P1PK blood group antigens in birds: implications for veterinary blood transfusion, human and pet health.

Abstract

BACKGROUND: The P1PK blood group system in humans, composed of three glycosphingolipid antigens, plays a significant role in transfusion medicine. These antigens are synthesized by the enzyme α1,4-galactosyltransferase, encoded by the A4GALT gene, and also act as receptors for Shiga toxins, which are key virulence factors produced by pathogenic strains of Escherichia coli. Birds are known to be resistant to the effects of Shiga toxins, yet the molecular basis of this resistance has remained unclear. This study aimed to investigate the presence, expression, and functional role of P1PK antigens in birds, particularly in relation to their exposure to human-associated bacteria. RESULTS: Birds residing in urban environments, such as pigeons (Columba livia) and crows (Corvus cornix), express higher levels of Shiga toxin receptors on their red blood cells. These levels are higher compared to species living in more isolated areas, such as woodcocks (Scolopax rusticola). This pattern may suggest an evolutionary adaptation to human environments. We analyzed RBC glycan expression in 52 birds representing 10 species using flow cytometry, mass spectrometry, and HPTLC to assess interspecies variation in P1PK-related antigens. We propose that the increased expression of these antigens in urban birds functions as a decoy mechanism, reducing the toxicity of Shiga toxins by sequestering them before they can cause cellular damage. The glycomic analysis identified novel glycosphingolipids and glycoproteins with terminal galactose residues that are specifically recognized by the B subunit of Shiga toxin. In addition, we found that a cellular protein, RAB11FIP5, may influence the intracellular trafficking of Shiga toxins, adding another layer of protection in birds. CONCLUSIONS: Our data suggests that certain birds, particularly those residing in human-influenced environments, possess mechanisms that enable them to partially tolerate or neutralize Shiga toxins. These findings provide a basis for comparative studies of avian red blood cell glycan biology and offer valuable context for future research in veterinary transfusion science and immunology.