BPIFB4 protein and monocytes phenotyping: a preclinical asset for marking the frailty condition

Abstract

Advanced age impacts on frequency and phenotype of immune cells as monocytes and macrophages. In this context, BPIFB4, a host defense protein with an immunomodulatory activity, has been found to be protective in healthy long living individuals in whom monocytes and macrophages have a favorable redistribution and phenotype. Thus, the aim of this study is to investigate the correlation between BPIFB4 levels in recruited frail subjects and both their frailty assessment/health status and monocytic profile. In this study, both a group of 40 frail individuals and 20 aged-matched healthy volunteers were recruited. Participants were subjected to standardized questionnaires to assess frailty risk, routine clinical examinations and blood test, monocytes extraction with next immunophenotypic FACS analysis. Overall, 70% of the frailty cohort has mild frailty, 25.5% has moderate frailty, and 5% has severe frailty. Compared to healthy controls, frail subjects show lower levels of circulating BPIFB4 that inversely correlate with the relative risk index for hypertension and cardiovascular disease. Flow cytometry results indicate total circulating monocyte frequency is reduced in frail subjects as compared to healthy controls. Considering monocytes’ subsets, CD14++CD16–classical monocytes and non-classical CD14+CD16++monocytes were significantly increased in frail people compared to old controls, whereas intermediate CD14++CD16+monocytes were reduced. Moreover, also the M2/M1 monocytic balance is altered in frailty condition compared to old volunteers. No relationship between BPIFB4 plasma levels and monocytes’subsets was found. Our findings highlight BPIFB4 protein has a potential prognostic value for marking the frailty condition.