The role of X-chromosome inactivation in female predisposition to autoimmunity

Abstract

We propose that the phenomenon of X-chromosome inactivation in females may constitute a risk factor for loss of T-cell tolerance; specifically, skewed X-chromosome inactivation in the thymus may lead to inadequate thymic deletion. Using a DNA methylation assay, we have examined the X-chromosome inactivation patterns in peripheral blood from normal females (n=30), and female patients with a variety of autoimmune diseases (n=167). No differences between patients and controls were observed. However, locally skewed X-chromosome inactivation may exist in the thymus, and therefore the underlying hypothesis remains to be disproved.