Continuous immunotypes describe human immune variation and predict diverse responses

PNAS – Proceedings of the National Academy of Sciences of the United States
of America
[Accessed 15 July 2017]

Biological Sciences – Immunology and Inflammation – Physical Sciences – Biophysics and Computational Biology:
Continuous immunotypes describe human immune variation and predict diverse responses
Kevin J. Kaczorowski, Karthik Shekhar, Dieudonné Nkulikiyimfura, Cornelia L. Dekker, Holden Maecker, Mark M. Davis, Arup K. Chakraborty, and Petter Brodin
PNAS 2017 ; published ahead of print July 10, 2017, doi:10.1073/pnas.1705065114
The human immune system consists of many different white blood cells that coordinate their actions to fight infections. The balance between these cell populations is determined by direct interactions and soluble factors such as cytokines, which serve as messengers between cells. Understanding how the interactions between cell populations influence the function of the immune system as a whole will allow us to better distinguish patients most at risk for specific infections or immune-mediated diseases and inform vaccination strategies. Here, we determine key collective interactions between white blood cells present in blood samples taken from healthy individuals. This perspective allows us to predict functional responses and describe previously unappreciated differences between age groups and in individuals carrying cytomegalovirus.
The immune system consists of many specialized cell populations that communicate with each other to achieve systemic immune responses. Our analyses of various measured immune cell population frequencies in healthy humans and their responses to diverse stimuli show that human immune variation is continuous in nature, rather than characterized by discrete groups of similar individuals. We show that the same three key combinations of immune cell population frequencies can define an individual’s immunotype and predict a diverse set of functional responses to cytokine stimulation. We find that, even though interindividual variations in specific cell population frequencies can be large, unrelated individuals of younger age have more homogeneous immunotypes than older individuals. Across age groups, cytomegalovirus seropositive individuals displayed immunotypes characteristic of older individuals. The conceptual framework for defining immunotypes suggested by our results could guide the development of better therapies that appropriately modulate collective immunotypes, rather than individual immune components.