Why Do Women Face Higher Rheumatoid Arthritis Risk Than Men?

Researchers investigate link between a child’s genetic makeup and RA risk for mothers.

Women may face a higher risk of developing rheumatoid arthritis (RA) than men based on the genetic makeup of their children, according to the results of a recent study.

The development of the painful inflammatory condition has been linked to genetic and environmental factors that include lifestyle and prior infections, with women 3 times more likely than men to develop the disease. Researchers from the University of California at Berkeley found that the higher prevalence of RA in women may be a result of factors involved in pregnancy.

"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,” Giovanna Cruz, MS, first author on the study, said in a press release. “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. Why it happens, we don't know, but we suspect HLA genes and their activity may be involved.”

Some versions of the immune system gene HLA-DRB1 have been found to be associated with RA, as they are known for involvement in the response to infection and for differentiating between cells following an organ transplant. The researchers analyzed female genes with and without certain forms of HLA genes that are associated with the risk of rheumatoid arthritis, and the genes of their children.

The study found that children with high-risk alleles that are inherited from the father raise the mother’s risk of developing RA. As a result, independently of the genetic risk women have of developing RA, an added risk is conferred by carrying and bearing children that carry certain high-risk alleles.

The findings of the study may result in new ways to assess a woman's risk of developing RA dependent on whether her children or partner carry high-risk versions of the genes. As a result, future research will examine multiple generations of RA cases and the role HLA-encoded proteins and microchimerism play in the development of RA.

"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 other words, 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.”