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Darragh Duffy; Harnessing human diversity through the study of functional immune response biomarkers. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4768.
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Presentation Description :
Susceptibility to infections, disease severity, and response to vaccines are highly variable from one individual to another. Medical practices and public health policies typically take a ‘one size fits all’ model for disease management and vaccine development. This approach ignores individual heterogeneity in immune responses that likely impacts the response to therapy or the efficiency and development of side effects secondary to vaccine or treatment administration. Due to the complexity of immune responses at the individual and population level, it has been challenging thus far to define the borders of a healthy immune system as well as the parameters (genetic, epigenetic, and environmental) that drive its naturally-occurring variability. In particular, such assessments require large sample sizes, consensus for defining “healthy”, and standardized protocols for sample recruitment. In this context, the Milieu Interieur Consortium initiated in September 2012 a cross-sectional healthy population-based study of 1,000 healthy volunteers, split equally by sex (1:1 sex ratio) and stratified across five-decades of life. The overall aim of the Milieu Interieur study is to assess the factors underlying immunological variance within the general healthy population. The primary objective is to define genetic and environmental factors that contribute to the observed heterogeneity in immune responses. This is being realized through the characterization and integration of (i) lifestyle and medical history (ii) genome-wide SNP genotyping and whole-exome sequencing (iii) metagenomic diversity in fecal and nasal samples; (iv) induced transcriptional and protein signatures by diverse immune stimuli (v) variability in circulating immune cell populations based on flow cytometry. In parallel disease specific immune perturbations in infection and autoimmunity have been identified utilizing the same standardized approach. Direct comparison with our well defined 1,000 healthy donor cohort is allowing for a new understanding of these mechanisms in disease. In summary, these results will lay the foundations for the integration of immune response variability in smart clinical study design and eventually precision medicine strategies.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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