Mom's antibodies may help trigger type 1 diabetes

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Mom's antibodies may help trigger type 1 diabetes

By Amy Norton

NEW YORK, Apr 02 (Reuters Health) - The seeds of type 1 diabetes could

in some cases rest in antibodies passed from mother to infant, new

research in mice suggests.

The findings stand in contrast to what has been believed about the

abnormal immune response that causes type 1 diabetes--and suggest that

this " paradigm should now be re-evaluated, " according to some experts.

Moreover, if the mouse findings can be extended to humans, it could

become possible to prevent certain cases of early childhood type 1

diabetes, said Dr. Matthias von Herrath of La Jolla Institute for

Allergy and Immunology in San Diego, California.

However, he told Reuters Health, it has not yet been shown that the

transfer of maternal antibodies can trigger type 1 diabetes in children.

In fact, the prevailing wisdom has been that antibodies play no role in

causing the disease, according to von Herrath, who wrote an editorial

published with the new study in the April issue of Nature Medicine.

Type 1 diabetes occurs when the pancreas no longer produces insulin, a

hormone key in moving sugars from the blood and into cells to be used

for energy. The disease arises from an aberrant immune system assault on

the pancreatic cells that churn out insulin. Exactly what triggers this

response--known as an autoimmune reaction--is unclear, but experts have

believed that T cells are the part of the immune system where it all

goes awry. T cells are key immune cells that normally destroy foreign

invaders.

Antibodies are proteins produced by the immune system that latch onto

foreign substances and mark them for destruction. And although

individuals in the pre-diabetes stages have been found to harbor

antibodies against their own insulin-producing cells, the antibodies

themselves have not been thought to help trigger the disease. Instead,

scientists have believed these antibodies are produced after a person's

T cells had begun attacking the pancreatic cells.

But in the new mouse study, Dr. Ali Naji of the University of

Pennsylvania in Philadelphia and his colleagues found that antibodies

passed from mother to offspring were key in the odds that the offspring

would develop a type 1 diabetes-like condition.

In two of their experiments, the researchers used female mice that had a

diabetes-like disease but were unable to produce antibodies against

insulin. The offspring of these animals showed reduced rates of the

disease. Similar protective effects occurred when the researchers

implanted mouse embryos that were genetically susceptible to the disease

into surrogate mothers not prone to diabetes.

According to the researchers, these findings suggest maternal antibodies

could play an important role in activating an abnormal T cell response

in people who are susceptible to type 1 diabetes. They add that more

research is needed to see if antibody transmission from non-diabetic

mothers might affect diabetes development in children who are

genetically susceptible.

If all of this is borne out, von Herrath explained, it might be possible

to prevent some cases of early childhood type 1 diabetes by eliminating

these maternal antibodies.

However, he pointed out, maternal antibodies are naturally cleared from

an infant's blood by about age 9 months. " It is reasonable to assume, "

von Herrath said, " that (the antibodies) are very unlikely to play a

role in triggering disease in older individuals. "

Besides genetic susceptibility, the researcher noted, still-unproven

environmental factors--possibly certain viruses--are believed to

contribute to the onset of type 1 diabetes. It may turn out, according

to von Herrath, that maternal antibodies play an important role in

triggering diabetes earlier in childhood, while environmental factors

take on greater importance in later-onset cases.

SOURCE: Nature Medicine 2002;8:331-333, 399-402.