Human serum albumin presents isoform variants with altered neonatal Fc Receptor interactions

Leblanc, Y., et al. Human serum albumin presents isoform variants with altered neonatal Fc Receptor interactions, Protein Science, Volume 28, Number 11, 1982-1992

Human serum albumin (HSA) is the most abundant protein in plasma and presents the particularity, with IgG, to have an extraordinary long serum half‐life conferred by its interaction with the neonatal Fc receptor (FcRn). If the impact of IgG post‐translational modifications (PTMs) on FcRn binding is well documented, it is far less reported for HSA despite numerous PTMs occurring on the protein in plasma. HSA is susceptible to numerous degradation reactions in plasma, because of aging, oxidative stress or liver and pancreas related pathologies. In the present study, we combined FcRn affinity chromatography and mass spectrometry to investigate the impact of HSA PTMs upon FcRn binding. This methodology presents the advantage to distinguish the effect of a single modification from a plasma HSA preparation made of a mixture of different isoforms. Cys34 oxidation, Lys525 glycation, and Leu585 C‐terminal truncation, which are modifications related to several pathological conditions, were demonstrated to act negatively on HSA‐FcRn interaction. The HSA‐FcRn binding alteration generated by these modifications is consistent with their vicinity with the interaction interface of the two proteins. Results were discussed regarding altered half‐life of HSA observed in several disease states and pave the way toward new understandings of the hypoalbuminemia pathogenesis.

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