The general and long-term goal of my laboratory is to study autoantibody-mediated skin diseases in order to further our understanding not only of the pathophysiology of these diseases but also of the structure and function of normal epidermis and epidermal basement membrane zone. Specifically, antibodies in these diseases define molecules in the normal epidermis. We have characterized the antigens defined by three of these diseases: bullous pemphigoid (BP), pemphigus vulgaris (PV), and pemphigus foliaceus (PF). We have defined the cells which synthesize these antigens, as well as the antigen defined by the autoantibodies found in patients with epidermolysis bullosa acquisita (EBA). We have used the binding of antibodies to specific molecules to make diagnoses of BP, EBA, PV or PF in various complicated cases of these diseases. We have demonstrated that PF autoantibodies can cross the placenta and bind to fetal skin without causing disease in the newborn. We have demonstrated that PF antibodies bind a protein (desmoglein I) found in desmosomes, and define a calcium- sensitive epitope on a desmosomal protein complex. Thus, PF is an autoimmune disease in which the antibody target is the desmosome. We have demonstrated that antibodies from all PF patients bind a unique complex of proteins that is distinct from the complex bound by PV antibodies. Although the PV antigen complex is distinct from the PF antigen complex, the two complexes share certain biochemical similarities. For example, both complexes have a common 85 D polypeptide chain which binds to a 160 kD (PF) or 130 kD (PV) polypeptide. The latter two polypeptides have identical isoelectric points. Using a lambda gtll expression library, we have isolated a cDNA clone that synthesizes part of the BP antigen. We have used this BP clone to show that the mRNA encoding BP antigen is about 9 kb. We have also deduced the peptide sequence of the C-terminal end of the molecule.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Biology And Diagnosis (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB003667-05
Application #
3916267
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code