Coexistence of IgA antibodies to desmogleins 1 and 3 in pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus.
BACKGROUND
Pemphigus is a bullous mucocutaneous autoimmune disease characterized by IgG autoantibodies to desmoglein (Dsg) 1 and/or Dsg3. Occasionally direct immunofluorescence of pemphigus skin reveals IgA depositions with an intraepidermal intercellular pattern in addition to the IgG deposition.


OBJECTIVE
To investigate if pemphigus patients, in addition to having IgG autoantibodies, also generate IgA antibodies to Dsg1 and/or Dsg3.


METHODS
Sera of 100 pemphigus patients and 36 bullous pemphigoid controls were tested by IgA enzyme-linked immunosorbent assay (ELISA) to the recombinant extracellular domains of Dsg1 and Dsg3. The patients were selected on clinical grounds and positive IgG ELISA index values for Dsg1 and/or Dsg3. They were divided into four groups: patients having IgG to only Dsg1 (n=34), patients having IgG to both Dsg1 and Dsg3 (n=31), patients having IgG to only Dsg3 (n=27) and patients who had paraneoplastic pemphigus (PNP) (n=8).


RESULTS
IgA antibodies to Dsg1 were found in 13 (38%) of the patients with IgG to Dsg1, in five (16%) of the patients with IgG to both Dsg1 and Dsg3, in four (15%) of the patients with IgG to Dsg3 and in none of the PNP patients. IgA antibodies to Dsg3 were found in one (3%) of the patients with IgG to Dsg1, in 18 (58%) of the patients with IgG to both Dsg1 and 3, in 18 (67%) of the patients with IgG to Dsg3, and in four (50%) of the PNP patients. Immunofluorescence analysis demonstrated intraepidermal intercellular staining IgA antibodies in serum and intercellular IgA deposits in skin of IgA ELISA-positive patients, although to a lesser extent than by ELISA.


CONCLUSIONS
This study shows that in a considerable number of supposedly IgG-mediated pemphigus patients IgA to Dsg1 and Dsg3 is also present. In most cases the antigen specificity of the IgA follows the antigen specificity of the IgG, although in a small number of cases IgA is present against the Dsg not recognized by IgG.
Mentink
L F
LF
Center for Blistering Diseases, Department of Dermatology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
de Jong
M C J M
MC
Kloosterhuis
G J
GJ
Zuiderveen
J
J
Jonkman
M F
MF
Pas
H H
HH
D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D051183:Desmoglein 1 / Q000276:immunology*; D051184:Desmoglein 3 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000276:immunology; D010392:Pemphigus / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D051183:Desmoglein 1; D051184:Desmoglein 3; D007070:Immunoglobulin A; D007074:Immunoglobulin G