Identification of Anti-HIF 1alpha Autoantibodies in Patients With Anorexia Nervosa and Characterization of Their Pathogenic Potential in Undernutrition-associated Hepatic Cytolysis

Plain-language summary

Anorexia nervosa (AN) is a psychiatric disorder belonging to the eating disorders (EDs). It is internationally recognized as a priority for improving health care. Among the markers of severity of undernutrition is hepatic cytolysis. Around 30-50% of patients with AN present with hepatic cytolysis, of variable intensity, and usually associated with severe undernutrition. In a previous study, we demonstrated the presence of autoantibodies against HIF1alpha (Hypoxic inducible Factor 1 alpha) in 22% of cases in a sample of patients with AN. HIF1alpha (HIF1a) is a major transcription factor involved in the regulation of satiety and hunger. These autoantibodies were positive in 80% of AN patients with hepatic cytolysis. Taken together, these data led us to hypothesize an anti-HIF1a autoimmune mechanism in AN, potentially involved in the patients' hepatic cytolysis. This pioneering study, demonstrating the existence of anti-HIF1a autoantibodies, was carried out on a population of 18 patients with AN. To extend investigator's hypothesis, these results need to be confirmed on a larger number of patients, thus increasing the number of patients with AN and hepatic cytolysis. To determine the relevance of these autoantibodies in AN, "healthy" subjects and patients without AN but with hepatic cytolysis should be tested in parallel. Finally, the in vitro pathogenic potential of autoantibodies can be confirmed on a larger scale and studied in greater detail. The main aim of our study is to evaluate the association between the presence of anti-HIF1a autoantibodies (AAHIF) and that of hepatic cytolysis in patients with anorexia nervosa and undernutrition. This study is a prospective, cross-sectional, descriptive, multicenter, 2-arm study. 250 patients will be included. Experimental group (n=100) * Patients with anorexia nervosa and undernutrition with hepatic cytolysis (CH) (n=70) * Patients with anorexia nervosa and undernutrition without hepatic cytolysis (n=30) Comparator control groups (n=150) * Control patients under 18 years of age, treated at the CHU de la Timone for scheduled non-inflammatory surgery (orthopedic, ENT, etc.) (n=50): Minor patients * Patients (children and adults) with hepatic cytolysis without anorexia nervosa (n=50): Patients without AN with CH * Samples from French blood donation establishment: control group consisting of biological blood samples from healthy individuals from the Etablissement Français du Sang (n=50)

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