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Xenotransplantation. 2004 May;11(3):237-46.

A study of the xenoantigenicity of adult pig islets cells.

Author information

1
Division of Organ Transplantation, Department of Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.

Abstract

BACKGROUND:

The pig pancreas is considered to be the most suitable source of islets for xenotransplantation into patients with type I diabetes. The purpose of this study was to assess the antigenicity of pig islets, including the Galalpha1-3Galbeta1-4GlcNAc-R (the alpha-Gal) and Hanganutziu-Deicher (H-D) antigens, and the pathway involved in human complement activation.

METHODS:

The expression of alpha-Gal on islets from adult pigs was investigated by immunohistochemical staining and flowcytometric analysis. The alpha1,3 galactosyltransferase (alpha1,3GT) activity of islets was determined by high-performance liquid chromatography. Antigenicity to human natural antibodies, including the H-D antigen of pig islets was next examined by treatment of pig islets with tunicamycin, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and/or neuraminidase. In addition, complement-mediated islets lysis was examined using factor D-deficient and C1-deficient sera.

RESULTS:

Adult pig islets expressed negligible amounts of alpha-Gal epitope, and alpha1,3GT activity was also undetectable. However, human natural antibodies, immunoglobulin G and M, and the anti H-D antibody react to the adult islet. Treatment of pig islets with tunicamycin, but not PDMP, led to a drastic reduction in antigenicity to human serum, indicating the importance of N-linked sugars on the islets. Neuraminidase treatment indicated the presence of, not only the H-D antigen, but also other sialic acid antigens that reacted with the human natural antibody. The complement deposition of C4, C3 and factor B on islets was demonstrated. The alternative pathway-mediated pig islet killing accounted for approximately 30% of that by the total complement pathway.

CONCLUSION:

The origin of antigenicity of pig islets is mainly N-linked sugars including sialic acid antigens, but not the alpha-Gal, and pig islets can be injured by both the classical and the alternative complement pathway in human serum.

[Indexed for MEDLINE]

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