Article
Effect of dysglycemia on urinary lipid mediator profiles in persons with pulmonary tuberculosis
Registro en:
ARRIAGA, María B. et al. Effect of dysglycemia on urinary lipid mediator profiles in persons with pulmonary tuberculosis. Frontiers in Immunology, v. 13, p. 1-12, 8 July 2022.
1664-3224
10.3389/fimmu.2022.919802
1664-3224
Autor
Arriaga, María B.
Karim, Farina
Queiroz, Artur T. L.
Pereira, Mariana Araújo
Duarte, Beatriz Barreto
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.
Santos, Marcelo Cordeiro
Rolla, Valeria C.
Sterling, Timothy R.
Leslie, Alasdair
Andrade, Bruno B.
Resumen
Departamento de Ciência e Tecnologia (DECIT).
Secretaria de Ciência e Tecnologia (SCTIE).
Ministério da Saúde (MS).
Institutos Nacionais de Alergia e Doenças Infecciosas.
U.S. Civilian Research and Development (CRDF).
Programa de Pesquisa Intermural da Fundação Oswaldo Cruz.
Programa de Pesquisa Intermural da Fundação José Silveira.
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB).
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Secretaria de Ciência e Tecnologia (SCTIE) Ministério da Saúde (MS) Institutos Nacionais de Alergia e Doenças Infecciosas U.S. Civilian Research and Development (CRDF) Programa de Pesquisa Intermural da Fundação Oswaldo Cruz Programa de Pesquisa Intermural da Fundação José Silveira Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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 subgroups with or without dysglycemia at baseline. Participants were enrolled from RePORTBrazil (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) TBnormoglycemia (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-hydroxy11,15-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. Results: PGE-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. Conclusion: The urinary eicosanoid metabolite profile was associated with TBdysglycemia 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.