 3; D007074:Immunoglobulin G; D011994:Recombinant Proteins