{"doi":"10.1101/2024.01.04.574253","title":"Blood-based targeted metabolipidomics reveals altered omega fatty acid-derived lipid mediators in relapsing-remitting multiple sclerosis patients","abstract":"Unresolved and uncontrolled inflammation is considered a hallmark of pathogenesis in chronic inflammatory diseases like multiple sclerosis (MS), suggesting a defective resolution process. Inflammatory resolution is an active process partially mediated by endogenous metabolites of dietary polyunsaturated fatty acids (PUFA), collectively termed specialized pro-resolving lipid mediators (SPMs). Altered levels of resolution mediators have been reported in several inflammatory diseases and may partly explain impaired inflammatory resolution. Performing LC-MS/MS-based targeted lipid mediator profiling, we observed distinct changes in fatty acid metabolites in serum from 30 relapsing-remitting MS (RRMS) patients relative to 30 matched healthy subjects (HS). Robust linear regression revealed 12 altered lipid mediators after adjusting for confounders (p <0.05). Of these, 15d-PGJ2, PGE3, and LTB5 were increased in MS while PGF2a, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 12-HEPE, 14-HDoHE, and DHEA were decreased in MS compared to HS. In addition, 12,13-DiHOME and 12,13-DiHODE were positively correlated with expanded disability status scale values (EDSS). Using Partial Least Squares, we identified several lipid mediators with high VIP scores (VIP > 1: 32% - 52%) of which POEA, PGE3, DHEA, LTB5, and 12-HETE were top predictors for distinguishing between RRMS and HS (AUC =0.75) based on the XGBoost Classifier algorithm. Collectively, these findings suggest an imbalance between inflammation and resolution. Altogether, lipid mediators appear to have potential as diagnostic and prognostic biomarkers for RRMS.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485836,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":794033,"name":"Jeffrey Waters","orcid":"0000-0002-5843-7710","position":1,"is_corresponding":false},{"id":1285379,"name":"Nasar Ata","orcid":null,"position":2,"is_corresponding":false},{"id":353977,"name":"Indrani Datta","orcid":"0000-0001-8864-473X","position":3,"is_corresponding":false},{"id":349079,"name":"Theresa L. Pedersen","orcid":null,"position":4,"is_corresponding":false},{"id":641731,"name":"Mirela Cerghet","orcid":"0000-0001-8884-6315","position":5,"is_corresponding":false},{"id":79896,"name":"Laila Poisson","orcid":"0000-0002-3409-6536","position":6,"is_corresponding":false},{"id":593313,"name":"Silva Markovic‐Plese","orcid":"0000-0002-0061-2707","position":7,"is_corresponding":false},{"id":269732,"name":"Ramandeep Rattan","orcid":"0000-0002-3532-6057","position":8,"is_corresponding":false},{"id":369919,"name":"Ameer Y. Taha","orcid":"0000-0003-4611-7450","position":9,"is_corresponding":false},{"id":245218,"name":"John W. Newman","orcid":"0000-0001-9632-6571","position":10,"is_corresponding":false},{"id":483230,"name":"Shailendra Giri","orcid":"0000-0002-7123-829X","position":11,"is_corresponding":false},{"id":488520,"name":"Insha Zahoor","orcid":"0000-0001-9919-1959","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:07:52.536246Z","pmid":"38260401","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}