Measurement of erythrocyte membrane mannoses to assess splenic function

Area of Science:

• Hematology
• Immunology
• Glycobiology

Background:

• Red blood cells (RBCs) shed membrane components in the spleen during aging.
• Oxidative stress in sickle cell disease and Plasmodium falciparum infection causes protein aggregation with high-mannose glycans (HMGs).
• Mannose-binding lectins, like the mannose receptor (CD206), recognize HMGs on phagocytic cells in the spleen, mediating extravascular hemolysis.

Purpose of the Study:

• To investigate the role of HMGs in RBC removal in healthy individuals.
• To assess if HMGs on RBCs can serve as a marker for splenic reticuloendothelial function.
• To evaluate HMG levels in patients with potential functional hyposplenism.

Main Methods:

• Assessed surface HMG expression on RBCs from splenectomized patients.
• Performed glycomic analysis using mass spectrometry to identify HMG structures.
• Correlated HMG levels with manual pit counts.
• Measured HMG levels on RBCs from patients with functional hyposplenism.

Main Results:

• Splenectomized patients showed high levels of HMGs as large membrane aggregates.
• Mass spectrometry identified Man5-9GlcNAc2 structures as the predominant HMGs.
• HMG levels strongly correlated with manual pit counts (r = 0.75-0.85).
• Patients with functional hyposplenism exhibited elevated HMG levels.

Conclusions:

• HMGs on RBCs are involved in splenic clearance mechanisms, even in healthy individuals.
• HMG levels on RBCs may serve as a valuable indicator of splenic reticuloendothelial function.
• Elevated HMGs in patients with hyposplenism could signify an increased risk of complications.