Identification of autoantibodies against HIF1a in patients with anorexia nervosa and their potential role in hepatic cytolysis.

Anorexia nervosa (AN) is a severe, potentially life-threatening psychiatric disorder characterized by an intense fear of weight gain, a distorted body perception and an extern food restriction leading to an abnormally low body weight. In AN patients, malnutrition is often associated with hepatic cytolysis. A growing body of evidence support an association between AN and auto-immunity. In this exploratory study, we revealed for the first-time the presence of autoantibodies targeting hypoxia-inducible factor 1 alpha (HIF1a) in AN. We evidenced the presence of autoantibodies against HIF1a in 22% of AN patients, which were absent in patients with other metabolic disease as type-I diabetes or in healthy subjects. In addition, we found that HIF1a autoantibodies was associated with hepatic cytolysis in 80% of AN patients and that their levels significantly correlated with those of ALT (alanine aminotransferase). In-vitro experiments demonstrated that HIF1a autoantibodies induced hepatocyte lysis, suggesting a potential link between these autoantibodies and liver dysfunction in AN patients. Altogether, our data reveal an implication of HIF1a autoantibodies in AN with hepatic cytolysis. Future investigation will explore their potential as a diagnostic or a prognostic marker in AN, but also other diseases since dysregulated hypoxia pathway has been implicated in other pathologic conditions.