IgE autoantibodies in bullous pemphigoid: supporting role, or leading player?

Bullous pemphigoid (BP) is a common autoimmune blistering skin disease in which two hemidesmosomal components--the transmembrane collagen XVII (BP180 or BPAG2) and the plakin family protein BP230 (BPAG1)--are targeted by autoimmunity. Of these, collagen XVII (COL17) is thought to be a major autoantigen, and vital roles of IgG autoantibodies in blister formation have been elucidated. However, BP shows distinct features, including pruritic urticarial erythema and eosinophilic infiltration, which may be independent of IgG-mediated autoimmunity. Recently, it has been revealed that sera from certain patients with BP contain IgE autoantibodies to COL17 and that IgE autoantibodies bind to peri-lesional dermal-epidermal junctions. Mouse models have demonstrated that IgE antibodies to COL17 induce erythema and eosinophilic infiltration in skin. In addition, the successful treatment of severe BP with omalizumab, a humanized monoclonal antibody targeting IgE, has been reported. These findings suggest that both IgG and IgE autoantibodies to COL17 may be involved in the BP pathogenesis. This article summarizes IgE-mediated autoimmunity to COL17 in BP.