Proteomic analyses of human plasma: Venus versus Mars

Abstract

BACKGROUND: Plasma is vital for the resuscitation of injured patients and to restore necessary procoagulants, especially Factors (F)II, FV, FVII, FX, and FXIII; however, female plasma has been implicated in the majority of transfusion‐related acute lung injury (TRALI) cases and male‐only plasma transfusion regimens have significantly decreased the incidence of TRALI. Little is known about the human plasma proteome, and no comparisons have been made between male and female plasma; therefore, we hypothesize that there are significant differences between plasma from male and female donors. STUDY DESIGN AND METHODS: Five units of fresh‐frozen plasma each were collected from nulliparous female donors and male donors, and the proteome was analyzed by depleting the 14 most common proteins by immunoaffinity columns followed by protein separation by one dimension gel electrophoresis, tryptic digestion of the proteins, analysis of the peptides by liquid chromatography–tandem mass spectrometry, and identification employing human protein sequence databases. RESULTS: Female plasma versus male plasma contained pregnancy zone protein (419‐ to 580‐fold), FV (twofold), α₁‐antitrypsin (twofold), β₂‐microglobulin (twofold), and Complement Factors H and C4B (1.5‐ to 2‐fold) at significantly higher concentrations than males and males contained significant increases in Fc‐binding protein (twofold), protein Z–dependent protease inhibitor (twofold), phosphatidylinositol glycan–specific phospholipase (fourfold), protein S‐100 (threefold), and transgelin‐2 (14‐fold) versus females (p < 0.005). The increases in FV, α₁‐antitrypsin, and β₂‐microglobulin were confirmed by an activity assay or immunoblots. CONCLUSION: We conclude that there are proteomic differences between male and female plasma, which could be exploited to improve clinical outcomes in transfused patients.