Plasma proteome profiling reveals metabolic and immunologic differences between Anorexia Nervosa subtypes

Aims/hypothesis: Anorexia Nervosa (AN) is a severe psychiatric disorder of an unknown etiology with a crude mortality rate of about 5 % per decade, making it one of the deadliest of all psychiatric illnesses. AN is broadly classified into two main subtypes, restricting and binge/purging disorder. Despite extensive research efforts during several decades, the underlying pathophysiology of AN remains poorly understood. In this study, we aimed to identify novel protein biomarkers for AN by performing a proteomics analysis of fasting plasma samples from 78 females with AN (57 restrictive and 21 binge/purge type) and 70 healthy controls. Methods: Using state-of-the-art mass spectrometry-based proteomics technology in conjunction with an advanced bioinformatics pipeline, we quantify >500 plasma proteins. Results: Differential expression analysis and correlation of proteomics data with clinical variables led to identification of a panel of novel protein biomarkers with potential pathophysiological significance for AN. Our findings demonstrate evidence of a humoral immune system response, altered lipid metabolism and potential alteration of plasma cells in AN patients. Additionally, we stratified AN patients based on the quantified proteins and suggest a potential autoimmune nature in the restrictive subtype of AN. Conclusions/interpretation: In summary, on top of biomarkers of AN subtypes, this study provides a comprehensive map of plasma proteins that constitute a resource for further studies of the pathophysiology of AN.