The specific aims of the Milieu Intérieur project are to define the naturally-occurring variability of human immune responses, to assess how this variation is controlled by genomic and/or environmental factors, and to understand how this genetic/phenotypic variation may account for differences in susceptibility to infection, therapeutic treatment or vaccine response. The Milieu Intérieur project is organized in four stages.
Stage I Foundation phase (completed)
- Validation of whole blood immune stimulation assays for 27 stimulus conditions, using TruCulture® technology
- Design and approval of a clinical protocol for the recruitment of 1,000 healthy individuals stratified by age and gender
- Development of ten 8-color cytometry panels
- Building of a sample tracking solution
- Automation for sample handling and analysis pilot studies on all protocols
Stage II Consolidation phase (about to be completed)
- Recrutement of 1,000 healthy donors (first donor recruited September 17, 2012 — last donor recruited on August 8th, 2013)
- Constitution of a sample bank of whole blood culture supernatants, RNA from stimulated cells, genomic DNA, fecal samples, nasal swabs and punch biopsies across the whole cohort
- Generation and analysis of the cytometry and proteomic data
- Generation of the fibroblast lines from the punch biopsies
- Generation of the whole-genome genotyping data
- DNA methylation study in progress
Stage III Mechanistic studies (in progress)
- Molecular and biochemical evaluation of genotype–to–phenotype associations will be evaluated. For these studies there will be access to banked, annotated cell lines derived from the 1,000 person human subject study.
Stage IV Association studies in disease settings (in progress)
- Association studies in patient cohorts will link genetic diversity and immunologic phenotypes to disease states. Retrospective and prospective analysis of patient populations will be conducted accordingly. Additionally, this stage will involve the clinical validation of in vitro diagnostic and prognostic assays.