AUTHOR=Arriaga María B. , Karim Farina , Queiroz Artur T.L. , Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Sales Caio , Moosa Mahomed-Yunus S. , Mazibuko Matilda , Milne Ginger L. , Maruri Fernanda , Serezani Carlos Henrique , Koethe John R. , Figueiredo Marina C. , Kritski Afrânio L. , Cordeiro-Santos Marcelo , Rolla Valeria C. , Sterling Timothy R. , Leslie Alasdair , Andrade Bruno B. ,  the RePORT Brazil and South Africa consortia , Andrade Alice M. S. , Rocha Michael S. , Nascimento Vanessa , Cubillos-Angulo Juan M. , Malta-Santos Hayna , Rebouças-Silva Jéssica , Viana Sayonara M. , Santos Saulo R. N. , Ramos André , Costa Alysson G. , Silva Jaquelane , Secretaria Jamile G. de Oliveira, , Benjamin Aline , Gomes-Silva Adriano , Sant’Anna Flavia M. , Ignácio Francine P. , Lourenço Maria Cristina , Silva Elisangela C. , Moreira Adriana S. R. , Mello Mayla 

TITLE=Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.919802

DOI=10.3389/fimmu.2022.919802

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>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 <italic>M. tuberculosis</italic> (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.</p></sec><sec><title>Methods</title><p>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<sub>1</sub> (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<sub>1</sub>α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE<sub>4</sub>). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy.</p></sec><sec><title>Results</title><p>PGE-M and LTE<sub>4</sub> values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p&lt;0.001). In addition, there was a significant decrease in PGI-M and LTE<sub>4</sub> 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<sub>4</sub> at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>