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Rethinking immune studies: population-level immune variations and the path forward

Title: Rethinking immune studies: population-level immune variations and the path forward
Authors: Hysong, Micah R; Memili, Aylin; Delaney, Joseph A; Ekunwe, Lynette; Huber, Sally; Reiner, Alexander P; Patsy, Bruce M; Sitlani, Colleen M; Tracy, Russell P; Taylor, Kent D; Olson, Nels C; Doyle, Margaret F; Raffield, Laura M
Contributors: Duque, Gustavo; Cardiovascular Health; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute on Aging; National Center for Advancing Translational Sciences; Jackson State University; Tougaloo College; Mississippi State Department of Health; University of Mississippi Medical Center; National Institute on Minority Health and Health Disparities; NHLBI; National Institutes of Health, or the U.S. Department of Health and Human Services
Source: The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences ; volume 81, issue 4 ; ISSN 1079-5006 1758-535X
Publisher Information: Oxford University Press (OUP)
Publication Year: 2026
Description: Shifts in immune cell proportions underlie disease progression and immunotherapy response, positioning them as promising diagnostic biomarkers and therapeutic targets. However, these shifts also occur naturally across the lifespan and vary with demographic factors such as age and sex, which may complicate their interpretation and clinical utility. While demographic associations have been explored previously, there have been mixed results likely due to small sample sizes and cross-cohort population-specific differences. To address these limitations, we conducted a meta-analysis across 3 large, diverse cohort studies to evaluate associations between 20 immune cell subtypes, 3 informative cell ratios, and a range of sociodemographic variables such as age, sex, self-identified race and ethnicity (SIRE), and socioeconomic status. We find consistent and significant associations across all sociodemographic dimensions. Cytomegalovirus (CMV)—a key driver of immune senescence—emerged as a major contributor to variation in immune composition and CMV antibody levels were higher among women, individuals of lower socioeconomic status, and marginalized racial and ethnic groups. In addition, male sex showed similar patterns of association with immune profiles as aging, whereas race did not. These findings underscore the need to account for diverse sociodemographic factors in immunology study design and participant recruitment to avoid population-specific biases and ensure broadly generalizable results.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/gerona/glag055
DOI: 10.1093/gerona/glag055/67115188/glag055.pdf
Availability: https://doi.org/10.1093/gerona/glag055; https://academic.oup.com/biomedgerontology/advance-article-pdf/doi/10.1093/gerona/glag055/67115188/glag055.pdf; https://academic.oup.com/biomedgerontology/article-pdf/81/4/glag055/67115188/glag055.pdf
Rights: https://creativecommons.org/licenses/by-nc/4.0/
Accession Number: edsbas.F29D51D7
Database: BASE