Autoimmune Disease

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Original article:

http://my.webmd.com/content/article/1728.72837

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Autoimmune Disease: It's Not Just the Genes

Fetal Cells Spur Immune Response Years Later

By Dan Ferber, PhD

WebMD Medical News

Reviewed by Dr. D. Vogin

Feb. 20, 2001 (San Francisco) -- Children with hereditary diseases have

their parents to blame, according to the conventional wisdom of geneticists.

But in an ironic twist of fate, a mother can contract an autoimmune disease

by reacting to the fetal cells from her child that remain in her body for

years or even decades after the child is born, according to results

presented here Saturday at the annual meeting of the American Association

for the Advancement of Science.

The results could help explain why 75% of all patients with autoimmune

diseases are women.

The more than 80 autoimmune disorders, including rheumatoid arthritis,

lupus, and multiple sclerosis, occur when the body attacks and destroys its

own tissue -- joint tissue in the case of rheumatoid arthritis, blood

vessels and connective tissue in the case of lupus, or the insulating

coating of the nerves in the case of multiple sclerosis. Grouped together,

autoimmune diseases are among the top 10 leading causes of death for women

under 65.

" It is not a minor medical and public health problem, " says Noel Rose, MD,

PhD, director of the Autoimmune Disease Research Center at s Hopkins

University in Baltimore.

Although autoimmune disorders run in families and susceptibility genes

have been identified, identical twins of patients usually don't get the

disease. That means that there must be an environmental trigger to set off

the autoimmune response, Rose says.

But there's more to autoimmune disease than genes and environmental

triggers, says J. Lee , MD. Rather than reacting to the body's own

cells, she suspects the immune system could be reacting to cells from a

long-grown child that the mother once carried. is an associate member

of the Fred Hutchinson Research Center and an associate professor of

rheumatology at the University of Washington in Seattle.

's suspicions were roused in 1995, when other researchers found that

fetal cells survived in the mother's tissues for years. The mother can form

antibodies to such cells.

" Pregnancy ... is exposure to a body that's half foreign, " she says.

examined middle-aged women who had sons. Half of them had a

potentially fatal autoimmune disease called scleroderma that can cause

connective tissue to harden, sometimes causing organ failure and death. The

researchers found that the scleroderma patients had eight times more male

cells in their blood -- years after they'd given birth -- than did the

mothers without the disease.

The results could also explain how men and women without children get

scleroderma, she says. Babies in the womb pick up some of their mother's

cells, so foreign " maternal cells could also engraft and persist in a

child, " she says.

Scleroderma occurs in 14 of every million people, and is much more common

in women than in men.

Other findings in mice show that it takes more than the wrong gene to

cause autoimmune disease.

A team led by Faustman, MD, PhD, studied a genetically identical

line of mice that usually develop type 1 diabetes. But rather than develop

diabetes, some of the mice developed rheumatoid arthritis instead. Just as

in humans, the arthritis occurred about 75% of the time in females, and it

occurred in middle age. Faustman is director of the Immunobiology Labs at

Massachusetts General Hospital and an associate professor of medicine at

Harvard Medical School in Boston.

" It demonstrates the same gene can cause two different phenomena, " she

says. What's more, the mice also come down with the same symptoms of

rheumatoid arthritis as humans, and middle-aged females tend to get it more

than anybody else. That makes this mouse line a great model for researchers

to study the causes and possible treatments of rheumatoid arthritis,

Faustman says.

The results of both studies could help researchers find " novel ways of

approaching treatment and even possible prevention of autoimmune disease, "

Rose says. Today, the best physicians can do is to treat patients with drug

that dampens the immune response, but in the future drugs that target

foreign cells could help.

What's more, the fact that both men and women have cells from our mothers,

and women also have cells from their children, could even alter our

traditional notion of who we are, says.

" Our concept of self will have to be conditional, " she says -- it seems

we're not necessarily the people we thought we were.

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