RT Journal Article
SR Electronic
T1 Ghrelin-Reactive Autoantibodies are elevated in Children with Prader-Willi Syndrome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 093930
DO 10.1101/093930
A1 Gabrielle Crisp
A1 Ohn Nyunt
A1 Lisa Chopin
A1 Inge Seim
A1 Mark Harris
A1 Penny Jeffery
YR 2016
UL http://biorxiv.org/content/early/2016/12/16/093930.abstract
AB Prader-Willi Syndrome (PWS) is a complex genetic disorder characterized by developmental and growth abnormalities, insatiable appetite, and excessive eating (hyperphagia). The underlying cause of hyperphagia in PWS is currently unknown, however, elevated levels of the peptide hormone ghrelin is believed to contribute. Recently, ghrelin-reactive autoantibodies (isotype IgG) were identified in non-genetic obesity. These autoantibodies act as ghrelin carrier proteins and potentiate its orexigenic effects. Here, we describe the identification of ghrelin-reactive autoantibodies in a cohort of 16 children with PWS. In comparison to unaffected siblings, autoantibody levels are significantly increased in PWS children. We further show that autoantibody levels are unaffected by food intake, unlike plasma ghrelin which declines postprandially in both groups. Critically, we also demonstrate that the autoantibodies bind the major circulating ghrelin isoforms, unacylated ghrelin, which does not stimulate appetite, and the orexigen acylated ghrelin. In excess, unacylated ghrelin may compete with acylated ghrelin for autoantibody binding. Taken together, this is the first report on ghrelin-reactive antibodies in a pediatric population, and the first to demonstrate that the antibodies do not discriminate between orexigenic and non-orexigenic ghrelin isoforms. Our work suggests that ghrelin autoantibodies can be targeted using non-orexigenic forms of ghrelin, thereby providing a novel therapeutic target for PWS and for obesity in general.