DERMATITIS HERPETIFORMIS & THE MUCOSAL IMMUNE RESPONSE

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Dermatitis herpetiformis (DH) is a blistering skin disease with characteristic cutaneous deposits of IgA and an associated gluten sensitive enteropathy (GE). In addition, clinical improvement is noted when DH patients adhere to a gluten-free diet. These findings suggest that the mucosal immune response may play a central role in the pathogenesis of DH. The purpose of this project will be to determine the relationship between the gut and the skin in DH and to evaluate the mucosal immune response of DH patient and normal individuals. To accomplish this we will: 1) elute IgA from the skin of patients with DH, determine the subclass of the eluted IgA and assess its ability to bind to normal human skin, 2) identify and characterize the antigen in DH skin which binds IgA and determine if that antigen is present in normal human skin, 3) assess the ability of IgA from serum, secretions, and isolated immune complexes to bind to the isolated antigen, 4) evaluate the mucosal immune response, in both serum and secretions, in patients with DH to previously encountered dietary antigens as well as to a previously unencountered antigen, KLH. Keratome sections of DH skin and normal human skin will be treated with buffers which are capable of eluting immune complexes from tissue and of solubilizing the dermal-epidermal junction. The eluates obtained will then be analyzed by enzyme linked immunoadsorbent assay (ELISA) for total IgA and IgA subclass composition. The eluates will also be analyzed using SDS-PAGE and immunoblot to detect the antigen to which IgA binds. These immunoblots will be reacted with IgA from serum, secretions, and isolated IgA containing circulating immune complexes from both normal individuals and DH patients. The mucosal immune response of these patients will also be evaluated by measuring both serum and secretory antibodies against gliadin, and other dietary antigens using ELISA. These antibodies will be characterized as to immunoglobulin class and IgA subclass. The ability of patients to respond to a new antigen, KLH, will be determined by feeding patients and normal individuals KLH and assessing the serum and secretory antibody respsne by ELISA. The relationship between secretory and systemic immunity will be investigated by attempting to immunize these same indivduals by subcutaneous injection after enteric immunization and assessment of the antibody response. These studies will provide insights into the basic pathophysiology of DH, and increase our understanding of the mucosal immune response in patients with abnormal intestinal morphology (DH with GSE) and in normal individuals.