Ghrelin reactive autoantibodies in restrictive anorexia nervosa

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 27; no. 4; pp. 407 - 413
• Main Authors: Terashi, Mutsumi, M.Sc, Asakawa, Akihiro, M.D., Ph.D, Harada, Toshiro, M.D., Ph.D, Ushikai, Miharu, M.Sc, Coquerel, Quentin, M.Sc, Sinno, Maria Hamze, Ph.D, Déchelotte, Pierre, M.D., Ph.D, Inui, Akio, M.D., Ph.D, Fetissov, Sergueï O., M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2011; Elsevier; Elsevier Limited
• Subjects: Adult; Anorexia; Anorexia Nervosa - immunology; Antigen-Antibody Complex - blood; Appetite; Autoantibodies - blood; Autoimmunity; Biological and medical sciences; Body Mass Index; Eating disorders; Enzyme-Linked Immunosorbent Assay; Feeding. Feeding behavior; Female; Food; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Ghrelin - blood; Ghrelin - immunology; Humans; Insulin resistance; Malnutrition; Peptide hormones; Peptides; Rodents; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Weight control; Young Adult; Japan; Appetite; Autoimmunity; Malnutrition; Peptide hormones; Eating disorders; Nutrition disorder; Peptide hormone; Autoantibody; Anorexia nervosa; Eating disorder; Vertebrata; Mammalia; Ghrelin
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2011.01.002

Abstract Objective Subjects with restrictive anorexia nervosa (AN) display increased basal plasma levels of ghrelin that normalize after refeeding. The mechanism responsible for increased ghrelin levels in AN is unknown. We studied if changes of ghrelin reactive autoantibodies (autoAbs) could explain elevated plasma ghrelin in AN. Methods Plasma levels of autoAbs reactive with ghrelin and des-acyl ghrelin were measured by enzyme-linked immunosorbent assay in subjects with AN before and 1 mo after hospitalization (refeeding) and compared with healthy controls and with plasma levels of ghrelin peptides. Results Decreased levels of immunoglobulin (Ig) G, IgM, and IgA classes of autoAbs reacting with acyl ghrelin were found in patients with AN. Addition of des-acyl ghrelin but not of acyl ghrelin peptides at 10−8 M to plasma before enzyme-linked immunosorbent assay showed in patients with AN but not in controls high levels of IgG autoAbs reacting with des-acyl ghrelin as a result of dissociation of des-acyl ghrelin autoAbs in immune complexes. Plasma levels of acyl and des-acyl ghrelin peptides correlated negatively with des-acyl ghrelin IgG autoAbs. Body mass index, which improved after refeeding, correlated with an increase of acyl ghrelin IgM autoAbs. Conclusion These results show that in patients with AN, ghrelin IgG autoAbs exist mainly as immune complexes with des-acyl ghrelin accompanied by a decrease of a free fraction of these autoAbs binding acylated and des-acyl ghrelin. This decrease of bioavailable ghrelin autoAbs may underlie a long-term elevation of plasma ghrelin levels and the resulting phenomenon of ghrelin resistance in malnourished patients with AN.