Measurement of erythrocyte membrane mannoses to assess splenic function

Huan Cao* (Corresponding Author), Abhinav Mathur, Charlotte Robertson, Aristotelis Antonopoulos, Sadie Henderson, Louis-Pierre Girard, Jin Hien Wong, Adam Davie, Sonja Wright, John N. Brewin, David C. Rees, Anne Dell, Stuart M Haslam, Mark Vickers

*Corresponding author for this work

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Abstract

Red blood cells (RBCs) lose plasma membrane in the spleen as they age, but the cells and molecules involved are yet to be identified. Sickle cell disease and infection by Plasmodium falciparum cause oxidative stress that induces aggregates of cross-linked proteins with N-linked high-mannose glycans (HMGs). These glycans can be recognised by mannose-binding lectins, including the mannose receptor (CD206), expressed on macrophages and specialised phagocytic endothelial cells in the spleen to mediate the extravascular haemolysis characteristic of these diseases. We postulated this system might also mediate removal of molecules and membrane in healthy individuals. Surface expression of HMGs on RBCs from patients who had previously undergone splenectomy was therefore assessed: high levels were indeed observable as large membrane aggregates. Glycomic analysis by mass spectrometry identified a mixture of Man5-9GlcNAc2 structures. HMG levels correlated well with manual pit counts (r = 0.75–0.85). To assess further whether HMGs might act as a splenic reticuloendothelial function test, we measured levels on RBCs from patients with potential functional hyposplenism, some of whom exhibited high levels that may indicate risk of complications.
Original languageEnglish
JournalBritish Journal of Haematology
Early online date12 Apr 2022
DOIs
Publication statusE-pub ahead of print - 12 Apr 2022

Keywords

  • glycosylation
  • membrane editing
  • oxidative damage
  • red blood cells
  • splenectomy

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