An integrative approach for studying immunological variation in an aging population – The Milieu Intérieur follow-up study

Human immune responses vary across individuals due to both genetic and environmental factors. We previously established the Milieu Intérieur cohort to define boundaries of healthy immune variation and identify their determinants. To evaluate how immune responses change over time and test whether immune states can predict future disease, we conducted a 10-year follow-up of the cohort. Here we show widespread changes in humoral responses to pathogens over this period, including unexpected seroreversion of cytomegalovirus (CMV) status, despite a general age-related increase in CMV antibodies. We also investigated whether immune profiles at initial recruitment are associated with disease development a decade later. Strikingly, whole blood transcriptional responses to Staphylococcus aureus and Candida albicans stimulation were predictive of subsequent infectious disease. Collectively, the Milieu Intérieur longitudinal study represents a valuable resource for evaluating immune aging and may help identify predictors of adverse health outcomes.