A lectin microarray study of glycoantigens in neonatal porcine islet-like cell clusters

Maeda, Akira; Ueno, Takayoshi; Nakatsu, Shino; Wang, Dandan; Usui, Noriaki; Takeishi, Shunsaku; Okitsu, Teru; Goto, Masafumi; Nagashima, Hiroshi; Miyagawa, Shuji

doi:10.1016/j.jss.2012.12.037

Cited by 10 publications

(5 citation statements)

References 22 publications

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“…However, the ratio of Neu5Gc/Neu5Ac varies widely among porcine tissues and is dependent on CMAH activity in the tissue . In the context of xenotransplantation, Neu5Gc has been described on the vascular endothelium‐cell surface of pigs, including the kidney, liver, heart, and pancreas , in neonatal porcine islet‐like cell clusters and, in contrast to Gal, also in adult pig pancreatic islets . All layers of the pig cornea also strongly express Neu5Gc .…”

Section: Neu5gc In Live or Devitalized Xenografts And In Human Tissuementioning

confidence: 99%

Potential deleterious role of anti‐Neu5Gc antibodies in xenotransplantation

Salama

Evanno

Harb

et al. 2014

Xenotransplantation

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Human beings do not synthesize the glycolyl form of the sialic acid (Neu5Gc) and only express the acetylated form of the sugar, whereas a diet-based intake of Neu5Gc provokes a natural immunization and production of anti-Neu5Gc antibodies in human serum. However, Neu5Gc is expressed on mammal glycoproteins and glycolipids in most organs and cells. We review here the relevance of Neu5Gc and anti-Neu5Gc antibodies in the context of xenotransplantation and the use of animal-derived molecules and products, as well as the possible consequences of a long-term exposure to anti-Neu5Gc antibodies in recipients of xenografts. In addition, the importance of an accurate estimation of the anti-Neu5Gc response following xenotransplantation and the future contribution of knockout animals mimicking the human situation are also assessed.

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Section: Neu5gc In Live or Devitalized Xenografts And In Human Tissuementioning

confidence: 99%

Potential deleterious role of anti‐Neu5Gc antibodies in xenotransplantation

Salama

Evanno

Harb

et al. 2014

Xenotransplantation

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“…In wild-type (WT) pigs, the Neu5Gc/Neu5Ac ratio varies in tissues depending on the CMAH activity intensity, but Neu5Gc is thus present in pig heart, kidney, spleen, lung, cornea and liver (42)(43)(44)(45). The antigenicity of NPCCs (46) and adult porcine islets (47)(48)(49) was also linked to the expression of Neu5Gc epitopes and the presence of Gal antigen (50). Neu5Gc is also largely detected in erythrocytes (51).…”

Section: Neu5gc a Major Non-gal Glycan Xenoantigenmentioning

confidence: 99%

The Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation

et al. 2020

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Seventy to ninety percentage of preformed xenoreactive antibodies in human serum bind to the galactose-α(1,3)-galactose Gal epitope, and the creation of Gal knockout (KO) pigs has eliminated hyperacute rejection as a barrier to xenotransplantation. Now other glycan antigens are barriers to move ahead with xenotransplantation, and the N-glycolyl neuraminic acid, Neu5Gc (or Hanganutziu-Deicher antigen), is also a major pig xenoantigen. Humans have anti-Neu5Gc antibodies. Several data indicate a strong immunogenicity of Neu5Gc in humans that may contribute to an important part in antibody-dependent injury to pig xenografts. Pig islets express Neu5Gc, which reacted with diet-derived human antibodies and mice deleted for Neu5Gc reject pancreatic islets from wild-type counterpart. However, Neu5Gc positive heart were not rejected in Neu5Gc KO mice indicating that the role of Neu5Gc-specific antibodies has to be nuanced and depend of the graft situation parameters (organ/tissue, recipient, implication of other glycan antigens). Recently generated Gal/Neu5Gc KO pigs eliminate the expression of Gal and Neu5Gc, and improve the crossmatch of humans with the pig. This review summarizes the current and recent experimental and (pre)clinical data on the Neu5Gc immunogenicity and emphasize of the potential impact of anti-Neu5Gc antibodies in limiting xenotransplantation in humans.

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“…Is there any published evidence suggesting that this age is optimal? Most studies of pig NICC transplantation into mice have used donors of 1 to 7 days of age .…”

Section: Is There An Optimal Age For Isolation Of Iccs From Neonatal mentioning

confidence: 99%