Study Sheds Light on the Role of X Chromosome Inactivation in Lupus

31st July 2024 – by Aaruthy Suthahar

Researchers at TwinsUK have conducted a study examining the role of the X chromosome in systemic lupus erythematosus (lupus), an autoimmune disease that predominantly affects females. The study, involving nearly 1,000 female participants, found significant differences in X Chromosome Inactivation (XCI) between lupus patients and healthy controls.

Lupus is a condition where the immune system attacks the body’s tissues, leading to inflammation and damage. Despite extensive research, the reasons why 90% of lupus patients are female remain unclear. One theory suggests that the sex chromosomes, particularly the X chromosome, may play a role.

In females, one of the two X chromosomes is randomly inactivated in each cell, a process known as XCI. This study measured changes in XCI in immune cells and discovered that only 7% of lupus patients showed changes in XCI, compared to 30% typically seen in healthy females. Moreover, among those with more severe lupus, only 3% exhibited changes in XCI.

To further validate these findings, researchers studied twin pairs from TwinsUK where one twin had lupus, and the other did not. The results were consistent: twins with lupus had fewer changes in XCI than their healthy counterparts.

Interestingly, these findings differ from previous research on other autoimmune diseases such as thyroid disease and rheumatoid arthritis, indicating distinct mechanisms underlying different autoimmune conditions. Instead of a broad pattern of XCI changes, the study found a correlation between XCI and the “interferon signature,” a marker of lupus disease activity.

These insights suggest that the role of XCI in lupus is unique and may not follow the patterns observed in other autoimmune diseases. More research is needed to understand how these changes in XCI affect immune function and their implications for infection defence, especially as individuals age.

First author Dr. Amy Roberts explained:

“Thanks to the TwinsUK volunteers, we were able to demonstrate differences in X chromosome inactivation between healthy controls and people with lupus. Not only does this research help us understand lupus but also how our immune system changes with age – an area we are actively researching further.”

This study represents a significant step forward in understanding the complex biology of lupus and underscores the importance of examining sex-specific factors in autoimmune diseases.