IgG4 and IgE are the major immunoglobulins targeting the NC16A domain of BP180 in bullous pemphigoid: Serum levels of these immunoglobulins reflect disease activity

Background: Bullous pemphigoid (BP) is an autoimmune blistering disease ass ociated with autoantibodies against the hemidesmosomal glycoprotein BP180. The noncollagenous (NC)16A domain of BP180 has recently been shown to harbo r major antigenic sites recognized by BP sera. Objective: The purpose of this study was to characterize the subclass distr ibution and fine specificities of autoantibodies to BP180 NC16A present in the circulation of patients with BP before, and during the course of, thera py for this disease. Methods: Eighteen BP sera were analyzed by immunoblotting and enzyme-linked immunosorbent assay for the presence of IgG1, IgC2, IgG3, IgG4, and IgE re active with various sites on the BP180 NC16A domain. The sera were collecte d before treatment was started and at 4- and 8-week time points after initi ation of treatment. Results: We identified IgG4 and IgE as the major immunoglobulins that prefe rentially react with two distinct epitopes (MCW-1 and MCW-2) within BP180 N C16A. Levels of these autoantibodies correlated with disease activity in BP . During the course of disease, no change was observed with regard to the i mmunoglobulin subclass predominantly reacting with BP180 NC1GA or the speci fic epitopes within this domain. Conclusion: Our data demonstrate that remission of BP is paralleled by a de crease of serum levels of IgE and the different IgG subclasses reactive wit h BP180 NC16A.