RT Journal Article
SR Electronic
T1 Cytomegalovirus infection is a risk factor for TB disease in Infants
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 222646
DO 10.1101/222646
A1 Julius Muller
A1 Rachel Tanner
A1 Magali Matsumiya
A1 Margaret A. Snowden
A1 Bernard Landry
A1 Iman Satti
A1 Stephanie A. Harris
A1 Rachel Tanner
A1 Matthew K. O’Shea
A1 Lisa Stockdale
A1 Leanne Marsay
A1 Agnieszka Chomka
A1 Rachel Harrington-Kandt
A1 Zita-Rose Manjaly Thomas
A1 Vivek Naranbhai
A1 Elena Stylianou
A1 Stanley Kimbung Mbandi
A1 Mark Hatherill
A1 Gregory Hussey
A1 Hassan Mahomed
A1 Michele Tameris
A1 J. Bruce McClain
A1 Thomas G. Evans
A1 Willem A. Hanekom
A1 Thomas J. Scriba
A1 Helen McShane
A1 Helen A. Fletcher
YR 2019
UL http://biorxiv.org/content/early/2019/05/06/222646.abstract
AB Immune activation is associated with increased risk of tuberculosis (TB) disease in infants. We performed a case-control analysis to identify drivers of immune activation and disease risk. Among 49 infants who developed TB disease over the first two years of life, and 129 matched controls who remained healthy, we found the cytomegalovirus (CMV) stimulated IFN-γ response at age 4-6 months to be associated with CD8+ T-cell activation (Spearman’s rho, p=6×10−8). A CMV specific IFN-γ response was also associated with increased risk of developing TB disease (Conditional Logistic Regression, p=0.043, OR 2.2, 95% CI 1.02-4.83), and shorter time to TB diagnosis (Log Rank Mantel-Cox p=0.037). CMV positive infants who developed TB disease had lower expression of natural killer cell associated gene signatures and a lower frequency of CD3-CD4-CD8-lymphocytes. We identified transcriptional signatures predictive of risk of TB disease among CMV ELISpot positive (AUROC 0.98, accuracy 92.57%) and negative (AUROC 0.9, accuracy 79.3%) infants; the CMV negative signature validated in an independent infant study (AUROC 0.71, accuracy 63.9%). Understanding and controlling the microbial drivers of T cell activation, such as CMV, could guide new strategies for prevention of TB disease in infants.