A novel ELISA reveals high frequencies of BP180-specific IgE production in bullous pemphigoid.

Bullous pemphigoid (BP) is a humoral autoimmune disease directed predominantly against the non-collagenous NC16A domain of the BP180 hemidesmosomal protein. Our laboratory has recently shown, using a mouse xenograft model, that passive transfer of IgE autoantibodies from BP sera induces a skin phenotype that recapitulates the early phases of the disease. Herein, we describe the development of a highly specific and sensitive ELISA to detect circulating IgE autoantibodies that recognize BP180-NC16A. Using this assay, we detected NC16A-specific IgE-class autoantibodies in 77% of BP sera. This frequency, which is significantly higher than reported previously, is comparable to that of anti-NC16A IgG autoantibody production. In 3 BP patients monitored over time, the circulating NC16A-specific levels of both IgE and IgG were associated with clinical disease activity; however, patient sera did not always contain high levels of both isotypes. In conclusion, our ELISA provides a highly sensitive and specific tool for the detection of BP180-specific IgE in patient sera. Furthermore, we report that the majority of BP sera contain both IgE and IgG class autoantibodies specific for NC16A and suggest that screening for both isotypes of autoantibodies may provide a better diagnostic value than IgG alone.