Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging

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Abstract

While many age-associated immune changes have been reported, a comprehensive set of metrics of immune aging is lacking. Here we report data from 243 healthy adults aged 40–97, for whom we measured clinical and functional parameters, serum cytokines, cytokines and gene expression in stimulated and unstimulated PBMC, PBMC phenotypes, and cytokine-stimulated pSTAT signaling in whole blood. Although highly heterogeneous across individuals, many of these assays revealed trends by age, sex, and CMV status, to greater or lesser degrees. Age, then sex and CMV status, showed the greatest impact on the immune system, as measured by the percentage of assay readouts with significant differences. An elastic net regression model could optimally predict age with 14 analytes from different assays. This reinforces the importance of multivariate analysis for defining a healthy immune system. These data provide a reference for others measuring immune parameters in older people.

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Most cited references 16

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Measurement of patient outcome in arthritis.

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A structure for representation of patient outcome is presented, together with a method for outcome measurement and validation of the technique in rheumatoid arthritis. The paradigm represents outcome by five separate dimensions: death, discomfort, disability, drug (therapeutic) toxicity, and dollar cost. Each dimension represents an outcome directly related to patient welfare. Quantitation of these outcome dimensions may be performed at interview or by patient questionnaire. With standardized, validated questions, similar scores are achieved by both methods. The questionnaire technique is preferred since it is inexpensive and does not require interobserver validation. These techniques appear extremely useful for evaluation of long term outcome of patients with rheumatic diseases.

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Sex is an independent prognostic indicator for survival and relapse/progression-free survival in metastasized stage III to IV melanoma: a pooled analysis of five European organisation for research and treatment of cancer randomized controlled trials.

Arjen Joosse, Sandra Collette, Stefan Suciu … (2013)

To study sex differences in survival and progression in patients with stage III or IV metastatic melanoma and to compare our results with published literature. Data were retrieved from three large, randomized, controlled trials of the European Organisation for Research and Treatment of Cancer in patients with stage III and two trials in patients with stage IV melanoma. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for females compared with males, adjusted for different sets of confounders for stage III and stage IV, respectively. In 2,734 stage III patients, females had a superior 5-year disease-specific survival (DSS) rate compared with males (51.5% v 43.3%), an adjusted HR for DSS of 0.85 (95% CI, 0.76 to 0.95), and an adjusted HR for relapse-free survival of 0.86 (95% CI, 0.77 to 0.95). In 1,306 stage IV patients, females also exhibited an advantage in DSS (2-year survival rate, 14.1% v 19.0%; adjusted HR, 0.81; 95% CI, 0.72 to 0.92) as well as for progression-free survival (adjusted HR, 0.79; 95% CI, 0.70 to 0.88). This female advantage was consistent across pre- and postmenopausal age categories and across different prognostic subgroups. However, the female advantage seems to become smaller in patients with higher metastatic tumor load. The persistent independent female advantage, even after metastasis to lymph nodes and distant sites, contradicts theories about sex behavioral differences as an explanation for this phenomenon. A biologic sex trait seems to profoundly influence melanoma progression and survival, even in advanced disease.

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Author and article information

Contributors

Derya Unutmaz: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 21 July 2015

Publication date Collection: 2015

Volume: 10

Issue: 7

Electronic Location Identifier: e0133627

Affiliations

[1 ]Institute for Immunity, Transplantation, and Infection, Stanford School of Medicine, Stanford University, Stanford, CA, United States of America

[2 ]Division of Rheumatology and Immunology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States of America

[3 ]CytoAnalytics, Denver, CO, United States of America

[4 ]Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States of America

Jackson Laboratory, UNITED STATES

Author notes

Competing Interests: JS is an employee of CytoAnalytics. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: HTM CGF JG EK CW. Performed the experiments: HWD. Analyzed the data: CCW JS AMN AAA HTM CGF. Wrote the paper: CCW HTM.

[¤]

Current Address: School of Chemistry and Biotechnology Engineering, University of Science & Technology Beijing, Beijing, 100083, China

* E-mail: Maecker@ 123456stanford.edu

Article

Publisher ID: PONE-D-15-14269

DOI: 10.1371/journal.pone.0133627

PMC ID: 4509650

PubMed ID: 26197454

SO-VID: fa6aa0ac-e50b-4b54-b28b-7dcb59441fc6

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

History

Date received : 2 April 2015

Date accepted : 29 June 2015

Page count

Figures: 8, Tables: 2, Pages: 21

Funding

This work was supported by grant 1RC4AG039014 from the National Institute on Aging, National Institutes of Health. JS (CytoAnalytics) performed data analysis as work-for-hire, which was paid for from grant funds. JS did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of all authors are articulated in the 'author contributions' section.

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Data Availability Data are available at: https://immport.niaid.nih.gov (SDY420). Please select dataset called 'Immunobiology of Aging".

Large-Scale and Comprehensive Immune Profiling and Functional Analysis of Normal Human Aging

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Most cited references 16

Measurement of patient outcome in arthritis.

Frailty in older adults: evidence for a phenotype

Sex is an independent prognostic indicator for survival and relapse/progression-free survival in metastasized stage III to IV melanoma: a pooled analysis of five European organisation for research and treatment of cancer randomized controlled trials.

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