title: Variation in the human immune system is largely driven by non-heritable influences.
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.
authors.affiliation: 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.
authors.forename: Petter
authors.initials: P
authors.lastname: Brodin
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Jojic
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Gao
authors.affiliation: Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94304, USA.
authors.forename: Sanchita
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: 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.
authors.forename: Cesar J Lopez
authors.initials: CJ
authors.lastname: Angel
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Furman
authors.affiliation: Department of Immunology, Faculty of Medicine, Technion, Haifa 31096, Israel.
authors.forename: Shai
authors.initials: S
authors.lastname: Shen-Orr
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94304, USA.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
authors.affiliation: 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.
authors.forename: Atul J
authors.initials: AJ
authors.lastname: Butte
authors.affiliation: 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.
authors.forename: Holden T
authors.initials: HT
authors.lastname: Maecker
authors.affiliation: 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.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001798:Blood Proteins / Q000032:analysis / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D006801:Humans; D007109:Immunity; D007252:Influenza Vaccines / Q000276:immunology; D008875:Middle Aged; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D007252:Influenza Vaccines