IgE antibodies in sera from patients with bullous pemphigoid are autoantibodies preferentially directed against the 230-kDa epidermal antigen (BP230)

Bullous pemphigoid (BP) is unique among autoimmune skin diseases in which a high serum IgE level has been detected. We sought to determine the antigenic specificity of these IgE antibodies in 39 BP sera by immunofluorescence microscopy, immunoblot, and ELISA. The patient's sera contained IgG antibodies to 230-kDa (BP230) (n = 20), 180-kDa (BP180) (n = 9), and both BP230 and BP180 (n = 10) antigens. Serum IgE levels varied from 29 to 5000 kIU/L (mean +/- SD, 856 +/- 1426 kIU/L), among which sera containing IgG antibodies to BP230 had an IgE level on average 4.3 times higher than anti-BP180 sera. IgE antibodies in 18 sera were found to be autoantibodies reactive either with an epidermal component of basement membrane zone by immunofluorescence microscopy on 1 M NaCl-split skin or with a 230-kDa antigen by immunoblots of cultured human keratinocytes. The 230-kDa epidermal antigen recognized by IgE antibodies comigrated with the BP230 as labeled by a specific human monoclonal antibody. IgE anti-BP230 antibodies in patients' sera were always associated with IgG autoantibodies. No sera contained IgE antibodies to BP180 or to any other epidermal or dermal antigens as verified by immunoblot and ELISA. A good correlation was found between the presence of IgE circulating autoantibodies and the level of serum IgE (P < 0.004). IgE antibodies to BP230, like IgG autoantibodies, were mapped primarily to the C-terminal end of the protein, as they labeled rBP55, a BP230 recombinant protein encoded by a cDNA for the C-terminal end of BP230.