Targeting the Inactive X for Correcting Dosage Imbalances in Lupus
Women have two X chromosomes, but men only carry one. In women’s cells, one of the X chromosomes typically switches off most of its genes. We hypothesize that many of these genes turn back on in lupus. Because a large number of genes that control the immune system are on the X chromosome, switching them back on could cause the immune system to function abnormally. To test our hypothesis, we will measure whether silenced genes on the X chromosome have turned back on in cells from patients with lupus. We will then measure the effect of this reactivation on the immune system in mice and determine whether we can reverse it in cells from women with lupus.
The study and what it means for patients:
“Women are much more likely to develop lupus than are men, and the difference may be partly due to their chromosomes. Most genes on one chromosome in women normally shut down. We will test the hypothesis that some of these genes switch back on in lupus, disrupting the immune system. The work could reveal new targets for lupus therapies.”