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

摘要

The hypothalamic arcuate nucleus is involved in the control of energy intake and expenditure and may participate in the patho-genesis of eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Two systems are of particular interest in this respect, synthesizing a-melanocyte-stimulating hormone (a-MSH) and synthesizing neuropeptide Y, respectively. We report here that 42 of 57 (74%) AN and/or BN patients studied had in their plasma Abs that bind to melanotropes and/or corticotropes in the rat pituitary. Among these sera, 8 were found to bind selectively to α-MSH-positive neurons and their hypothalamic and extrahypo-thalamic projections as revealed with immunostaining on rat brain sections. Adsorption of these sera with α-MSH peptide abolished this immunostaining. In the pituitary, the immunostaining was blocked by adsorption with +-MSH or adrenocorticotropic hormone. Additionally, 3 AN/BN 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 AN/BN staining. These data provide evidence that a significant subpopu-lation of AN/BN patients have autoantibodies that bind to a-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 mela-nocortin circuitry/LHRH system and/or in other central and peripheral sites relevant to food intake regulation, to what extent such effects are related to and/or could be involved in the pathophys-iology or clinical presentation of AN/BN, and to what extent increased stress is an important factor for production of these autoantibodies.