학술논문
Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis
Document Type
article
Author
María B. Arriaga; Farina Karim; Artur T.L. Queiroz; Mariana Araújo-Pereira; Beatriz Barreto-Duarte; 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; Valeria C. Rolla; Timothy R. Sterling; Alasdair Leslie; 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
Source
Frontiers in Immunology, Vol 13 (2022)
Subject
Language
English
ISSN
1664-3224
Abstract
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