Autoantibodies against neuropeptides are associated with psychological traits in eating disorders

Abstract

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...

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

“…Approximately 74% of human sera bound to rat pituitary melanotropes and corticotropes, and approximately 20% selectively bound to α-MSH projections. When adsorbed with α-MSH and ACTH peptides, reduced staining was observed for both peptides, demonstrating that plasma auto-Abs from ED individuals and administered peptides share similar binding sites and can cross-react (Fetissov et al, 2002(Fetissov et al, , 2005.…”

“…Auto-Abs against the peptides of interest showed correlations with EDI-2 scores in the ED groups; α-MSH demonstrated the highest correlation. Furthermore, auto-Abs against adrenocorticotropic hormone (ACTH) correlated positively (in AN) and negatively (in BN patients) with maturity fears, a wish for the security of pre-adolescent years in response to the demands of adulthood (Fetissov et al, 2005). A translational component of this study is discussed below.…”

“…This study suggests that at least a part of sex-differences in food intake, immune response, kinetics and energy balance are related to differences in the prevalence of E. coli K12 in male and female rats, which contributes to differences in satiety, feeding, and emotional behavior in rats (Tennoune et al, 2015). Fetissov et al (2005) investigated correlations of auto-Ab levels [against α-MSH, adrenocorticotropic hormone (ACTH), oxytocin (OT) and arginine vasopressin (AVP)] with ED-related psychological traits in both control and ED participants. Although auto-Abs were found in both groups, suggesting possible homeostatic functions, their levels differed.…”

“…The gut microbiota is not necessary for the production of auto-Abs, but can modulate their levels and may serve as a potential target for ED interventions (Fetissov et al, 2008a). Auto-abs against central, appetite-regulating peptides like α-MSH alter melanocortin system functioning, which can contribute to non-metabolic alterations in eating behavior and food craving, and may explain the clinical correlations between auto-Abs and self-reported ED symptoms (Fetissov et al, 2005;Tennoune et al, 2014;Kleiman et al, 2015b). Though the presence of auto-Abs is insufficient to cause EDs (Fetissov et al, 2005), high blood-brain-barrier permeability, which can result from stress, may be involved in triggering pathogenesis.…”

“…Auto-abs against central, appetite-regulating peptides like α-MSH alter melanocortin system functioning, which can contribute to non-metabolic alterations in eating behavior and food craving, and may explain the clinical correlations between auto-Abs and self-reported ED symptoms (Fetissov et al, 2005;Tennoune et al, 2014;Kleiman et al, 2015b). Though the presence of auto-Abs is insufficient to cause EDs (Fetissov et al, 2005), high blood-brain-barrier permeability, which can result from stress, may be involved in triggering pathogenesis. The research presented identifies auto-Abs against key peptides as not only treatment targets, but also as markers for the function of the gut-brain axis and for response to microbiota-related ED treatments (Inui et al, 2015) and as potential means of identifying ED risk factors (Tennoune et al, 2015).…”