title: Incidence and cytotoxicity of antibodies in cynomolgus monkeys directed to nonGal antigens, and their relevance for experimental models.
abstract: The recent availability of pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) has enabled the study of incidence and cytotoxicity of antibodies of cynomolgus monkeys directed to antigens other than Galalpha1,3Gal (Gal), termed nonGal antigens. To this aim, sera from 21 cynomolgus monkeys were tested by flow cytometry for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from wild-type (WT) and GT-KO pigs. The sera were also tested for complement-dependent cytotoxicity to WT and GT-KO PBMC. Anti-WT IgM and IgG were found in 100% and 95%, respectively, and anti-GT-KO IgM and IgG in 76% and 66%, respectively, in the sera of the monkeys tested (P < 0.01). Whereas 100% of sera were cytotoxic to WT PBMC, only 76% were cytotoxic to GT-KO PBMC, and the level of cytotoxicity was significantly less (P < 0.01). Although the incidence and cytotoxicity of antibodies in monkey sera to GT-KO pig PBMC are significantly less than to WT PBMC, approximately three-quarters of the monkeys tested had cytotoxic antibodies to GT-KO PBMC. This incidence of cytotoxicity is significantly higher than that found in baboons and humans, suggesting the baboon may be an easier and possibly more suitable model to study antibody-mediated rejection of transplanted GT-KO pig organs and cells.
authors.affiliation: The Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
authors.forename: Pleunie P M
authors.initials: PP
authors.lastname: Rood
authors.forename: Pleunic P M
authors.initials: PP
authors.lastname: Rood
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Busch
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Zhu
authors.forename: Suyapa
authors.initials: S
authors.lastname: Ball
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.forename: Michel
authors.initials: M
authors.lastname: Awwad
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood*; D003165:Complement System Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology; D008252:Macaca fascicularis / Q000276:immunology*; D013552:Swine; D014312:Trisaccharides / Q000276:immunology*
chemical_list: D000910:Antibodies, Heterophile; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D003165:Complement System Proteins; D005700:Galactosyltransferases