Autoimmune woes target women
Chronicle Medical Writer
Sunday, February 18, 2001
The mystery of why women are three times more likely to suffer autoimmune diseases such as lupus, multiple sclerosis and rheumatoid arthritis may wind up as a tale with many villains.
Hormones, genes, faulty cell mechanisms -- even a woman's own offspring -- are likely culprits in a conspiracy that sets the immune system on a misguided attack on the body's own tissues, scientists said at a conference yesterday.
Autoimmune diseases comprise as many as 80 separate disorders. Taken together, they affect one in five Americans and are among the top 10 leading causes of death for women under 65.
"This is a major public health problem," said Dr. Noel Rose, a pathologist and immunologist at Johns Hopkins University, who was among those speaking on autoimmune diseases at the American Association for the Advancement of Science meeting at the Hilton San Francisco.
Autoimmune diseases have only recently been viewed as a distinct condition - - much like cancer -- in which the same mechanisms are at work, even though they may affect different parts of the body in different patients.
And with statistics showing that autoimmunity is the fourth leading cause of disability among women, women's health advocates are focusing more of their attention on it.
"It's such a striking phenomenon, you'd think we'd know why it occurs more in women," Rose said. "But we don't."
Still, research in the field is picking up. One of the most intriguing new ideas is that the exchange of cells between a mother and her growing fetus may set up conditions that lead the immune system to go off course. Those foreign cells persist in small numbers in both the mother and her child decades after birth.
Dr. J. Lee Nelson, of the Fred Hutchinson Cancer Research Center in Seattle,
found that women with the autoimmune disease scleroderma have 10 times more fetal cells circulating in their blood years after pregnancy than do mothers without the disease.
Even more startling, Nelson said, is the apparent interaction between cells a woman has from her own mother and those she retained from her children.
If the genes that control the immune system match up in a specific way between grandmother and grandchild, the woman carrying cell types from both generations is 19 times more likely to come down with scleroderma, Nelson said.
"It's a fascinating concept -- that you could have a war of generations and you can see its effects in your body," she said.
Heredity is known to play a role in autoimmune diseases, but it is now clear that just because someone has a specific type of gene doesn't mean they are destined to come down with the disease, scientists said.
Instead, those genes set up conditions under which other environmental factors -- everything from the atmosphere in the womb to future infections -- can trigger a self-destructive immune response.
Dr. Denise Faustman of Harvard Medical School said there is new evidence that a defect in the machinery inside the cell creates problems in the assembly of proteins. That, in turn, is linked to the development of Type 1 diabetes, in which the immune system destroys the body's insulin-producing cells.
The defect isn't related to a specific type of gene, but instead to the way the genes are turned on after birth, she said. Studies in mice have shown that the defect appears to be sex-linked, Faustman said. There are now blood tests that detect it and can predict the eventual onset of the disease.
One of the earliest lines of research into the sex differences in autoimmune disease has involved the role of hormones. More than 60 years ago, doctors recognized that women with rheumatoid arthritis usually went into remission when they were pregnant.
Attempts to cure or treat autoimmune disease by giving women male hormones have so far offered limited results.
But a University of Missouri doctor reported yesterday that she has had modest success with a drug that blocks the effect of prolactin, a female hormone important for breast-feeding. About 20 percent of lupus patients have higher-than-normal levels of the hormone.
Meanwhile, the study of autoimmune diseases as a distinct field is beginning to take shape.
Traditionally, the various illnesses have been investigated by the specialists who treat them, with neurologists focusing on multiple sclerosis, endocrinologists on Type 1 diabetes and gastroenterologists on Crohn's disease.
But 10 years ago, the American Autoimmune Related Disease Association was founded, and in 1995 it succeeded in getting the National Institutes of Health's Office on Research on Women's Health to recognize it as a major women's health issue.
In 1999, the NIH spent $30 million on basic research in autoimmune diseases.
And last year, a permanent committee to coordinate research among the many NIH institutes was signed into law.
As treatments come on line that have direct effects on the immune system, Rose said he expects specialists to emerge, just as there are now oncologists who deal with the many forms of cancer.
There are as many as 80 autoimmune diseases. Here are a few:
©2001 San Francisco Chronicle