Anti-GAL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation

Oktavijan P. Minanov, Silviu Itescu, Francisca A. Neethling, Adam S. Morgenthau, Pawel Kwiatkowski, D. K.C. Cooper, Robert E. Michler

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

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 α-1, 3- galactosyl (α 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-α Gal activity with an ELISA using BSA-conjugated α Gal residues as target. To evaluate the significance of the anti-α 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-α Gal IgG antibodies at titers of 1:80 or greater. None of the samples had anti-α Gal IgM. In newborn baboons, 1 of 5 sera had anti-α Gal IgG antibodies at titers greater than 1:80 and none of these samples had anti-α Gal IgM. Xenografts survived for an average of 3.6 days, even in the baboon with high anti-α 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-α Gal response with cytotoxicity against PK-15 cells. These results show that anti-α Gal IgM is absent in newborn human and baboon sera, allowing pig grafts to avoid HAR. However, the presence of anti-α Gal IgG may be associated with mononuclear cell infiltration of the xenograft and its subsequent rejection.

Original languageEnglish (US)
Pages (from-to)182-186
Number of pages5
JournalTransplantation
Volume63
Issue number2
DOIs
StatePublished - Jan 27 1997
Externally publishedYes

ASJC Scopus subject areas

  • Transplantation

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    Minanov, O. P., Itescu, S., Neethling, F. A., Morgenthau, A. S., Kwiatkowski, P., Cooper, D. K. C., & Michler, R. E. (1997). Anti-GAL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation. Transplantation, 63(2), 182-186. https://doi.org/10.1097/00007890-199701270-00002