The plasma kynurenine-to-tryptophan ratio as a biomarker of tuberculosis disease in people living with HIV on antiretroviral therapy: an exploratory nested case-control study.

Autor: Gatechompol S; HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. sivaporn.k@hivnat.org.; Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. sivaporn.k@hivnat.org.; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands. sivaporn.k@hivnat.org., Lutter R; Department of Experimental Immunology, Amsterdam UMC and Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, The Netherlands.; Department of Pulmonary Diseases, Amsterdam UMC, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands., Vaz FM; Department of Core Facility Metabolomics, Amsterdam UMC, Amsterdam, The Netherlands.; Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., Ubolyam S; HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.; Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Avihingsanon A; HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.; Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Kerr SJ; HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.; Biostatistics Excellence Centre, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., van Leth F; Department of Health Sciences, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands., Cobelens F; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers Location University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2024 Apr 02; Vol. 24 (1), pp. 372. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1186/s12879-024-09258-4
Abstrakt: Background: Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobacterial survival. The plasma Kyn-to-Trp (K/T) ratio is a potential TB diagnostic and/or predictive biomarker in PWH on long-term antiretroviral therapy (ART).
Methods: We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry.
Results: The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069-0.123) compared to controls (0.055; IQR 0.045-0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB (p = 0.005), but there was no correlation in controls.
Conclusions: The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts.
Trial Registration: ClinicalTrials.gov Identifier: NCT00411983.
(© 2024. The Author(s).)
Databáze: MEDLINE
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