@article{10.1172/jci.insight.130090, author = {Julius Müller AND Rachel Tanner AND Magali Matsumiya AND Margaret A. Snowden AND Bernard Landry AND Iman Satti AND Stephanie A. Harris AND Matthew K. O’Shea AND Lisa Stockdale AND Leanne Marsay AND Agnieszka Chomka AND Rachel Harrington-Kandt AND Zita-Rose Manjaly Thomas AND Vivek Naranbhai AND Elena Stylianou AND Stanley Kimbung Mbandi AND Mark Hatherill AND Gregory Hussey AND Hassan Mahomed AND Michele Tameris AND J. Bruce McClain AND Thomas G. Evans AND Willem A. Hanekom AND Thomas J. Scriba AND Helen McShane AND Helen A. Fletcher}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Cytomegalovirus infection is a risk factor for tuberculosis disease in infants}, year = {2019}, month = {12}, volume = {4}, url = {https://insight.jci.org/articles/view/130090}, abstract = {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 2 years of life, and 129 healthy matched controls, we found the cytomegalovirus-stimulated (CMV-stimulated) IFN-γ response 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+ infants who developed TB disease had lower expression of NK cell–associated gene signatures and a lower frequency of CD3–CD4–CD8– lymphocytes. We identified transcriptional signatures predictive of TB disease risk among CMV ELISpot–positive (area under the receiver operating characteristic [AUROC], 0.98, accuracy, 92.57%) and –negative (AUROC, 0.9; accuracy, 79.3%) infants; the CMV– signature was validated in an independent infant study (AUROC, 0.71; accuracy, 63.9%). A 16-gene signature that previously identified adolescents at risk of developing TB disease did not accurately classify case and control infants in this study. Understanding the microbial drivers of T cell activation, such as CMV, could guide new strategies for prevention of TB disease in infants.}, number = {23}, doi = {10.1172/jci.insight.130090}, url = {https://doi.org/10.1172/jci.insight.130090}, }