{"doi":"10.3389/fimmu.2020.01796","title":"Requisite Omega-3 HUFA Biomarker Thresholds for Preventing Murine Lupus Flaring","abstract":"Lupus is a systemic autoimmune disease typified by uncontrolled inflammation, disruption of im-mune tolerance, and intermittent flaring – events triggerable by environmental factors. Preclinical and clinical studies reveal that consumption of the marine ω-3 highly unsaturated fatty acids (HU-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) might be used as a precision nutrition intervention to lessen lupus symptoms. The anti-inflammatory and pro-resolving effects of -3 HUFAs are inextricably linked to their presence in membrane phospholipids. The -3 HUFA score, calculated as [100  (-3 HUFAs/(-3 HUFAs + -6 HUFAs))] in red blood cells (RBCs), and the Omega-3 Index (O3I), calculated as [100  ((DHA+EPA)/total fatty acids)] in RBCs, are two biomarkers potentially amenable to relating tissue HUFA balance to clinical out-comes in individuals with lupus. Using data from three prior preclinical DHA supplementation studies, we tested the hypothesis that the -3 HUFA score and the O3I inversely correlate with indicators of autoimmune pathogenesis in the cSiO2-triggered lupus flaring model. The three studies employed both low and high fat rodent diets, as well as more complex diets emulating the U.S. dietary pattern. The -3 HUFA scores in RBCs were comparatively more robust than the O3I at predicting HUFA balances in the kidney, liver, spleen, and lung. Importantly, increases in both the -3 HUFA score (>40%) and the O3I (>10%) were strongly associated with suppression of cSiO2-triggered 1) expression of interferon-regulated genes, proinflammatory cytokine production, leukocyte infiltration, and ectopic lymphoid structure development in the lung, 2) pulmonary and systemic autoantibody production, and 3) glomerulonephritis. Collectively, these findings identify achievable -3 HUFA scores and O3I thresholds that could be targeted in future human intervention studies querying how -3 HUFA consumption influences lupus and other autoimmune dis-eases.","journal":"Frontiers in Immunology","year":2020,"id":68540,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":363439,"name":"Rita S. Strakovsky","orcid":"0000-0002-3551-1615","position":1,"is_corresponding":false},{"id":332566,"name":"Abby D. Benninghoff","orcid":"0000-0002-7993-0117","position":2,"is_corresponding":false},{"id":332560,"name":"Lichchavi D. Rajasinghe","orcid":"0000-0002-5136-7422","position":3,"is_corresponding":false},{"id":363440,"name":"A.L. Lock","orcid":"0000-0002-9282-399X","position":4,"is_corresponding":false},{"id":313892,"name":"Jack R. Harkema","orcid":"0000-0003-4682-0824","position":5,"is_corresponding":false},{"id":332567,"name":"James J. Pestka","orcid":"0000-0003-4689-2756","position":6,"is_corresponding":false},{"id":332565,"name":"Kathryn A. Wierenga","orcid":"0000-0003-1725-4616","position":0,"is_corresponding":true}],"reference_count":108,"raw_metadata":null,"created_at":"2026-07-18T21:41:52.279368Z","pmid":"32973753","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":[]}