title: Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans.
abstract: BACKGROUND
  The availability of pigs homozygous for alpha1,3-galactosyltransferase gene-knockout (GT-KO) has enabled study of the incidence and cytotoxicity of primate antibodies directed to antigens other than Galalpha1,3Gal (Gal), termed non-Gal antigens.
  
  
  METHODS
  Sera from 27 healthy humans and 31 patients awaiting renal allotransplantation, who were either unsensitized [panel reactive antibodies (PRA) < 10%] or allosensitized (PRA > 70%), were tested by flow cytometry for binding of immunoglobulin M (IgM) and IgG to peripheral blood mononuclear cells (PBMC) from both wild-type (WT) and GT-KO pigs. Complement-dependent cytotoxicity to WT and GT-KO PBMC was also measured.
  
  
  RESULTS
  IgM and IgG from all 27 (100%) healthy human sera bound to WT PBMC, while 78% and 63% of these sera had IgM and IgG that bound to GT-KO PBMC, respectively. Mean binding to WT PBMC was significantly greater than GT-KO PBMC. Whereas 100% of sera were cytotoxic to WT PBMC, only 61% were cytotoxic to GT-KO PBMC, and the extent of lysis was significantly less. Neither mean binding of IgM and IgG nor cytotoxicity of unsensitized and allosensitized sera to WT and GT-KO PBMC was significantly different to that of healthy sera.
  
  
  CONCLUSIONS
  More than half of the healthy humans tested had cytotoxic antibodies to GT-KO PBMC, but allosensitized patients will be at no greater risk of rejecting a pig xenograft by a humoral mechanism.
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ezzelarab
authors.forename: Pleunie P M
authors.initials: PP
authors.lastname: Rood
authors.forename: Yih Jyh
authors.initials: YJ
authors.lastname: Lin
authors.forename: Jamie
authors.initials: J
authors.lastname: Busch
authors.forename: Zuhaib
authors.initials: Z
authors.lastname: Ibrahim
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: Adriana
authors.initials: A
authors.lastname: Zeevi
authors.forename: Michel
authors.initials: M
authors.lastname: Awwad
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
mesh_terms: D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004187:Disaccharides / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection; D006801:Humans; D007106:Immune Sera; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D013552:Swine / Q000235:genetics / Q000276:immunology*; D014181:Transplantation Immunology
chemical_list: D004187:Disaccharides; D007106:Immune Sera; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007519:Isoantigens; C055075:galactosyl-(1-3)galactose