Neuropeptide Binding Autoantibodies Regulating Neuroendocrine Communications

Abstract

Immunoglobulin (Ig) molecules or antibodies binding neuropeptides or peptide hormones that regulate motivated behavior, stress, and emotion, such as α-MSH, ACTH, oxytocin, or ghrelin, are naturally present in humans and in rodents in both healthy and disease conditions. The functional role of such autoantibodies was analyzed, showing their constitutive participation as modulators of peptidergic signaling in the neuroendocrine system. In particular, IgG were shown to play a role of peptide carriers and allosteric modulators of peptide receptors. Moreover, the pathway of discovery of the origin of α-MSH-reactive autoantibodies leads to the identification of a specific bacterial protein, ClpB, as an antigen mimetic of α-MSH, a key anorexigenic peptide. This discovery contributed to a better understanding of the role of the immune system in neuroendocrine communication between gut microbiota and the host and was further used for the development of a new generation of probiotics to control appetite. Furthermore, experimental data showed that an autoimmune reaction against ClpB, leading to the production of cross-reactive pathogenic α-MSH-reactive autoantibodies, may underlie the origin of eating disorders. Thus, in this chapter, we show that the characteristics of autoantibodies reacting with peptide hormones may provide valuable data that help to better understand the molecular mechanisms of neuroendocrine communication and to create therapeutic approaches for altered motivated behavior, response to stress and emotions.