Autoantibodies against alpha -MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients.

Abstract

The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the pathogenesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing alpha-melanocyte-stimulating hormone (alpha-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN andor BN patients studied had in their plasma Abs that bind to melanotropes andor corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to alpha-MSH-positive neurons and their hypothalamic and extrahypothalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with alpha-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with alpha-MSH or adrenocorticotropic hormone. Additionally, 3 ANBN sera bound to luteinizing hormone-releasing hormone (LHRH)-positive terminals in the rat median eminence, but only 2 of them were adsorbed with LHRH. In the control subjects, 2 of 13 sera (16%) displayed similar to ANBN staining. These data provide evidence that a significant subpopulation of ANBN patients have autoantibodies that bind to alpha-MSH or adrenocorticotropic hormone, a finding pointing also to involvement of the stress axis. It remains to be established whether these Abs interfere with normal signal transduction in the brain melanocortin circuitryLHRH system andor in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to andor could be involved in the pathophysiology or clinical presentation of ANBN, and to what extent increased stress is an important factor for production of these autoantibodies.