No involvement of IgG autoantibodies against extracellular domains of desmoglein 2 in paraneoplastic pemphigus or inflammatory bowel diseases.
BACKGROUND
Patients with paraneoplastic pemphigus (PNP) and inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), develop autoantibodies against simple epithelial cells. About 20-30% of patients with PNP develop fatal bronchiolitis obliterans, in which autoantibody-mediated injury is suspected because of in vivo IgG deposition on cell surfaces of bronchial epithelia.


OBJECTIVE
The purpose of this study is to determine whether patients with PNP, CD and UC have IgG autoantibodies against desmoglein 2 (Dsg2), which is expressed in all desmosome-bearing cells including respiratory and intestinal epithelia.


METHODS
A secreted form of recombinant Dsg2 (rDsg2-His) which contains its entire extracellular domains was produced by baculovirus expression. The reactivity of patients' sera against rDsg2-His was examined by ELISA as well as immunoprecipitation.


RESULTS
An anti-Dsg2 mouse monoclonal antibody, 6D8, showed positive reactivity against rDsg2-His in both methods. However, none of 38 PNP sera reacted with rDsg2-His by ELISA and none of 15 PNP sera tested immunoprecipitated rDsg2-His. Furthermore, none of 12 CD or 27 UC sera reacted with rDsg2-His by ELISA.


CONCLUSIONS
These findings indicate that IgG autoantibodies against Dsg2 are not involved in PNP, CD or UC and suggest the existence of other unknown cell surface target antigen(s) in bronchiolitis obliterans in PNP.
Ota
Takayuki
T
Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, 160-8582, Tokyo, Japan. ohta@sc.itc.keio.ac.jp
Amagai
Masayuki
M
Watanabe
Mamoru
M
Nishikawa
Takeji
T
D001323:Autoantibodies / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology*; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D010257:Paraneoplastic Syndromes / Q000276:immunology*; D010392:Pemphigus / Q000276:immunology*; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary
D001323:Autoantibodies; D003598:Cytoskeletal Proteins; C495314:DSG2 protein, human; D051301:Desmoglein 2; D051182:Desmogleins; D051180:Desmoplakins; D007074:Immunoglobulin G