Glycolipid studies in small intestine and pancreas of alpha 1,3-galactosyltransferase knockout miniature swine: alpha 1,3GALT-KO animals lack alpha GAL antigens and contain novel blood group H compounds

作者：Diswall M^*; Angstroem J; Schuurman H J; Dor F J M F; Rydberg L; Breimer M E

来源：Transplantation Proceedings, 2008, 40(2): 543-546.

DOI：10.1016/j.transproceed.2008.01.032

Background. To avoid hyperacute rejection of xeno-organs, alpha 1,3-galactosyltransferase knock-out (GalT-KO) pigs have been produced. However, Gal alpha 1,3Gal (Gal) determinant elimination may expose cryptic carbohydrate antigens and/or generate new antigens that might interfere with the human immune response.
Methods. Glycolipids isolated from small intestine and pancreas of two GalT-KO and one wild-type (WT) pig were tested for immune reactivity with antibodies on thin-layer chromatograms after separation by high-performance liquid chromatography, and selected fractions were analysed by proton NMR spectroscopy.
Results. Immunostaining using purified human anti-Gal Abs revealed that tissues from WT animals express large amounts of Gal-antigens whereas GalT-KO tissues lacked these antigens. Proton NMR spectroscopy on small intestine fractions revealed both linear and branched nona- and decaglycosylceramides, respectively, with terminal Gal-epitopes. In corresponding GalT-KO fractions, Gal-epitopes seemed to be replaced by terminal alpha 1,2fucoses. Two novel branched blood group H compounds was found in the GalT-KO intestine.
Conclusions. The structural complexity of alpha Gal-terminating antigens in the WT organs is very high. Knockout of alpha 1,3GalT by gene-targeting results in elimination of Gal-determinants. In addition structurally novel alpha 1,2fucose-terminated blood group H compounds were identified in the GalT-KO tissue. These compounds are not expected to be recognized by the human immune system.

• 出版日期2008-3