Tim Radford, science
Monday February 19, 2001
Women could be 10 times more likely than men to suffer from rheumatoid arthritis, lupus, multiple sclerosis and other autoimmune diseases because they carry alien tissues in their bloodstreams - cells from their children and mothers.
Lee Nelson of the University of Washington told the American Association for the Advancement of Science in San Francisco that even 30 years after the birth of a son, male foetal cells could be detected in a woman's blood stream at levels of one in a million.
The presence of these alien cells could indirectly affect the mother's immune system. Immune systems work by detecting and attacking invading cells - bacteria, viruses and so on. Sometimes, immune systems attack their own host, to cause scleroderma, multiple sclerosis and up to 100 other diseases. Autoimmune diseases are among the top 10 killers of women under the age of 65.
"Traditionally, autoimmune diseases are described as your cells attacking your own healthy tissue," she said. "Our findings raise the question as to whether some autoimmune diseases are not entirely autoimmune, whether they actually have a component that is non-self. It's really an entirely new paradigm."
Her research began with rheumatoid arthritis, which goes into remission when women are pregnant but returns after delivery. Immunologists have been interested for decades in why babies aren't rejected after conception, in the way that transplanted organs are rejected by the immune system. But the invasion by a "stranger" turned out to last far longer than nine months.
"In women who have had, for example, a son, you can look 10, 20 or 30 years later at a drop of blood, and find a male cell in there. Similarly you would find cells from a daughter. It's just a little easier to track a male cell in a woman," Dr Nelson said. "The basic theme is that pregnancy is an immunologic event, it is not just a change in hormones, it's actually exposure to a being who is half yours, because half the genes come from the father."
Some of the mother's cells went into the child as well. There were other ways of acquiring a "stranger" within - from a blood transfusion, from a twin, and even from a twin you never knew you had, because many pregnancies began as twins, with one of them lost at a very early stage.
"Probably those cells have a beneficial, neutral or detrimental function depending on what particular relationships there are of the genes that help you determine what is self, what is other," said Dr Nelson. It could explain why women had more autoimmune disease than men, because there were more chances of carrying alien immune system cells.
These were a set of genes on the sixth chromosome, essential to distinguishing self and non-self, called the human leukocyte antigens, or HLA genes. Knowledge of how these genes work could help scientists think of widely different illnesses as stemming from one source. It could also explain why some diseases retreated during pregnancy, and then became better or worse afterwards. It might also explain why one twin might have the disease, but another did not. One child would develop multiple sclerosis, but his or her identical twin had only one chance in 20 of developing the same disease
"It's a fascinating area and it will give us, hopefully, a whole new way of treating these diseases because we can target those cells," she said.
One of the first targets for new kinds of treatment could be scleroderma, which affects about 14 in a million worldwide - mostly mothers. It causes hardening of the skin on the hands and face, and pain in the joints. In some forms it hardens internal tissue, causing organ failure and death.