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High throughput plasma proteomics profiling reveals metabolic and immunologic differences between anorexia nervosa subtypes

ABSTRACT: Anorexia nervosa (AN) is a severe psychiatric disorder of an unknown aetiology with a mortality rate of 5% per year, making it one of the most deadly of all psychiatric illnesses. Despite extensive research efforts in recent years, 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 plasma samples from 77 females with AN (56 restrictive and 21 binge-purge type) and 70 healthy controls. Using state-of-the-art mass spectrometry-based proteomics technology in conjunction with an advanced bioinformatics pipeline, we quantify more than 500 plasma proteins. Our differential expression analysis and correlation of proteomics data with clinical parameters 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 dysregulation of plasma cells in AN patients. Additionally, we stratified AN patients based on the quantified proteins and suggest potential auto-immune nature of disease in restrictive subtype. In summary, this study provides a comprehensive map of plasma proteins that may have utility in further understanding the pathophysiology of AN.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Anorexia Nervosa

SUBMITTER: Diana Samodova-Sommer

LAB HEAD: Atul Shahaji Deshmukh

PROVIDER: PXD040038 | Pride | 2024-01-10

REPOSITORIES: Pride

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Project description:The biology and physiology of Siberian sturgeon reproduction differ substantially from teleost fish. Seminal plasma support and protect the viability, motility and fertilizing capacity of spermatozoa by creating the optimal environment for the storage. The present study for the first time described in-depth proteomic characterization of Siberian sturgeon seminal plasma using gel based and gel-free proteomic approaches: LC-MS/MS, 2DE and 2D blue native (BN)/SDS-PAGE. LC-MS/MS allowed to identify 657 proteins, which were classified according to their functions and pathways. 2DE visualized 339 spots corresponding to 76 unique proteins (almost 60% were present in various proteoforms). For the first time we demonstrated interactions between seminal proteins; four (C1-C4) multiprotein complexes were identified after 2D BN/SDS-PAGE; composed of (C1) serotransferrin-2 (TF) and fish-egg lectin (FEL); (C2) serum albumin 2 (ALB) and retinol-binding protein 4 (RBP4); (C3) ALB and TF (C3) and (C4) apolipoprotein A-I (APOA1), riboflavin-binding protein (RfBP) and myoglobin (MB). BN-SDS-PAGE also revealed that immunoglobulin and TF formed homomultimeric (dimer, trimer, tetramer and pentamer) complexes in seminal plasma. ALB, TF, Beta-Ala-His dipeptidase, glyceraldehyde-3-phosphate dehydrogenase, IGH, APOA1, hemopexin, type-4 ice-structuring protein, FEL, RfBP and glycogen phosphorylase, liver form-like were selected as major seminal plasma proteins. The functional analysis of identified proteins indicated their involvement mainly in immune system process and response to stimulus, metabolism, vesicle-mediated transport, proteolysis, and catherin binding involved in cell-cell adhesion. Moreover, 67 proteins were associated with reproductive processes, including spermatogenesis, fertilization, acrosomal reaction and sperm motility. Comparative proteomic analysis of sturgeon seminal plasma showed common proteins with fish and human and 150 proteins specific for sturgeon which may reflect the specificity of sturgeon reproduction. To conclude, this integrative proteomic view lead to deeper insight into physiological function of seminal plasma and processes occurred in sturgeon reproductive tract.

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High throughput plasma proteomics profiling reveals metabolic and immunologic differences between anorexia nervosa subtypes

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