Profiling natural serum antibodies of non-human primates with a carbohydrate antigen microarray

Engineering of a-Galactosyltransferase gene-knockout pigs circumvented hyperacute rejection of pig organs after xenotransplantation in non-human primates. Overcoming this hurdle revealed the importance of non-a-Gal carbohydrate antigens in the immunobiology of acute humoral xenograft rejection. This study analyzed serum from seven naïve cynomolgus monkeys (blood type O/B/AB = 3/2/2) for the intensity of natural IgM and IgG signals using carbohydrate antigen microarray, which included historically reported a-Gal and non-a-Gal carbohydrate antigens with various modifications. The median (range) of IgM and IgG signals were 12.71 (7.23-16.38) and 9.05 (7.23-15.90), respectively. The highest IgM and IgG signals with narrowest distribution were from mono- and disaccharides, followed by modified structures. Natural anti-a-Gal antibody signals were medium to high in IgM (11.2-15.9) and medium in IgG (8.5-11.6) spectra, and was highest with Lac core structure (Gala1-3Galß1-4Glc, iGb3) and lowest with LacNAc core structure (Gala1-3Galß1-4GlcNAc). Similar signal intensities (up to 15.8 in IgM and up to 11.8 in IgG) were observed for historically detected natural non-a-Gal antigens, which included Tn antigen, T antigen, GM2 glycolipid, and Sda antigen. The hierarchical clustering analysis revealed the presence of clusters of anti-A antibodies and was capable of distinguishing between the blood group B and AB non-human primates. The results presented here provide the most comprehensive evaluation of natural antibodies present in cynomolgus monkeys. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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