Weill Cornell Medical College Advances
The Immune Deficiency Causing Type 1 Diabetes

EDITED By HERMAN ROSEN, M.D.

An article recently published in the Journal of Clinical Investigation by lead authors Drs. Noel Maclaren and Anjli Kukreja of the Department of Pediatrics at Weill Cornell Medical College investigates 60 patients with immune-mediated type 1 diabetes. The study addresses what predisposes to this condition, and the latest measures for diagnosis and therapy. The authors suggest a new strategy for combating the disease: stimulate rather than suppress the patient’s immune system.

In immune-mediated diabetes, a genetic predisposition to autoimmunity destroys the pancreatic beta cells that secrete insulin. Type 1 diabetes can also occur, less commonly, without autoimmunity. Insulin therapy is always required in type 1 diabetes, which accounts for about 10 percent of all diabetics.

In all their subjects, the authors found a deficiency in certain kinds of white blood cells, called T regulatory cells, because they regulate the immune system and protect the body from being attacked by its own defenses.

The deficiency is an absolute requirement for immune-mediated diabetes, but not everyone with the deficiency will develop the condition, but may develop other autoimmune diseases, such as thyroiditis, Addison’s disease, vitiligo or multiple sclerosis.

Testing for this defect in T regulatory cells is useful in diagnosing the immune form of type 1 diabetes, and predicting whether a relative might develop it. First, the family member is tested for antibodies to their own islet cells. If the test is positive it indicates that the person is progressing toward diabetes, but not necessarily clinical disease. Then the family member is tested for T regulatory cells. Finding a deficiency at this time is strongly predictive that type 1 diabetes will occur.

For years, physicians have tried to treat this autoimmune disease by suppressing the immune system, and results have been disappointing. The need for insulin persists and suppression of the immune system predisposes to various infectious and malignant diseases. However, results of this study suggest a new therapeutic strategy: instead of suppressing the immune system, stimulate a select part of it, the T regulatory cells.

To accomplish this stimulation of T regulatory cells, the authors point to a substance, alpha-galactosylceramide, found in sea sponges near Japan, which has turned out to be such an immunostimulant. Reports of its trials in non-obese diabetic mice have been encouraging say the authors. They suggest human trials of synthetic forms of the stimulant soon.#
Dr. Herman Rosen is Clinical Professor of Medicine at Weill Cornell Medical College.

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