Forssman penta- and tetraglycosylceramide are xenoantigens of ostrich kidney and liver

Abstract

The heterophile antigens Galalpha1-->3Gal and N-glycolylneuraminic acid are the major obstacle to grafting mammal organs, especially from pig, to man. Lack of expression of these common xenoantigens by birds has raised interest in ostrich as a potential organ donor for xenotransplantation. Glycosphingolipids of ostrich liver and kidney were investigated for their carbohydrate determinants. Both organs were found similar in their glycolipid composition with three major species, mono-, di-, and pentaglycosylceramide. The pentaglycosylceramide was characterized as the Forssman antigen. In both organs, the ceramide portion was highly hydroxylated with prevalence of alpha-hydroxylated fatty acids, C18 phytosphingosine in kidney and C18 sphingosine in liver Forssman glycolipid. These data indicate that hydroxylation of kidney glycosphingolipids, which is found in mammals, has been maintained since the divergence of birds from other vertebrates. Characterization of a minor glycolipid as a Forssman tetraglycosylceramide built on the galabiosylceramide core indicates that the Forssman tetraglycosylceramide also exists in vivo. Its precursors, galactosyl- and galabiosylceramide, were characterized in kidney and liver. The Forssman antigen is the third heterophile antigen against which man raises natural antibodies. Its localization in the vascular endothelium and connective tissue makes ostrich an unpromising organ or cell donor for xenotransplantation to man.

2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length

“…The presence of 2-hydroxy-CER is limited to specific tissues, such as brain, skin, and kidney (6,16,32). This distribution pattern coincides with the tissue-specific expression of FA2H mRNA (7).…”

“…In addition, phytosphingosine (phyto-Sph), containing a hydroxyl group at the C-4 position, is detectable in certain tissues, including skin, small intestine, and kidney (14)(15)(16); skin also contains a unique LCB, 6-hydroxy-sphingosine (6-hydroxy-Sph) (17). Thus, due to the diverse species of LCBs and FAs available, skin contains unusually varied CER types.…”

Anticarbohydrate Antibody Repertoires in Patients Transplanted with Fetal Pig Islets Revealed by Glycan Arrays

“…(12,13), sulfatide (14), the pk antigen (Gala4Galb4Glcb1Cer) (15,16) and other a-Gal-terminated structures (17). Abs to the Forssman antigen has been detected in human serum (18), while the presence of the Forssman glycolipid (GalNAca3GalNAcb3Gala4Galb4Glcb1Cer) has not been unequivocally shown in the pig (19,20 (23). A significant rise in the anti-a-Gal antibody titer was observed peaking at day 30-50 (16,24,25), but also non-Gal specificities were detected in some patients (26).…”

Anti‐N‐glycolylneuraminic acid antibodies identified in healthy human serum

“…In fact, anti‐HD Ab was first identified in people who had been previously exposed to animal sera. As anti‐HD Ab has so far not been identified in normal human sera, HD‐antigen on porcine cells or tissues has not been considered to be directly involved in hyperacute rejection in pig‐to‐human transplantation [13].…”