{"doi":"10.3389/fimmu.2022.919802","title":"Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis","abstract":"Background Oxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of M. tuberculosis (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses. Methods We conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had sub-groups with or without dysglycemia at baseline. Participants were enrolled from RePORT-Brazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TB-normoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE 1 (metabolite of PGE2, TN-E), 9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF 1 α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE 4 ). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy. Results PGE-M and LTE 4 values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p<0.001). In addition, there was a significant decrease in PGI-M and LTE 4 levels from baseline to month 6 in the TB-dysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE 4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status. Conclusion The urinary eicosanoid metabolite profile was associated with TB-dysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia.","journal":"Frontiers in Immunology","year":2022,"id":290196,"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":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":406977,"name":"Farina Karim","orcid":"0000-0001-9698-016X","position":1,"is_corresponding":false},{"id":382615,"name":"Artur T. L. Queiroz","orcid":"0000-0003-4908-9993","position":2,"is_corresponding":false},{"id":479093,"name":"Mariana Araújo‐Pereira","orcid":"0000-0002-1141-1580","position":3,"is_corresponding":false},{"id":517545,"name":"Beatriz Barreto‐Duarte","orcid":"0000-0002-9901-8328","position":4,"is_corresponding":false},{"id":828855,"name":"Caio Sales","orcid":null,"position":5,"is_corresponding":false},{"id":282139,"name":"Mahomed‐Yunus S. Moosa","orcid":"0000-0001-6191-4023","position":6,"is_corresponding":false},{"id":498499,"name":"Matilda Mazibuko","orcid":null,"position":7,"is_corresponding":false},{"id":297595,"name":"Ginger L. Milne","orcid":"0000-0003-3890-151X","position":8,"is_corresponding":false},{"id":311221,"name":"Fernanda Maruri","orcid":"0000-0001-9533-8239","position":9,"is_corresponding":false},{"id":489990,"name":"C. Henrique Serezani","orcid":"0000-0002-5363-415X","position":10,"is_corresponding":false},{"id":240259,"name":"John R. Koethe","orcid":"0000-0001-6490-6942","position":11,"is_corresponding":false},{"id":689804,"name":"Marina C. Figueiredo","orcid":"0000-0002-0671-398X","position":12,"is_corresponding":false},{"id":110663,"name":"Afranio Kritski","orcid":"0000-0002-5900-6007","position":13,"is_corresponding":false},{"id":689803,"name":"Marcelo Cordeiro‐Santos","orcid":"0000-0002-7140-7145","position":14,"is_corresponding":false},{"id":689805,"name":"Valéria C. Rolla","orcid":"0000-0002-0841-1408","position":15,"is_corresponding":false},{"id":240257,"name":"Timothy R. Sterling","orcid":"0000-0002-4822-6979","position":16,"is_corresponding":false},{"id":104353,"name":"Alasdair Leslie","orcid":"0000-0003-2538-6467","position":17,"is_corresponding":false},{"id":252301,"name":"Bruno B. Andrade","orcid":"0000-0001-6833-3811","position":18,"is_corresponding":false},{"id":972599,"name":"the RePORT Brazil and South Africa consortia","orcid":null,"position":19,"is_corresponding":false},{"id":341772,"name":"María B. Arriaga","orcid":"0000-0001-6883-8422","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T00:30:26.667578Z","pmid":"35874781","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":[]}