Mycobacterium tuberculosis-Specific T-Cell Responses Are Impaired During Late Pregnancy With Elevated Biomarkers of Tuberculosis Risk Postpartum. (20th December 2021)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of infectious diseases. Volume 225:Number 9(2022)
• Page Start: 1663
• Page End: 1674
• Publication Date: 2021-12-20
• Subjects: M. tuberculosis -- pregnancy -- T-cell activation -- T-cell memory -- T cells; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab614
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: 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. Methods: 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. Results: 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. Conclusions: 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. Clinical Trials Registration: NCT0557245. Abstract : Pregnancy is a risk factor for tuberculosis disease. The influence of pregnancy on Mycobacterium tuberculosis -specific T-cell responses is unknown. M. tuberculosis -specific CD4 + T-cell responses were selectively diminished and simplified in the third trimester of pregnancy.