New approach to determine the healthy immune variations by combining clustering methods

Immune-mediated infammatory diseases are characterized by variability in disease presentation
and severity but studying it is a challenging task. Defning the limits of a healthy immune system
is therefore a prior step to capture variability in disease conditions. The goal of this study is to
characterize the global immune cell composition along with their infuencing factors. Blood samples
were collected from 2 independent cohorts of respectively 389 (exploratory) and 208 (replication)
healthy subjects. Twelve immune cells were measured in blood together with biological parameters.
Three complementary clustering approaches were used to evaluate if variability related to the
immune cells could be characterized as clusters or as a continuum. Large coefcients of variation
confrmed the inter-individual variability of immune cells. Considering all subset variations in an
overall analysis, it appeared that the immune makeup was organized as a continuum through the
two cohorts. Some intrinsic and environmental factors afected the inter-individual variability of cells
but without unveiling separable groups with similar features. This study provides a framework based
on complementary clustering approach for analyzing inter-individual variability of immune cells. Our
analyses support the absence of clusters in our two healthy cohorts. Also, our study reports some
infuence of age, gender, BMI, cortisol, season and CMV infection on immune variability