Diabetes antibody best marker so far.

Diabetes antibody best marker so far

Aspecific antibody found in blood from people who eventually developed Type I diabetes might be the best early warning yet for the disease, say researchers at the University of Florida College of Medicine in Gainesville. Called 64K autoantibody, it raises to three the number of known autoantibodies involved in Type I diabetes, which is widely believed to be an autoimmune reaction to the body's own insulin-producing beta cells in the pancreas.

A reliable antibody marker would single out future diabetics, and if it proved to be primary cause of the disease, it could provide the key to therapy that would halt its course before insulin-dependent diabetes occurred. The Florida researchers have found the two previously known antibodies in at most 75 percent of those who later developed the disease. However, the 64K autoantibody has shown up so far in all the subjects who later became diabetic.

These findings, presented in New Orleans this week by Mark Atkinson and his colleagues at the 48th annual meeting of the American Diabetes Association, are based on blood samples drawn from 5,000 schoolchildren and 3,000 close relatives of Type I diabetics selected at random. Twelve have since become diabetic, with all 12 testing positive for the 64Kautoantibody -- so named because it attacks a 64,000-molecular-weight protein on the surface of beta cells. Blood samples taken as early as seven years before the onset of diabetes harbored the 64K autoantibody.

Researchers also tested for the two other Type I-associated antibodies. Insulin antibodies were in the blood of five of the 12 who developed diabetes, and islet-cell antibodies were found in nine.

"We're very sure it's a specific marker," Atkinson says, referring to the 64K autoantibody. He also notes that the antibody's target protein has been found only on beta cells.

Type I is the more acute form of diabetes, usually striking during childhood or adolescence. Insulin injections become routine for these patients, since their bodies do not produce enough of the hormone to control blood-glucose levels. Late-onset diabetes, Type II, often can be controlled with a diet low in sugar.

Atkinson says previous autoantibody studies tested newly diagnosed patients rather than prediabetics. For purposes of comparison, his group also tested newly diagnosed Type I patients, finding 64K autoantibodies in 18 out of 20 patients. None of 18 controls carried the 64K autoantibody.

"Our current studies are isolating and sequencing the surface protein [attacked by the antibody]," Atkinson says. "Our hope is that we could attach toxins to it that would destroy the antibody." He suggests that, being a surface protein, the antibody's target site might be the first in a cascade of reactions that eventually whittle away beta cells.

Atkinson says a toxin specific for the autoantibodies would not have the side effect of suppressing the body's entire immune system, as does cyclosporine, which is currently in clinical trials as a Type I treatment (SN: 11/7/87, p.132). This immunotoxin approach, using the body's immune system as a drug courier, is already under study as a cancer therapy (SN: 4/4/87, p.219). by locking ricin, a plant toxin, onto antibodies that target tumor cells, an immunotoxin can destroy cancer cells without harming other body tissues. The Florida study will be a mirror image of that: The toxin will be attached to the beta-cell surface protein and destroy the antibody when it binds to the cell.

Atkinson predicts his group will begin testing such a therapy in mice later this year. In the meantime, scientists in Denmark also are examining the 64K autoantibody.

The test for 64K autoantibodies currently costs about $500 and takes four to five weeks to process. Atkinson says the assay would have to cost about $2 per test and be much faster to have commercial value.