Carbohydrate antigen expression and anti-pig antibodies in New World capuchin monkeys: Relevance to studies of xenotransplantation

Academic Article

Abstract

  • © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Background: Old World non-human primates (OWNHPs) are used for preclinical pig-to-NHP studies. However, like pigs, OWNHPs express Neu5Gc, and therefore do not develop natural anti-Neu5Gc antibodies. New World NHPs (NWNHPs) have been reported not to express Neu5Gc. We investigated the potential of NWNHPs in xenotransplantation research. Methods: We investigated expression of Gal, Neu5Gc, and Sdaantigens on RBCs and PBMCs from humans, selected OWNHPs, and capuchin monkeys (a NWNHP). Serum anti-Gal and anti-Neu5Gc IgM and IgG levels were measured by ELISA. Binding of primate serum IgM and IgG to pig RBCs was measured by flow cytometry. Results: (a) Neither humans, OWNHPs, or capuchin monkeys expressed Gal on their RBCs, but capuchins expressed Gal on PBMCs. Humans and capuchins did not express Neu5Gc on either RBCs or PBMCs, but OWNHPs expressed Neu5Gc on both cells. Sdawas not expressed on any RBCs or PBMCs. (b) By ELISA, human and OWNHP, but not capuchin, sera showed IgM and IgG binding to Gal. Human and capuchin, but not OWNHP, sera demonstrated some binding to Neu5Gc. (c) Anti-Sda IgM/IgG antibodies were detected in OWNHP sera. Knockout of Sda on pig RBCs did not significantly reduce human and capuchin antibody binding. Conclusion: Capuchin monkeys could be surrogates for humans in experiments using RBCs, islets, neuronal cells, etc, from triple-knockout pigs (but may be too small to be used as recipients of pig organ grafts).
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    Author List

  • Li Q; Shaikh S; Iwase H; Long C; Lee W; Zhang Z; Wang Y; Ayares D; Cooper DKC; Hara H
  • Volume

  • 26
  • Issue

  • 3