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Date: Tuesday, March 19, 1996 For Release: 5:00 EST Contact: Pat Sheridan/Wayne Little (301)496-4261
Scientists at the National Institutes of Health have identified a protein that is an important marker for Type 1 (juvenile) diabetes, a disease that affects close to one million people in the United States alone. The protein can be used in combination with two other known marker proteins to improve diagnosis of individuals who have diabetes and identify those at risk of developing the disease. This protein and the other marker proteins are also candidates for experimental treatments aimed at preventing the onset of Type 1 diabetes. The identification of the new marker protein, which was reported in today's issue of the Proceedings of the National Academy of Sciences, is part of an ongoing study at the National Institute of Dental Research. Scientists in NIDR's Laboratory of Oral Medicine are investigating the molecular biology of diabetes, a disease known to increase the risk of periodontal (gum) disease and tooth loss.
The research, directed by Drs. Abner Notkins and Michael Lan, focuses on Type 1 diabetes, also known as insulin-dependent diabetes mellitus, or IDDM. The disease develops most often in children and young adults and can account for a variety of severe complications, including blindness, kidney and heart disease, neurologic problems, and premature death.
IDDM is an autoimmune disease in which the immune system produces antibodies that attack the body's own insulin-manufacturing cells in the pancreas. Patients require daily injections of insulin to regulate blood sugar levels.
The destructive antibodies, called autoantibodies, are the basis of the existing diagnostic test for IDDM, which reacts patient serum with sections of human pancreas tissue, a labor-intensive procedure. Recently, however, scientists have been able to identify some of the target proteins in the pancreas that react with the autoantibodies and are using this knowledge to improve disease detection and streamline the screening process.
An earlier study by Dr. Lan and his colleagues identified a marker protein called IA-2 that is present in insulin-producing beta cells of the pancreas and belongs to a family of important regulatory molecules known as tyrosine phosphatases. The study reported today describes a second protein called IA-2 Beta (IA-2 ) that is a member of the same family. The genes for both of the proteins have been cloned and sequenced, and genetically engineered versions of the proteins have been produced in the laboratory.
IA-2 and IA-2 , when used in diagnostic tests, recognized autoantibodies in 70 percent of IDDM patients. Combining IA-2 and IA-2 with a third known marker protein called GAD65, increased the level of identification to 90 percent of individuals with IDDM. Furthermore, the presence of autoantibodies to the marker proteins in otherwise normal individuals was highly predictive in identifying those at risk of ultimately developing clinical disease.
"The identification and production of IA-2 and IA2- make it possible to develop a rapid and effective test that can screen large populations for IDDM," said Dr. Notkins.
"In addition, the proteins are candidates for immune tolerance studies, which attempt to prevent the development of destructive autoantibodies and subsequent disease."
Persons without diabetes also have the marker proteins on their beta cells, but do not make autoantibodies. The scientists are hopeful that the demonstration that IA-2 and IA-2 are major targets of the autoimmune attack will aid in uncovering the actual cause of the disease process.
Investigators on the study were Drs. Jia Lu, Qing Li, Hong Xie, Zhi-Jian Chen, Anna E. Borovitskaya, Abner Louis Notkins, and Michael S. Lan from the Laboratory of Oral Medicine, National Institute of Dental Research; and Dr. Noel K. Maclaren from the University of Florida College of Medicine.