Anti-pig antibody levels in naïve baboons and cynomolgus monkeys

• Published in: Xenotransplantation (Københaven) 2002-03, Vol.9 (2), p.135-147
• Main Authors: Holmes, Beverly J., Richards, Andrew C., Awwad, Michel, Copeman, Laura S., Mclaughlin, Megan L., Cozzi, Emanuele, Schuurman, Henk-Jan, Davies, Hugh F. S.
• Format: Article
• Language: English
• Subjects: Animals; anti-Gal antibody; anti-pig antibody levels; antilymphocyte antibody; baboon; cynomolgus monkey; Disaccharides - chemistry; Disaccharides - immunology; Galα1-3Gal antigen; Graft Rejection - immunology; Heart Transplantation; hemolytic antibody; hyperacute rejection; Isoantibodies - blood; Isoantibodies - immunology; Macaca fascicularis; Papio; Swine; Transplantation, Heterologous
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1034/j.1399-3089.2002.1o056.x

Anti‐pig antibodies (APA) were analysed in serum from 28 naïve wild‐caught baboons (originating from Kenya) and 31 naïve captive‐bred cynomolgus monkeys (13 from the Philippines and 18 from Mauritius), using a haemolytic assay with pig erythrocytes (APA), flow cytometry on the porcine lymphoma T‐cell cell line L35, and enzyme linked immunosorbent assay (ELISA) using α‐Gal type II and type VI antigen. This was extended in baboon samples by the evaluation in two laboratories (Imutran, Cambridge, UK and Immerge, Boston, USA), and by antibody absorption using either immobilized α‐Gal type II or α‐Gal type VI. Anti‐porcine antibodies were demonstrated in all assays with substantial variability within and between the three non‐human primate groups. Immunoglobulin (Ig)M antibody levels tended to be similar to or higher than those in a pooled normal human standard serum while IgG levels tended to be lower. Highest antibody levels were recorded in Mauritius cynomolgus monkeys. There were statistically significant correlations between assays for IgM or IgG class anti‐Gal antibodies using either α‐Gal type II or α‐Gal type VI as antigen, both for different assays and two laboratories involved. Also, significant correlations were observed between the anti‐Gal and L35 binding assays. Baboon sera before and after absorption to immobilized α‐Gal type II or type VI were analysed for anti‐Gal type VI or type II antibody: levels were almost undetectable indicating that most anti‐Gal antibodies react to epitopes shared between α‐Gal type II and type VI oligosaccharides. Finally, the relation between APA and outcome of porcine heart xenotransplantation in cynomolgus monkeys and baboons showed no apparent relation between pre‐transplant APA levels and the occurrence of hyperacute rejection (HAR) when compared with non‐immunological cause of organ/recipient dysfunction or acute humoral xenograft rejection during the first 4 days post‐transplantation or survival exceeding 4 days post‐transplantation.