Immunolocalization of target autoantigens in IgA pemphigus.

IgA pemphigus is a rare autoimmune bullous disease characterized by IgA deposition at keratinocyte cell surfaces. Clinically and histologically, IgA pemphigus is divided into two major subtypes: subcorneal pustular dermatosis (SPD) type and intraepidermal neutrophilic IgA dermatosis (IEN) type. Using cDNA transfection and living cell immunofluorescence, we previously showed that desmocollin 1, one of the desmosomal cadherins, is the autoantigen in SPD-type IgA pemphigus, but the autoantigen in IEN type is still unclear. In the present study we investigated antigen localization by postembedding immunoelectron microscopy. We examined three sera each of SPD-type and IEN-type IgA pemphigus. In SPD-type, gold particles were observed predominantly in the extracellular spaces between keratinocytes at desmosomes, although a few particles were observed in the intracellular domain at the desmosomal attachment plaques. In IEN type, the gold particles were observed mainly in the intercellular spaces in nondesmosomal areas. These results provide evidence that the IgA in the sera of SPD-type IgA pemphigus reacts with the extracellular domain of desmocollins. In contrast, the autoantigen for IEN type may in fact not be a component of desmosomes. IEN-type IgA pemphigus may be the first member of the pemphigus group of autoimmune bullous dermatoses that reacts with a nondesmosomal transmembranous protein.