A study of the xenoantigenicity of adult pig islets cells.

:  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 Galα1-3Galβ1-4GlcNAc-R (the α-Gal) and Hanganutziu-Deicher (H-D) antigens, and the pathway involved in human complement activation. Methods:  The expression of α-Gal on islets from adult pigs was investigated by immunohistochemical staining and flowcytometric analysis. The α1,3 galactosyltransferase (α1,3GT) 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 α-Gal epitope, and α1,3GT 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 α-Gal, and pig islets can be injured by both the classical and the alternative complement pathway in human serum.