Frontiers in Immunology (Jul 2022)

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

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

DOI
https://doi.org/10.3389/fimmu.2022.919802
Journal volume & issue
Vol. 13

Abstract

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BackgroundOxidized 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.MethodsWe 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-PGE1 (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-PGF1α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE4). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy.ResultsPGE-M and LTE4 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 LTE4 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 LTE4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status.ConclusionThe 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.

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