A study of the xenoantigenicity of adult pig islets cells

• Published in: Xenotransplantation (Københaven) Vol. 11; no. 3; pp. 237 - 246
• Main Authors: Komoda, Hiroshi, Miyagawa, Shuji, Kubo, Tomoko, Kitano, Etsuko, Kitamura, Hajime, Omori, Takeshi, Ito, Toshinori, Matsuda, Hikaru, Shirakura, Ryota
• Format: Journal Article
• Language: English
• Published: Oxford, UK Munksgaard International Publishers 01.05.2004
• Subjects: ABO Blood-Group System; Animals; Antigens, Heterophile - immunology; Cell Separation; complement; Disaccharides - immunology; Galactosyltransferases - analysis; Hanganutziu-Deicher antigen; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - enzymology; Islets of Langerhans - immunology; N-linked sugar; Neuraminidase - pharmacology; non-α Gal antigen; pig islets; Swine; Tunicamycin - pharmacology
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1111/j.1399-3089.2004.00121.x

:  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.