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