Anti-GaL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation.
We have previously demonstrated that hyperacute rejection does not occur in a pig-to-newborn baboon heart transplant model, presumably because of low levels of cytotoxic antipig antibodies present in the serum of newborn baboons. Cytotoxic antipig antibodies are primarily directed to alpha-1,3-galactosyl (alpha Gal) residues on endothelial cell surface structures Twenty-one full-term humans and 5 full-term baboons were tested for complement mediated lysis (CML) of pig kidney (PK-15) cells and anti-alpha Gal activity with an ELISA using BSA-conjugated alpha Gal residues as target. To evaluate the significance of the anti-alpha Gal titers in vivo 5 newborn baboons underwent heterotopic pig cardiac xenotransplantation. Six of 21 human samples and 1 of 5 baboon samples demonstrated significant cytotoxicity to PK-15 cells. Twelve of 21 newborn humans had anti-alpha Gal IgG antibodies at titers of 1:80 or greater. None of the samples had anti-alpha Gal IgM. In newborn baboons, 1 of 5 sera had anti-alpha Gal IgG antibodies at titers greater than 1:80 and none of these samples had anti-alpha Gal IgM. Xenografts survived for an average of 3.6 days, even in the baboon with high anti-alpha Gal IgG titers. Analysis of the explanted grafts showed minimal evidence of complement-mediated hyperacute rejection (HAR), but prominent mononuclear cell infiltrates. In serum tested posttransplant there was an induced anti-alpha Gal response with cytotoxicity against PK-15 cells. These results show that anti-alpha Gal IgM is absent in newborn human and baboon sera, allowing pig grafts to avoid HAR. However, the presence of anti-alpha Gal IgG may be associated with mononuclear cell infiltration of the xenograft and its subsequent rejection.
Minanov
O P
OP
Division of Cardiothoracic Surgery, Columbia-Presbyterian Medical Center, New York, NY 10032, USA.
Itescu
S
S
Neethling
F A
FA
Morgenthau
A S
AS
Kwiatkowski
P
P
Cooper
D K
DK
Michler
R E
RE
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005312:Fetal Blood; D005697:Galactosides / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007231:Infant, Newborn; D007668:Kidney; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology; D016042:Transplantation, Heterotopic
D005697:Galactosides; D007074:Immunoglobulin G