Cell
Volume 160, Issues 1–2, 15 January 2015, Pages 37-47
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Article
Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences

https://doi.org/10.1016/j.cell.2014.12.020Get rights and content
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Highlights

  • Non-heritable influences explain much of the variation in immune measurements

  • Immune parameters become more divergent between MZ twins with increasing age

  • A single non-heritable factor affects more than 50% of all cell subsets and serum proteins

  • Heritable and non-heritable immune measurements are largely interdependent

Summary

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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