Harmful Brain Antibodies Linked to Eating Disorders

Some cases of anorexia and bulimia may be related to an autoimmune disorder involving specific brain structures responsible for feeding behavior. As a result, eating disorders could belong in the same category with other autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

These findings, from a European team headed by Serguei Fetissov, M.D., a senior researcher at Sweden’s Karolinska Institute in Stockholm, were published in the December 9 edition of the Proceedings of the National Academy of Sciences.

Growing evidence, the report said, indicates that anorexia—which is manifested by a primary aversion to food that often results in life-threatening weight loss and ensuing multiorgan failure if untreated—and bulimia—marked by a cyclic binging and purging of food intake with no appreciable weight loss—may have a primary neurobiological origin. While the causes of the disorders remain unclear, some evidence indicates that certain neuropeptides are implicated, including evidence for a role of specific neurons in the hypothalamus associated with energy deprivation or energy excess, which might control food intake and body weight.

The Swedish researchers hypothesized that the hypothalamic systems responsible for the intake of food could be damaged by targeted antibodies in patients with anorexia or bulimia, as has been recently shown for other neurological diseases, most notably, multiple sclerosis. Prior research has implicated specific types of neurons in the hypothalamus that produce two specific peptides thought to be involved in hypothalamic regulation of feeding behaviors: melanotropes, which produce alpha-melanocyte stimulating hormone (α-MSH), and corticotropes, which produce neuropeptide Y.

The group collected blood serum from 57 women patients, aged 17 to 42, diagnosed with either anorexia or bulimia according to DSM-III criteria. Twenty-eight patients had anorexia, 22 had bulimia, and seven had a combination of both. Serum from 13 healthy women volunteers served as a control sample.

Each sample of serum was tested for the presence of antibodies to either melanotropes or corticotropes from rat brain preparations.

Fetissov’s team discovered that nearly 75 percent (42 of the 57 patients) of patients’ serum samples were positive for antibodies that bound to either melanotropes or corticotropes in rat brain pituitary preparations. Probing further, they found that about 20 percent (eight of the 42) had specific antibodies to hypothalamic α-MSH producing neurons. They also found that the binding of those antibodies to the α-MSH producing neurons could readily be reversed by adding α-MSH to the hypothalamic preparations or adding either α-MSH or adreno-corticotropic hormone (ACTH) to the pituitary preparations.

According to Fetissov and his colleagues, the results clearly indicated that “a significant subset of anorexia/bulimia sera contain α-MSH and/or ACTH autoantibodies. Because α-MSH represents the first 13 amino acids of ACTH, it is not surprising that autoantibodies may recognize both or preferentially one of the two peptides.”

They concluded that “because the melanocortin system seems to play an important role in the regulation of food intake and body weight, our data raise the possibility that the disturbance in food intake observed in [anorexia/bulimia] could involve an autoimmune process against α-MSH/ACTH in a subpopulation of patients.”

What Fetissov and his group do not know is how the presence of the antibodies may interfere with neuronal functioning and signaling in human brains, although they offer several possibilities. They also do not know what might cause the production of the antibodies, although two women in the control group also had antibodies present in their serum samples. This suggests, they wrote, “that the presence of α-MSH/ACTH autoantibodies does not necessarily imply the presence of [anorexia or bulimia],” suggesting an interaction between physiology and environment.

An abstract of “Autoantibodies Against Alpha-MSH, ACTH, and LHRH in Anorexia and Bulimia Nervosa Patients” is posted on the Web at www.pnas.org/cgi/content/abstract/222658699v1?. ▪

PNAS 2002 99 17155