High-mannose type N-glycans with core fucosylation and complex-type N-glycans with terminal neuraminic acid residues are unique to porcine islets

Objectives Islet transplantation is an emerging treatment option for type 1 diabetes but its application is limited by the shortage of human pancreas donors. Characterization of the N - and O -glycan surface antigens that vary between human and genetically engineered porcine islet donors could shed light on targets of antibody mediated rejection. Methods N - and O -glycans were isolated from human and adult porcine islets and analyzed using matrix-assisted laser-desorption time-of-flight mass spectrometry (MALDI-TOF-MS) and electrospray ionization mass spectrometry (ESI-MS/MS). Results A total of 57 porcine and 34 human N -glycans and 21 porcine and 14 human O -glycans were detected from cultured islets. Twenty-eight of which were detected only from porcine islets, which include novel xenoantigens such as high-mannose type N -glycans with core fucosylation and complex-type N -glycans with terminal neuraminic acid residues. Porcine islets have terminal N -glycolylneuraminic acid (NeuGc) residue in bi-antennary N -glycans and sialyl-Tn O -glycans. No galactose-α-1,3-galactose (α-Gal) or Sd a epitope were detected on any of the islets. Conclusions These results provide important insights into the potential antigenic differences of N - and O -glycan profiles between human and porcine islets. Glycan differences may identify novel gene targets for genetic engineering to generate superior porcine islet donors.