Previously, we identified that a majority of patients with anorexia nervosa (AN) and bulimia nervosa (BN) as well as some control subjects display autoantibodies (autoAbs) reacting with ␣-melanocyte-stimulating hormone (␣-MSH) or adrenocorticotropic hormone, melanocortin peptides involved in appetite control and the stress response. In this work, we studied the relevance of such autoAbs to AN and BN. In addition to previously identified neuropeptide autoAbs, the current study revealed the presence of autoAbs reacting with oxytocin (OT) or vasopressin (VP) in both patients and controls. Analysis of serum levels of identified autoAbs showed an increase of IgM autoAbs against ␣-MSH, OT, and VP as well as of IgG autoAbs against VP in AN patients when compared with BN patients and controls. Further, we investigated whether levels of these autoAbs correlated with psychological traits characteristic for eating disorders. We found significantly altered correlations between ␣-MSH autoAb levels and the total Eating Disorder Inventory-2 score, as well as most of its subscale dimensions in AN and BN patients vs. controls. Remarkably, these correlations were opposite in AN vs. BN patients. In contrast, levels of autoAbs reacting with adrenocorticotropic hormone, OT, or VP had only few altered correlations with the Eating Disorder Inventory-2 subscale dimensions in AN and BN patients. Thus, our data reveal that core psychobehavioral abnormalities characteristic for eating disorders correlate with the levels of autoAbs against ␣-MSH, suggesting that AN and BN may be associated with autoAb-mediated dysfunctions of primarily the melanocortin system.anorexia ͉ autoimmunity ͉ behavior ͉ bulimia ͉ hypothalamus N europeptides are important transmitters in the brain limbic and neuroendocrine systems involved in the regulation of different modalities of feeding, social and defensive behaviors, the stress response, and homeostasis (1). These roles of neuropeptides suggest a possible implication in some neuropsychiatric conditions primarily manifested by behavioral abnormalities (2, 3), including anorexia nervosa (AN) and bulimia nervosa (BN) (4). Although changes in concentrations of some neuropeptides in plasma or in cerebrospinal fluid have been noted in patients with eating disorders (5, 6), the mechanisms underlying these changes are unknown, and the modern therapy of eating disorders adopts the symptomatic approach (7).In search of possible peptidergic mechanisms underlying eating disorders, we recently found that a majority of a group of Swedish AN and BN patients display autoAbs against ␣-melanocyte-stimulating hormone (␣-MSH) (8), a melanocortin peptide involved in appetite control (9-12). AutoAbs against adrenocorticotropic hormone (ACTH) and luteinizing hormone-releasing hormone (LHRH) also were identified in some patients and controls (8). The growing evidence of the immune system's critical involvement in some neurological and psychiatric disorders (13) suggests that autoAbs reacting with neuropeptides responsible for the c...

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