title: IgY antiporcine endothelial cell antibodies effectively block human antiporcine xenoantibody binding.
abstract: Avian IgY antibodies are structurally different from mammalian IgGs and do not fix mammalian complement components or bind human Fc receptors. As these antibody-mediated interactions are believed to play significant roles in both hyperacute rejection (HAR) and acute vascular xenograft rejection (AVXR), IgY antibodies to xenoantigen target epitopes may inhibit these rejection processes. In this report, we show that chicken IgY antibodies to alpha-Gal antigen epitopes and to other porcine aortic endothelial cell (PAEC) antigens block human xenoreactive natural antibody binding to both porcine and rat cardiac tissues and porcine kidney tissues. Chicken IgY antibodies blocked complement-mediated lysis of PAECs by human serum, and inhibited antibody-dependent cell-mediated lysis of PAECs by heat-inactivated human serum plus peripheral blood leukocytes. Binding of IgY to porcine endothelial cells did not affect cell morphology nor expression of E-selectin. These results suggest that avian IgYs could be of potential use in inhibiting pig-to-human xenograft rejection.
authors.affiliation: Department of Surgery, North-Western University Medical School, Chicago, IL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fryer
authors.forename: J
authors.initials: J
authors.lastname: Firca
authors.forename: J
authors.initials: J
authors.lastname: Leventhal
authors.forename: B
authors.initials: B
authors.lastname: Blondin
authors.forename: A
authors.initials: A
authors.lastname: Malcolm
authors.forename: D
authors.initials: D
authors.lastname: Ivancic
authors.forename: R
authors.initials: R
authors.lastname: Gandhi
authors.forename: A
authors.initials: A
authors.lastname: Shah
authors.forename: W
authors.initials: W
authors.lastname: Pao
authors.forename: M
authors.initials: M
authors.lastname: Abecassis
authors.forename: D
authors.initials: D
authors.lastname: Kaufman
authors.forename: F
authors.initials: F
authors.lastname: Stuart
authors.forename: B
authors.initials: B
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology* / Q000494:pharmacology; D015478:Antigens, Heterophile / Q000276:immunology*; D002645:Chickens; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology* / Q000494:pharmacology; D016377:Organ Transplantation; D051381:Rats; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
chemical_list: D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile; C016512:IgY; D007136:Immunoglobulins