Exploring Autoimmune Prevalence and X Chromosome Inactivation in Systemic Lupus Erythematosus

Autoimmune diseases, including systemic lupus erythematosus (SLE), are more common in women than men, and scientists are still trying to figure out why. One reason may be related to the number of X chromosomes a person has. Typically, females have two X chromosomes (XX), and males have one X and one Y (XY). However, some males have an additional X chromosome (XXY), and some females have an extra X too (XXX). The additional X chromosome in females might play a role in the predisposition to autoimmune diseases like Sjogren’s syndrome and lupus. A recent study examines how inactivation of the X chromosome might be connected to SLE. 

In the study, researchers examined blood samples from 181 people with SLE to determine which X chromosome was inactivated. Normally, one X chromosome is inactive in every cell, but in people with lupus, there was less inactivation or “skewing” compared to healthy people. Additionally, skewing was more pronounced if renal disease was involved. Researchers also found that people living with lupus under the age of 40 were less likely to have skewed X chromosome inactivation, which typically increases with age in women. The study concluded that X chromosome inactivation is a result of SLE and not the cause of the disease. This finding challenges earlier research that suggested X chromosome inactivation might be responsible for the higher rates of autoimmune disease in women. 

Researchers suggest that future studies need to explore multiple factors that may contribute to why women and men are more prone to autoimmune diseases, beyond X chromosome inactivity only; and should consider that there may be multiple pathways and several mechanisms that are potentially involved. Learn more about what causes lupus.

Read the study