Publications

The goal of this study is to investigate factors that contribute to human immune variation. Prior studies have identified genetic, infectious, and biological associations with immune system competence and disease severity; however, there have been few integrative analyses of these factors and study populations are often limited in demographic diversity (age, sex, ancestry, etc.). While still informative, it is impossible to ascertain the scope of immune variation in the human population when studies are focused on only specific subsets of the human population and limited observed factors to analyze.

In this study, we quantify the contribution of intrinsic and extrinsic host factors on the setpoint of baseline (un-infected) immunity, and the magnitude and quality of the immune response to influenza infection in diverse populations around the world. This project includes samples from 1,705 healthy or influenza infected subjects from 5 countries and 8 distinct populations. North American populations include the Memphis cohort and the Baltimore cohort. Latin American populations include the Nicaragua cohort and the Colombia cohorts, which include subjects from the local city of Calabazo and two indigenous populations, Seywiaka and Umandita. Samples also include a European cohort from Belgium and an Asian cohort from Taiwan.

Putative determinants of immunity include: age, gender, genetics, race/ethnicity, and prior infectious exposures (herpesviruses). Measures of the immune system include characterization of immune cells, their functional responses, and immune products that mediate responses to infection. For influenza infected subjects, outcome measures include presence/absence of symptoms, symptom severity scores, amount of virus present in a patient, and duration of influenza virus production. To explain variation in these measures, regression modeling was utilized, which allows for an easily interpretable and transparent integrative analysis of all independent variables and a quantification of their unique, interactive, and collective effects on the immune measure of interest.