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A study of the xenoantigenicity of adult pig islets cells
Author(s) -
Komoda Hiroshi,
Miyagawa Shuji,
Kubo Tomoko,
Kitano Etsuko,
Kitamura Hajime,
Omori Takeshi,
Ito Toshinori,
Matsuda Hikaru,
Shirakura Ryota
Publication year - 2004
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2004.00121.x
Subject(s) - antigenicity , islet , xenotransplantation , antibody , neuraminidase , antigen , biology , epitope , microbiology and biotechnology , pancreatic islets , chemistry , endocrinology , medicine , biochemistry , immunology , transplantation , insulin , enzyme
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 Gal α 1‐3Gal β 1‐4GlcNAc‐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 α 1,3 galactosyltransferase ( α 1,3GT) 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 α 1,3GT 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.