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- Title
Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum.
- Authors
Saha, Aparajita; Escuduero, Jaclyn; Layouni, Troy; Richardson, Barbra; Hou, Sharon; Mugo, Nelly; Mujugira, Andrew; Celum, Connie; Baeten, Jared M; Lingappa, Jairam; John-Stewart, Grace C; LaCourse, Sylvia M; Shah, Javeed A
- Abstract
<bold>Background: </bold>Pregnancy is a risk factor for progression from latent tuberculosis infection to symptomatic tuberculosis. However, how pregnancy influences T-cell responses to Mycobacterium tuberculosis is unknown.<bold>Methods: </bold>We measured M. tuberculosis-specific cytokines, T-cell memory markers, and overall CD4+ and CD8+ T-cell activation by flow cytometry from 49 women (18 with and 31 without HIV) who became pregnant while enrolled in a randomized controlled trial of preexposure prophylaxis for HIV. We analyzed data using COMPASS, an established statistical method for evaluating overall antigen-specific T-cell responses.<bold>Results: </bold>Pregnant women with latent tuberculosis infection demonstrated significantly diminished M. tuberculosis-specific CD4+ cytokine responses in the third trimester (COMPASS polyfunctional score [PFS], 0.07) compared before (PFS, 0.15), during (PFS, 0.13 and 0.16), and after pregnancy (PFS, 0.14; P = .0084, Kruskal-Wallis test). Paradoxically, M. tuberculosis-specific CD8+ cytokines and nonspecifically activated T-cells increased during late pregnancy. Nonspecific T-cell activation, a validated biomarker for progression from latent tuberculosis infection to tuberculosis disease, increased in latent tuberculosis infection-positive women postpartum, compared with latent tuberculosis infection-negative women.<bold>Conclusions: </bold>Pregnancy-related functional T-cell changes were most pronounced during late pregnancy. Both M. tuberculosis-specific T-cell changes during pregnancy and increases in immune activation postpartum may contribute to increased risk for tuberculosis progression.<bold>Clinical Trials Registration: </bold>NCT0557245.
- Subjects
LATENT tuberculosis; TUBERCULOSIS; T cells; MYCOBACTERIUM tuberculosis; CLINICAL trial registries; EXPOSURE therapy; PRENATAL depression; HIV infections; CYTOKINES; RESEARCH; RESEARCH methodology; EVALUATION research; COMPARATIVE studies; RANDOMIZED controlled trials; PUERPERIUM; RESEARCH funding
- Publication
Journal of Infectious Diseases, 2022, Vol 225, Issue 9, p1663
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiab614