VICTORIA — Janine Pigeon has had rheumatoid arthritis for half her life and was happy to act as a research subject in a study of the disease. But she said she was stunned to learn she may have inherited it from a son.
“They know it’s one of my boys but they just won’t tell me which one. So I can’t go and say ‘You little dickens, you,’” the 77-year-old mother of five said at her Victoria apartment.
Pigeon was one of 13 women from Vancouver Island and their families who agreed to become subjects to examine a phenomenon in which cells travel in both directions across the placenta. A mother’s cells will take up residence in a developing child, while cells from the child will take up residence in the mother.
This residence can last for decades, even lifetimes and is known as “microchimerism.”
The prefix “micro” denotes the small, cellular level. “Chimera” denotes an organism containing a mixture of genetic material, after the Greek mythical creature with a lion’s head, a goat’s body and a snake’s tail.
Microchimerism is being linked to a number of auto-immune diseases, disorders in which a body’s protective mechanisms fights themselves — such as rheumatoid arthritis.
In the research, doctors dissected one of the characteristic nodules formed by rheumatoid arthritis from Pigeon’s knuckle. When the nodule was tested at the Fred Hutchinson Cancer Research Center in Seattle, male DNA was found at its centre. It was traced to one of Pigeon’s sons.
This suggests foreign genetic material may have triggered the immune response that triggered the disease.
The results of the research project have been presented at two international science symposiums, in Kobe, Japan, and Atlanta, Georgia.
Rheumatoid arthritis is chronic and incurable. It affects many tissues, but principally attacks the joints, especially the fingers, wrists, shoulders, knees and hips. As the tissue in the joint breaks down, it can lead to deformity and severe physical handicaps.
It attacks three times more women than men and is characterized by the formation of nodules under the skin, near affected joints.
“What I didn’t realize until I got involved with this project is that my practice is invaluable to the research community because of the relationships, the social credit built up over years,” said rheumatologist Dr. Christopher (Chipps) Atkins, the lead Victoria researcher.
Research people ask “How did you get all this? How did you manage to do all this?” he said.
“It’s because (we) have gone into peoples’ houses and we know these people and built up these relationships.”
The Victoria research succeeded because it joined forces with a bigger project at the grant-supported Fred Hutchinson centre.
Atkins’s interest was sparked by a February 2008 article in Scientific American. He contacted the writer, Dr. J. Lee Nelson, of the Fred Hutchinson, a professor of medicine at the University of Washington in Seattle. Atkins suggested the idea of investigating rheumatoid arthritis nodules for foreign cells.
Nelson, who also specialized in rheumatology, suggested the researchers concentrate on looking for cells of sons in female patients.
That’s not to suggest cells from a developing baby girl couldn’t be passed to a mother. But the presence of the single Y chromosome on a male cell can make it much easier to find in the vast ocean of XX chromosome cells in a woman’s body.
The next step for Atkins was to recruit a team of researchers in Victoria, all of whom had to be willing to undertake the work for no money.
Dr. David Naysmith, a plastic surgeon, agreed to perform surgeries to remove the nodules. Pathologist Dr. Nick van der Westhuizen, a pathologist and an associate with the University of British Columbia, agreed to receive the nodules and prepare the tissue for analysis.
Atkins also recruited Janet Woo, a former researcher with the BC Cancer Agency, now living in Victoria, with whom he had worked in the past.
Woo’s assistance proved crucial in forming the hypothesis suggesting proteins on the surface of foreign invader cells may, somehow, trigger the auto-immune response leading to rheumatoid arthritis.
Atkins and his colleagues worked for free but the genetic analysis performed at the Fred Hutchinson ran into tens of thousands of dollars.
It was the hypothesis, supported by solid data, that made for ultimate scientific publishing success, Atkins said.
Meanwhile, Nelson’s study of microchimerism continues. She said it should be noted that microchimerism may have a beneficial effect as well as causing disease.
For example, statistics show women who have had children are less likely to develop breast cancer.
“Like many things in biology they may have a good function and also the potential, in certain circumstances, for being a problem,” Nelson said.
The research will now likely concentrate on what kind of cells become long-lived foreign immigrants and how they react with the host’s immune system. “That might lead us to a tool that we could use therapeutically,” Nelson said.