Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man.
Human anti-pig antibodies were obtained by perfusing pig hearts (n = 4) and kidneys (n = 8) with human AB or O plasma followed by elution with 3 M NaSCN. The antibodies were screened against a panel of 132 synthetic carbohydrates conjugated to bovine serum albumin using an enzyme-linked immunoassay. An anti-immunoglobulin antibody was also used to detect immunoglobulin deposits on pig tissues. Four carbohydrate molecules with a terminal alpha-galactose residue bound all but one of the human anti-pig kidney antibodies and most of the anti-pig heart antibodies. These were: (i) alpha Gal(1-->3)beta Gal(1-->4)beta GlcNac (linear B type 2); (ii) alpha Gal(1-->3)beta Gal(1-->4)beta Glc (linear B type 6); (iii) alpha Gal(1-->3)beta Gal(B disaccharide); and (iv) alpha Gal(alpha-D-galactose). Immunoglobulin deposition was documented post-plasma perfusion in all pig hearts and particularly strongly in all pig kidneys. These results suggest that human anti-pig antibodies are mainly directed against alpha-galactosyl structures. Extracorporeal immunoadsorption of human plasma through columns of the specific synthetic carbohydrate(s) might lead to depletion of anti-pig antibodies and allow discordant xenografting in man. Alternatively, the infusion of the specific carbohydrate(s) for a period of several days might result in neutralization of the anti-pig antibodies and allow accommodation to take place.
Cooper
D K
DK
Oklahoma Transplantation Institute, Baptist Medical Center, Oklahoma City 73112.
Good
A H
AH
Koren
E
E
Oriol
R
R
Malcolm
A J
AJ
Ippolito
R M
RM
Neethling
F A
FA
Ye
Y
Y
Romano
E
E
Zuhdi
N
N
D000017:ABO Blood-Group System / Q000276:immunology; D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005690:Galactose / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007668:Kidney / Q000276:immunology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000276:immunology; D013045:Species Specificity; D013552:Swine / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
D000017:ABO Blood-Group System; D000910:Antibodies, Heterophile; D002241:Carbohydrates; D000939:Epitopes; D005690:Galactose