There is considerable heterogeneity in immunological parameters between individuals,
but its sources are largely unknown. To assess the relative contribution of heritable
versus non-heritable factors, we have performed a systems-level analysis of 210 healthy
twins between 8 and 82 years of age. We measured 204 different parameters, including
cell population frequencies, cytokine responses, and serum proteins, and found that
77% of these are dominated (>50% of variance) and 58% almost completely determined
(>80% of variance) by non-heritable influences. In addition, some of these parameters
become more variable with age, suggesting the cumulative influence of environmental
exposure. Similarly, the serological responses to seasonal influenza vaccination are
also determined largely by non-heritable factors, likely due to repeated exposure
to different strains. Lastly, in MZ twins discordant for cytomegalovirus infection,
more than half of all parameters are affected. These results highlight the largely
reactive and adaptive nature of the immune system in healthy individuals.
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