As a result of a long-term interest in IgA dermatoses and in the immunopathology of the skin, we have developed a hypothesis that the normal human epidermis may interact with IgA by a receptor mediated mechanism. In preliminary immunoflorescence (IF) studies with use of a rabbit antibody and a monoclonal antibody to the human polymeric immunoglobulin receptor, secretory component (SC), we have identified SC staining along the basement membrane zone of the normal human epidermis. By an immunoprecipitation method for SC, we have identified synthesis by human keratinocytes (HK) of an immunoreactive protein of somewhat higher molecular weight than SC from a transformed colon cell line, HT29 cells. By addition of gamma-interferon, we have been able to stimulate HT29 cells in culture to synthesize SC detectable by direct IF.
Specific aims of this project are as follows: 1) to study the expression of SC by HK, 2) to study in vitro the synthesis of SC by HK, 3) to study the interaction of monomeric and polymeric immunoglobulins with HK, and 4) to study whether abnormalities in skin-associated secretory immune function occur in blistering skin diseases involving IgA as a immunoreactant. The expression of SC by HK will be studied in normal human skin biopsies by direct IF, indirect IF with use of an affinity purified antibody to SC, and by indirect IF with use of a monoclonal antibody to SC. Results will be verified by immunoperoxidase techniques and by immunoelectron microscopy. The in vitro synthesis of SC by HK will be studied by IF and by immunoprecipitation with the affinity purified antibody to SC. The characteristics of immunoreactive SC from HK will be compared to that from HT29 cells. The interaction of purified monomeric IgG and IgA and polymeric IgA and IgM with normal human skin on the nude mouse will be studied by an IF technique. The human skin will be exposed to the immunoglobulin preparation both by injection of the nude mouse and by in vitro incubation. Finally, the immunopathologic characteristics of SC and IgA in the epithelium of the IgA dermatoses, dermatitis herpetiformis and intraepidermal neutrophilic IgA dermatosis, will be compared to normal skin. Synthesis of SC by HK from patients with these disease will be studied in vitro, and the interaction of the HK from these patients with polymeric immunoglobulins will be evaluated and compared to that of HK from normal individuals.
| Huff, J C (1990) Epithelial polymeric immunoglobulin receptors. J Invest Dermatol 94:74S-78S |
