Aparajita Saha1,2, Jaclyn Escuduero2, Troy Layouni3, Barbra Richardson2,4, Sharon Hou2, Nelly Mugo5, Andrew Mujugira2,6, Connie Celum1,2,7, Jared M Baeten2,8, Jairam Lingappa1,2,4, Grace C John-Stewart1,2,7,9, Sylvia M LaCourse1,2, Javeed A Shah1,2,3. 1. Department of Medicine, University of Washington, Seattle, Washington, USA. 2. Department of Global Health, University of Washington, Seattle, Washington, USA. 3. VA Puget Sound Health Care System, Seattle, Washington, USA. 4. Department of Biostatistics, University of Washington, Seattle, Washington, USA. 5. Kenya Medical Research Institute, Nairobi, Kenya. 6. Infectious Diseases Institute, Makerere University, Kampala, Uganda. 7. Department of Pediatrics, University of Washington, Seattle, Washington, USA. 8. Gilead Sciences, Foster City, California, USA. 9. Department of Epidemiology, University of Washington, Seattle, Washington, USA.
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.
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.
Authors: Philana Ling Lin; Tara Rutledge; Angela M Green; Matthew Bigbee; Carl Fuhrman; Edwin Klein; JoAnne L Flynn Journal: AIDS Res Hum Retroviruses Date: 2012-05-04 Impact factor: 2.205
Authors: David M Lewinsohn; Ian S Tydeman; Marisa Frieder; Jeff E Grotzke; Rebecca A Lines; Sheela Ahmed; Kamm D Prongay; Steven L Primack; Lois M A Colgin; Anne D Lewis; Deborah A Lewinsohn Journal: Microbes Infect Date: 2006-08-14 Impact factor: 2.700
Authors: I Sauzullo; R Scrivo; F Mengoni; A Ermocida; M Coppola; G Valesini; V Vullo; C M Mastroianni Journal: Clin Exp Immunol Date: 2014-06 Impact factor: 4.330