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

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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

Fingerprint

Heterologous Transplantation
Papio
Swine
Antibodies
Serum
Transplants
Heterografts
anti-IgG
Endothelial Cells
Enzyme-Linked Immunosorbent Assay
Kidney

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

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

Anti-GAL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation. / Minanov, Oktavijan P.; Itescu, Silviu; Neethling, Francisca A.; Morgenthau, Adam S.; Kwiatkowski, Pawel; Cooper, D. K C; Michler, Robert E.

In: Transplantation, Vol. 63, No. 2, 27.01.1997, p. 182-186.

Research output: Contribution to journalArticle

Minanov, OP, Itescu, S, Neethling, FA, Morgenthau, AS, Kwiatkowski, P, Cooper, DKC & Michler, RE 1997, 'Anti-GAL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation', Transplantation, vol. 63, no. 2, pp. 182-186. https://doi.org/10.1097/00007890-199701270-00002
Minanov OP, Itescu S, Neethling FA, Morgenthau AS, Kwiatkowski P, Cooper DKC et al. Anti-GAL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation. Transplantation. 1997 Jan 27;63(2):182-186. https://doi.org/10.1097/00007890-199701270-00002
Minanov, Oktavijan P. ; Itescu, Silviu ; Neethling, Francisca A. ; Morgenthau, Adam S. ; Kwiatkowski, Pawel ; Cooper, D. K C ; Michler, Robert E. / Anti-GAL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation. In: Transplantation. 1997 ; Vol. 63, No. 2. pp. 182-186.
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