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

Human immune responses are highly variable from one individual to another, with these differences determined by both genetic and environmental factors. We previously established the Milieu Interieur cohort to define the boundaries of healthy immune responses and identify and quantify its different determinants. From this cohort of 1,000 well-defined healthy donors, we have identified multiple genetic and environmental factors that are associated with variable immune phenotypes. Crucially, these associations were observed in a healthy context, as defined by strict inclusion and exclusion criteria. To assess how such immune responses may vary over time, we initiated a 10-year follow-up clinical study of the cohort. From the original 1,000 donors, we identified and recruited 415 donors from whom we assessed recent medical history and lifestyle factors, in addition to collecting samples for measurement of diverse immune phenotypes. A comparison of 107 laboratory and serological measures over the 10-year period showed significant correlations, highlighting the quality of the data collected. By accounting for potential batch effects, our analyses revealed the profound effects of aging on health-related biomarkers and antibody levels against common pathogens. We determined that a significant proportion of the donors no longer meet the initial definition of good health, due to either physiological changes associated with aging, or disease incidence including cancer, autoimmune and cardiovascular diseases. We found that disease development over the past 10 years is associated with a biological aging score, assessed at the time of the initial recruitment. In summary, the Milieu Interieur follow-up study will provide new opportunities for studying biological mechanisms of immunosenescence and identifying factors associated with accelerated immune aging and poor health outcomes.