Mass spectrometry-based analysis on the impact of iron status and whole blood donation on the global plasma proteome

Blood donation is generally considered to be safe, however to ensure blood donor health it is important to monitor the impact of a whole blood donation. Study design and methods Here, we used quantitative mass spectrometry to assess the global plasma proteomic impact of longitudinal whole blood donation in 5 new and 4 regular donors over a period of 180 days as well as the effect on iron status, by selecting 78 donors based on high levels of ferritin and hemoglobin. The majority of plasma proteins were stable between whole blood donors and demonstrated a low coefficient of variation, irrespective to iron status or donors status (new or regular). Longitudinal analysis showed limited differences between the plasma proteomes of regular and new upon a whole blood donation, apart from a consistent and significant short-term decrease in fibronectin. Plasma protein levels measured with MS highly correlated with blood count and lipid parameters, validating our MS-approach. Based on protein co-expression, we observed protein complexes of diverse biological processes, platelet and neutrophil signatures, complement and immune responses with a highly correlating cluster of IGHM, IGJ and CD5L. We showed higher inter- than intra-individual variation, most notably of immunoglobulins and allelic variants for alpha-1 antitrypsin. Overall, this study shows that whole blood donation has limited impact for both new and regular donors apart from short-term decreases in fibronectin and that varying iron statuses do not affect the global plasma proteome. We showed that individual specific signatures were reflected on the plasma proteome as well as detection of allelic variants