Background: With advancing age, the composition of leukocyte subpopulations in peripheral blood is known to change, but how this change differs between men and women and how it relates to frailty is poorly understood. Thus, our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether associations differed between men and women. Therefore, we performed in-depth immune cell phenotyping by enumerating subsets of T cells, B cells, NK cells, monocytes, and neutrophils in peripheral blood of 289 elderly people between 60-87 years of age. Associations between frailty and each immune cell subpopulation were tested separately in men and women and were adjusted for age and CMV serostatus. In addition, a random forest algorithm was used to predict a participant’s frailty score based on enumeration of immune cell subpopulations.
Results: Frailty was observed to be associated with numerical increases in neutrophils in men and in women. Furthermore, sex-specific associations were found with frailer men, but not women, showing higher numbers of non-classical monocytes and transitional B cells. In addition, frailer women, but not men, showed higher numbers of classical monocytes and lower numbers of NK-T cells. Interestingly, we did not detect an association between frailty and late differentiated memory T-cell subsets. Although the accuracy of the predictions of frailty from information on the immune subpopulations was low (10.7% explained variance in men and 10.5% in women), the prediction model confirmed our findings in the association study.
Conclusions: We here report on observed associations of frailty with elevated neutrophil numbers, but not with late stage memory T cell subsets. Furthermore, in-depth immune cellular profiling revealed sex specific associations of frailty with several immune subpopulations. We hope that our study will prompt further investigation into the immune mechanisms associated with the development of frailty in men and women.