Pregnant women carrying babies with a different genetic makeup in their immune systems may have a greater risk of developing rheumatoid arthritis, according to new research being presented at the American Society of Human Genetics’ annual meeting in San Diego.
The higher risk – which apparently lasts long after the pregnancy ends — could help explain why women are more likely to develop the rheumatoid arthritis (RA) than men.
“During pregnancy, you’ll find a small number of fetal cells circulating around the mother’s body, and it seems that in some women, they persist as long as several decades,” said Giovanna Cruz, a graduate student at the University of California, Berkeley and first author of the new study.
“Women with rheumatoid arthritis are more likely to have this persistence of fetal cells, known as fetal microchimerism, than women without the condition, suggesting that it is a potential risk factor for the development of rheumatoid arthritis.”
Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack the tissues lining the joints, causing painful swelling, inflammation and bone erosion. As the disease progresses, many RA patients become significantly disabled. About 1.5 million Americans and 1% of adults worldwide suffer from RA.
Women are three times more likely to develop RA, with peak rates among women in their 40s and 50s. Some versions of the immune system gene HLA-DRB1, known as the shared epitope alleles, are associated with the condition. HLA genes regulate the immune system’s response to infection and in cases of organ transplantation they can “reject” donated organs.
Cruz believes the female predilection for RA strongly suggests that genetic factors involved in pregnancy may also be involved.
“Why it happens, we don’t know, but we suspect HLA genes and their activity may be involved,” she explained.
Researchers analyzed the genes of women and their children with and without the shared epitope or other forms of HLA genes associated with RA. They found that children with the high-risk alleles – inherited from their fathers – increased their mothers’ risk of rheumatoid arthritis.
A woman’s immune system may detect proteins produced by the fetus and mistakenly tag lingering fetal cells as a threat, causing an immune reaction and symptoms of rheumatoid arthritis.
“We don’t yet understand how the shared epitope and other HLA alleles influence rheumatoid arthritis risk, but one possibility is that interactions between the proteins these genes encode may stimulate the autoimmune symptoms of the disease,” Cruz said.
In addition to explaining why women are at increased risk of rheumatoid arthritis, the findings may lead to new ways of assessing a woman’s risk of disease depending on whether her children or partner carries high-risk versions of HLA genes. Other future research includes genetically analyzing multiple generations of RA cases.