Study Reveals a Possible Reason Why More Women Than Men Have Lupus

While both men and women can get lupus, it’s well-established that the autoimmune condition is more common among women as research shows only between 4 and 22 percent of those with lupus are male. A new study offers a potential explanation for why the condition favors those with two X chromosomes.

The study, published last week in the journal Science Immunology by a group of scientists from Inserm, the French National Institutes of Health, focused on the expression of toll-like receptor 7 (TLR7), a gene on the X chromosome that is important in inducing antiviral immune responses. Usually, for people with two X chromosomes, a process called X chromosome inactivation silences expression of TLR7 on one of the two X chromosomes. Past animal studies have suggested that TLR7, the protein created by the TLR7 gene, deficiency protects mice against lupus, while TLR7 over-expression induces systemic autoimmunity.

Researchers studied blood samples of healthy women as well as men with one Y and two X chromosomes (a condition called Klinefelter syndrome, which has also been shown to increase the risk of having lupus). They found that TLR7 was able to evade X chromosome inactivation in some cells of both the women and XXY men — which means TLR7 was being over-expressed.

Jean-Charles Guery, one of the study’s authors, told The Mighty that though previous animal studies established TLR7 as a risk factor for SLE, it had never been demonstrated on primary human cells. “We uncovered a new mechanism explaining sex-related differences in immunity,” he said.

The discovery that TLR7 can evade inactivation makes the study’s authors think that having two X chromosomes is connected to a greater risk of having lupus. Guery said the evolution of lupus, as well as the response to treatment, is hard to predict, so this research could be helpful in classifying SLE patients based on the expression of TLR7 on both chromosomes.

This study, along with other research, also suggests limiting TLR7 levels could be a potential treatment.

“One can speculate that lupus women presenting a high frequency of TLR7 biallelic cells could have more chance to evolve towards a more severe form of the disease, or to experience disease relapses more often than women with low levels of biallelism,” he said.

Not only is Lupus more prevalent in women, it’s also particularly common — and often more severe — in women of color. Research has suggested that genes associated with more severe lupus are more common among non-white women. However, the differences in diagnosis rates between races even out when income level is factored in.

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