Overlapping distribution of autoantibody specificities in paraneoplastic pemphigus and pemphigus vulgaris

Paraneoplastic pemphigus is an autoimmune bullous skin disease in which autoantibodies immunoprecipitate a characteristic antigenic complex. The objective of this study was to analyze by immunoblotting and immunoelectron microscopy the autoimmune response in five patients with clinical and immunohistologic features typical of paraneoplastic pemphigus. In a first series of experiments, immunoblotting and immunoelectron microscopy were performed using anti-human whole Ig. Although immunoblotting results were consistent with the autoantibody specificities previously described in paraneoplastic pemphigus sera, immunoelectron microscopy demonstrated the presence of Ig deposits on desmosomal plaques, on hemidesmosomes and, surprisingly, on both the extracellular part of desmosomes and the keratinocyte plasma membrane. In a second series of experiments, immunoblotting and immunoelectron microscopy were carried out using antihuman IgG subclasses. The major observation was that two sera contained, in addition to the anti-desmoplakins I-II, anti-185-kD and anti-230-kD autoantibodies, autoantibodies that stained the desmoglea by indirect immunoelectron microscopy and bound to a 130-kD polypeptide by immunoblotting. One serum was particularly demonstrative: IgG1 bound to the 250- and 220-kD bands corresponding to desmoplakins I and II on immunoblots and to the desmosomal plaques of keratinocytes in immunoelectron microscopic preparations; IgG3 recognized a 185-kD immunoblotting band and hemidesmosomes and desmosomal plaques by immunoelectron microscopy; IgG4 bound to the 130-kD immunoblotting band of pemphigus vulgaris and labeled the desmoglea and the keratinocyte plasma membrane by immunoelectron microscopy. These results demonstrate that the paraneoplastic-pemphigus autoimmune response involves both intracellular and extracellular desmosomal antigens and suggest an overlapping distribution of autoantibody specificities among autoimmune bullous skin diseases.