UCSF researchers identify a molecular link between thymic tumors and autoimmunity

By Kristen Bole on February 26, 2010

UCSF researchers have identified a molecular mechanism that explains why patients with tumors of the thymus, or thymoma, often develop autoimmune disorders.
 
The team’s findings are published as a case report and letter to the editor in the February 25 issue of the New England Journal of Medicine.
 
The case report involves a 64-year-old patient who displayed clinical signs of what is known as autoimmune polyglandular syndrome type 1 (APS1), a hereditary disease commonly characterized by multiple autoimmune disorders that often target endocrine glands.  These disorders can include type 1 diabetes, thyroiditis, and adrenal gland insufficiency.
 
APS1 is known to be associated with defects in the Autoimmune Regulator (AIRE) gene, which had previously been found to work in the thymus to help T-cells differentiate between “self” and “non-self” in immune responses.  What confounded this patient’s medical team was the fact that she showed the symptoms of APS1, but had no defect in the AIRE gene that is normally associated with APS1.
 
The key to unlocking the case came when the UCSF team discovered that the patient had developed the thymoma during the same time frame that she developed the APS1 symptoms.  The team reasoned that abnormal AIRE function in the thymoma was the underlying cause of the clinical syndrome.  This proved to be correct as examination of the patient’s thymic tumor showed a lack of correct AIRE expression and function.  Thus, an acquired AIRE defect in the tumor provoked the development of APS1.
 
“We have known that patients who develop thymoma often develop autoimmune syndromes, but the mechanism was previously unknown,” said senior author Mark S. Anderson, MD, PhD, of the UCSF Diabetes Center. He explained that the case has implications for treating autoimmunity in patients that develop such thymic tumors and raises the possibility that acquired problems in AIRE expression can provoke autoimmunity in later life.
 
Co-authors on the paper include first author Mickie H. Cheng, MD, PhD; Una Fan and Navdeep Grewal, with the UCSF Diabetes Center; Michael Barnes, MD; Anand Mehta, MD; Steve Taylor, MD, and Elizabeth J. Murphy, MD, PhD, of UCSF; and Eystein S. Husebye, MD, of the University of Bergen, Norway.
 
Link to NEJM paper: http://content.nejm.org/cgi/content/full/362/8/764