Endemic pemphigus foliaceus or Fogo Selvagem (FS) is an autoimmune blistering
skin disease mediated by
autoantibodies directed against components on the surface of subcorneal keratinocytes. All patients have high titers of these
autoantibodies in the
IgG4 subclass as determined by indirect immunofluorescence on frozen skin sections. In addition, patients may also have
autoantibodies in other
IgG subclasses, particularly
IgG1, but the titers in these subclasses are significantly lower than those found in the
IgG4 subclass. We have now found that in addition to isotype preference,
autoantibodies from FS patients show clonal restriction as evidenced by oligoclonal banding on isoelectric focusing after probing with extracts from both human and bovine epidermis. Both
IgG1 and
IgG4 exhibit oligoclonal banding, but the distribution of these bands in the pH gradient differs for these two subclasses. Whereas the
IgG4 oligoclonal bands are distributed throughout the
IgG4 pH range,
IgG1 banding appears to be concentrated in the more basic region of the
IgG1 pH range. This finding suggests that the
IgG1 autoantibodies have undergone selective somatic mutation by a negatively charged
autoantigen. Similar findings have been reported for pathogenic
DNA autoantibodies associated with SLE. The wide distribution of
IgG4 banding suggests that this response may have followed the
IgG1 response and has not undergone selective mutation. Both
IgG1 and
IgG4 appear to be Ca++ dependent
autoantibodies.