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Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.

Variation in the human immune system is largely driven by non-heritable influences.

Author information

1
Science for Life Laboratory, Department of Medicine, Solna, Karolinska Institutet, 17121 Solna, Sweden; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94304, USA.
2
Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
3
Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94304, USA.
4
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94304, USA.
5
Department of Immunology, Faculty of Medicine, Technion, Haifa 31096, Israel.
6
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94304, USA.
7
Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA.
8
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94304, USA; Center for Pediatric Bioinformatics, Lucille Packard Children's Hospital, Stanford University, Stanford, CA 94304, USA.
9
Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94304, USA; Human Immune Monitoring Center, Stanford University School of Medicine, Stanford, CA 94304, USA.
10
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA; Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94304, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94304, USA. Electronic address: mmdavis@stanford.edu.

Abstract

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.

PMID:
25594173
PMCID:
PMC4302727
DOI:
10.1016/j.cell.2014.12.020
[Indexed for MEDLINE]
Free PMC Article
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