Endemic pemphigus foliaceus, or fogo selvagem, is an autoimmune blistering
skin disease caused by
IgG autoantibodies to a desmosome-associated
glycoprotein. We studied the
IgG subclasses with
autoantibody activity in serum from 29 patients with active disease and in the skin lesions of 18 patients by immunofluorescence, using
IgG-subclass-specific
monoclonal antibodies. The predominant disease
autoantibodies present in all patients were of the
IgG4 subclass.
IgG1 and
IgG2 autoantibodies were detected in low titer in the 29 patients:
IgG1 in 23 patients and
IgG2 in 9.
IgG3 autoantibodies were not detected in the serum of any patient. Direct immunofluorescence testing of skin lesions showed a preferential deposition of
IgG4 on the keratinocyte surface. The pathogenic effect of
IgG4 was demonstrated by the passive transfer of fractions containing
IgG4 autoantibodies from the patients to neonatal BALB/c mice. The disease of the patients was reproduced clinically, histologically, and immunologically in these animals. Only
IgG4 autoantibodies were detected by direct immunofluorescence, bound to the epidermis in the lesions of the mice, and by immunoelectron microscopy at the keratinocyte surface.
IgG4 has previously been reported to be a blocking or protective antibody because it has poor effector functions in vitro, as compared with the other
IgG subclasses. The finding that it is the pathogenic
autoantibody in fogo selvagem raises the possibility that it may also be important in other
autoimmune disease.