Circulating Immune-Cell Profiles and Diffuse Idiopathic Skeletal Hyperostosis: A Community-Based Cross-Sectional Study

Objectives: Diffuse idiopathic skeletal hyperostosis (DISH) is associated with cardiometabolic abnormalities, but its circulating immune-cell profile remains poorly characterized. This exploratory study examined immune-cell subsets and soluble inflammatory markers in relation to prevalent DISH. Method: Existing data from 526 participants in the 2021 Iwaki Health Promotion Project were analyzed using Firth-penalized logistic regression adjusted for age, sex, and visceral fat area. False-discovery-rate correction was applied jointly to eight immune-cell proportions and five inflammatory markers. Subsequent analyses characterized the CD16+CD56+ natural killer (NK)-cell association. Results: Forty-one participants had DISH. CD16+CD56+ NK-cell proportion was positively associated with DISH (OR per 10-percentage-point increase, 2.60; 95% CI, 1.81–3.73), whereas CD16−CD56− proportion was inversely associated (OR, 0.41; 95% CI, 0.29–0.58). Both associations remained significant after multiple-testing correction. Associations involving CD4+CD8− helper T cells and IL-6 were nominally significant but did not survive correction. Additional adjustment for smoking and alcohol use yielded a similar NK-cell estimate. Both NK-cell proportion and count were associated with DISH separately, but only the proportion remained significant when modeled together. Proportions differed across radiographic categories but were not associated with ossification burden among participants with DISH. Conclusions: DISH was associated with differences in circulating immune-cell proportions. These exploratory findings require independent confirmation and do not establish disease specificity, clinical biomarker utility, or a causal role in ossification.