Pregnant mother’s immune system could yield treatments

In the nine months of pregnancy, mothers-to-be watch for every
sign of life. Oddly enough, to avoid miscarriage, her fetus must
hide from her immune system.

By Carol Flaherty MSU News Service

That is the essence of an article by Montana State University
researcher Ed Schmidt that was featured in a recent issue of
"Cell," a leading cell biology journal.

Schmidt believes that this surprising insight into how the immune
system works in pregnancy could eventually lead not just to fewer
miscarriages but also to solutions for other problems, such as the
rejection of donated organs. His work is funded by the March of
Dimes, which works to prevent birth defects and infant mortality.

The significance of his work comes partially from the
pervasiveness of the gene he worked with in mice. It is so basic to
life that he describes it as "required by all cells, in almost all living
things, at all times."

However, there also are diverse genetic segments attached to the
universal part of the gene.

"I wondered what the diverse material did," Schmidt said.

To see how the gene worked, his research team removed a part of
it from a line of mice.

"We found that in addition to the gene’s requirement for basic
functions, there is an additional bit needed to maintain
pregnancy," he said. "This bit allows the fetus to hide. Without it,
mothers’ immune systems see the fetuses as foreign tissue, as if it
were an invading virus, so mutant fetuses were aborted."

Later, Schmidt eliminated the mothers’ immune systems, and they
gave birth to healthy mice that otherwise couldn’t have hidden as
fetuses.

In some cases, a mother’s immune system may detect a problem
with the pregnancy and thus reject it. However, in other cases,
Schmidt believes a mother’s immune system may be "set too high,"
which could trigger a miscarriage of what would otherwise become
healthy offspring.

The immune systems of mice and humans are virtually identical, so
"these mice should be useful to investigators interested in
improving the outcomes of pregnancies for humans," said Schmidt.

Miscarriages occur in 15 percent of recognized pregnancies,
according to the March of Dimes. However, many miscarriages
occur before a woman even knows she is pregnant. That means
that up to 50 percent of all pregnancies may end in miscarriage.
With each miscarriage, the odds of additional miscarriages
increase.

"The only reason pregnancy works at all is the same reason
five-year-old children get away with so much," Schmidt said.
"They know how to hide. In this case, the placenta hides the
fetus. When it fails to hide the pregnancy from the mother’s
immune system, a miscarriage often occurs.

"In mice, we have seen that some fetuses are predisposed to
rejection, but we know that if we get them over one critical
checkpoint, they will develop into normal healthy mice. So the
question is, what can we do with women whose immune system is
set too high? Can we alter her environment, or prenatal care? Can
we make a very minor and temporary change in the immune
system and change it back after the infant is born? There’s a lot
we still must learn."

He sees other important implications for the findings.

"Since all cells in the body have the same genes, imagine if we
could figure out how to turn on the genes for the placenta’s hiding
system in a kidney’s cells before it is transplanted into a person?"
Schmidt said.

In order to prevent a donor kidney from being rejected, the
recipient’s immune system must be suppressed, opening the
recipient to all sorts of illness.

Perhaps someday, as research along these lines progresses, it may
be possible for transplant recipients to keep both the transplanted
organ and their immune system.

http://newspapers.mywebpal.com/partners/311/public/news344135.html