The Role of IgE Anti–Basement Membrane Zone Autoantibodies in Bullous Pemphigoid

Abstract

Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the hemidesmosomal protein BP180 (BPAg2, type XVII collagen). NC16A, a noncollagenous stretch of the BP180 ectodomain, is the primary target of pathogenic IgG autoantibodies and IgE class autoantibodies. This study further characterized the IgE-reactive regions of BP180. Of ten sera from untreated BP patients, eight contained IgE reactive with the entire BP180 ectodomain. The IgE in 4 of these 8 sera reacted with NC16A, while in the remaining 4 sera IgE immunoreactivity was restricted to sites downstream of NC16A. In contrast, IgG reactivity to NC16A was detected in 9 of the 10 BP sera, and in the remaining serum, IgG, as well as IgE, reacted exclusively with non-NC16A sites on the BP180 ectodomain. Fine mapping of the antigenic sites within NC16A revealed very similar reactivity patterns for IgE and IgG, with NC16A subregion-2 being the major site recognized by both isotypes. Eight of the untreated BP patients were tested for histamine release from their basophils in response to NC16A. Antigen-specific histamine release was observed only in those patients with detectable circulating IgE directed against NC16A (3 of 8). Future studies will investigate the pathogenic relevance of anti-BP180 IgE.