A role for autoimmunity in the development of islet cell destruction has been demonstrated in Type I diabetes. DeCamilli and co-workers have recently demonstrated in rare Type I diabetics anti-neuronal (anti-GAD) antibodies associated with the neurologic stiff-man syndrome. Recent studies in my laboratory have demonstrated complement fixing autoantibodies directed against adrenal medulla, sympathetic ganglia, and vagus nerve in pre-type I diabetes and patients with clinically overt Type I diabetes. We have also demonstrated a lymphocytic infiltrate in the adrenal medulla of Type I diabetics who died early in the disease and a duration dependent fibrosis of the adrenal medulla in long standing Type I diabetics. Pilot studies suggest a correlation between autoantibodies and autonomic dysfunction. In the current proposal the following hypotheses will be tested: 1. Type I diabetic subjects anti-adrenal medullary, anti-sympathetic ganglia and/or unit-vagus nerve antibodies are associated with the development of cardiovascular autonomic dysfunction and impaired glucose counter-regulation. This hypothesis will be tested by evaluating glucose counter-regulatory function and cardiovascular autonomic function prospectively in Type I diabetic subjects with and without the autoantibodies noted above. 2. Characterization of the adrenal medullary, sympathetic ganglia, and vagus nerve antigen(s). Glycoconjugates in the form of both glycoproteins and glycolipids (gangliosides) have been described as neuroendocrine antigenic targets in autoimmune glandular illness. It is expected that characterization of the adrenal medullary and sympathetic ganglia antigens may show structural similarity to the antigens already described in polyglandular autoimmune illnesses and should lead to novel autoantibody assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI030987-02
Application #
3145962
Study Section
Pathology A Study Section (PTHA)
Project Start
1990-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Joslin Diabetes Center
Department
Type
DUNS #
071723084
City
Boston
State
MA
Country
United States
Zip Code
02215
Rabinowe, S L (1990) Immunology of diabetic and polyglandular neuropathy. Diabetes Metab Rev 6:169-88