The Milieu Intérieur study — An integrative approach for study of human immunological variance

Abstract

The Milieu Intérieur Consortium has established a 1000-person healthy population-based study (stratified according to sex and age), creating an unparalleled opportunity for assessing the determinants of human immunologic variance. Herein, we define the criteria utilized for participant enrollment, and highlight the key data that were collected for correlative studies. In this report, we analyzed biological correlates of sex, age, smoking-habits, metabolic score and CMV infection. We characterized and identified unique risk factors among healthy donors, as compared to studies that have focused on the general population or disease cohorts. Finally, we highlight sex-bias in the thresholds used for metabolic score determination and recommend a deeper examination of current guidelines. In sum, our clinical design, standardized sample collection strategies, and epidemiological data analyses have established the foundation for defining variability within human immune responses.

Deconvolution of the Response to Bacillus Calmette–Guérin Reveals NF-κB-Induced Cytokines As Autocrine Mediators of Innate Immunity

“…Details are provided in Ref. (11) and information about the cohort was registered at (identifier NCT01699893). Data presented in Figures 3–7 were obtained using fresh whole blood from healthy volunteers, collected in heparin coagulant tubes, and procured from Etablissement Français du Sang (EFS).…”

Milieu intérieur: Defining the boundaries of a healthy immune response for improved vaccination strategies

“…It was within this context that the Milieu Interieur consortium was established in 2011 to define the normal boundaries of a healthy immune response in a European population, and to define their genetic and environmental determinants. 3 Additional complementary healthy human cohorts have been established in parallel to address similar questions that include the Human Functional Genomics Project, 4 the Human Immunology Project Consortium (HIPC), 5 " and the 10K Immunomes. 6 From these studies we are now beginning to obtain a better definition of immune response variability and the key factors that drive it.…”

Immune response biomarkers in human and veterinary research

“…Comparative Immunology, Microbiology and Infectious Diseases 59 (2018) [57][58][59][60][61][62] tb infection could help to overcome some important limitations of IGRAs, such as testing in young children or immunocompromised individuals [39,45,46]. This monokine-based reporter has been shown to be both sensitive and accurate in studying antigen-specific T cell responses.…”

“…One involves the utilisation of more standardised approaches for studying induced immune approaches [60]; and a second complementary approach comprises the use of multiple cytokine markers detected with multiplex assays instead of a single analyte for the identification of more robust signatures [61]. In addition, studies that will define the genetic and environmental contributions to such naturally occurring variability to provide reference range values will help to better identify real biological signals from background noise [62].…”