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)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
250
When blood is drawn as part of the treatment, three additional dry tubes will be taken for the immunology laboratory (see study diagram). These three dry tubes will be used to test for 1/ anti-nuclear autoantibodies and those associated with hepatic autoimmune pathologies 2/ AAHIF and assess their pathogenic potential using techniques already developed. The third dry tube will be sent to the Biogénopole Biological Resource Center (CHU Timone, APHM).
In the event of AAHIF positivity, a second sample will be taken between 12 and 16 weeks later to verify the persistence of autoantibodies: Visit 2.
Assistance Publique Hopitaux De Marseille
Marseille, France
Determination of anti-HIF1a autoantibodies (AAHIF) in comparison with the presence of hepatic cytolysis in patients with anorexia nervosa and undernutrition
Comparison of the prevalence of anti-HIF1a autoantibodies (AAHIF) in patients with AM according to the presence or absence of hepatic cytolysis.
Time frame: From enrollment to the end of study at 36 months
Rate of AAHIF in a population of healthy subjects
Time frame: From enrollment to the end of the study at 36 months
Rate of AAHIF in patients without anorexia nervosa and with hepatic cytolysis.
Time frame: From enrollment to the end of the study at 36 months
Rate of AAHIF in patients with anorexia nervosa and suffering from malnutrition
Time frame: From enrollment to the end of the study at 36 months
Rate of AAHIF according to clinico-biological criteria for AOS identified in routine care
age, sex, type of AN (pure or mixed restrictive, restrictive and hyperphagic/purgative), duration of disorders, attitudes and behaviors related to AN (assessed by the Eating Disorder Inventory 2 EDI 2 questionnaire), weight, BMI, weight loss in 1 month, weight loss in 6 months or since onset of illness, severity of undernutrition, presence of problematic physical hyperactivity (assessed by the Exercise Dependence Scale-Revised EDSR questionnaire), presence of amenorrhea, use of enteral nutrition, associated treatments, leukocytes, neutrophils, lymphocytes, hemoglobin, platelets, creatinine, urea, AST, ALT, GGT, fasting blood glucose, PT, albumin, pre-albumin (transthyretin), vitamin B12, folate, vitamin D, ferritin.
Time frame: From enrollment to the end of the study at 36 months
Pathogenic potential in vitro of AAHIF in hepatic cytolysis
Functional effects of the purified AAHIF fraction on hepatocyte cell lysis and its impact on HIF1a-dependent signaling.
Time frame: From enrollment to the end of the study at 36 months
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