An exploratory study on establishing reference intervals for circulating immune cells and an immune age prediction model in healthy young and middle-aged adults
Introduction: “Immune age” quantifies the immune system’s aging status, offering a new perspective for predicting disease risk and guiding health management. Although advanced technologies such as genomics have been used to develop immune age models, their high cost and complexity hinder their widespread application in healthy populations.
Objective: To establish reference intervals for circulating immune cells in healthy young and middle-aged adults, and to explore and construct an immune age prediction model using machine learning.
Methods: A study involving 124 healthy individuals measured 36 circulating immune cell parameters to establish population-based reference intervals. Six machine learning regression models were evaluated to identify the optimal model for predicting immune age. An open-source, visually enhanced web-based user interface was subsequently developed to improve model interpretability and provide a user-friendly experience.
Results: This study established preliminary reference intervals for 36 circulating immune cell parameters and identified significant age-related correlations in several of them. With increasing age, both the percentage and the absolute count of naive T cells declined significantly, whereas the percentage and absolute count of terminally differentiated T cells increased significantly. These changes are consistent with the established hallmarks of immunosenescence. Among six prediction models, the gradient boosting regressor demonstrated the best performance, achieving a mean absolute error of 6.295 years and a coefficient of determination of 0.491 on an independent test set. This indicates the model has preliminary predictive potential. Furthermore, this study exploratorily developed a web-based visualized tool for predicting immune age.
Conclusion: This study has preliminarily established reference intervals for circulating immune cells and exploratorily built an immune age prediction model for healthy young and middle-aged adults.
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