Anti-gal antibodies in humans and 1, 3α-galactosyltransferase knock-out mice

Tsu Rong Chiang, Laurent Fanget, Richard Gregory, Yong Tang, Denis Luc Ardiet, Lan Gao, Carol Meschter, Alan P. Kozikowski, Roland Buelow, Wim M.J. Vuist

Research output: Contribution to journalArticle

Abstract

Background. Due to the absence of αGAL epitopes, humans and galactosyltransferase knock-out (GALT/KO) mice express high levels of anti- Gal antibodies. We describe the properties of mouse anti-GAL antibodies. Methods. Anti-GAL IgG antibodies were quantified by affinity purification. Antibody affinities and avidities were determined in direct binding and competition assays. Antibody-mediated rejection was investigated using hyperimmunized GALT/KO mice as recipients of GAL+ heart allografts. Results. In young GALT/KO mice the levels of anti-GAL antibodies were low. Immunization of GALT/KO mice resulted in increased anti-GAL antibody expression. In mouse serum 0.6% of IgG was specific for αGAL compared to 0.5% in human serum. The avidity of purified mouse and human anti-GAL IgG was 30 and 6 nM, the affinity 15 and 50 μM, respectively. The isotype distribution in mouse and human anti-GAL IgG appeared to be similar to the isotype distribution in normal sera. The affinity of mouse and human antiGAL IgM was 150 and 750 μM, respectively. Immunized GALT/KO recipients of GAL+ heart transplants rejected their grafts within 2 hr although nonimmunized GALT/KO mice retained their grafts for up to 6 days. Immunohistological examination of the rejected GAL+ hearts revealed massive deposition of IgM and IgG on endothelial cells of the graft with a concomitant deposition of complement. Conclusions. Our studies demonstrate that anti-GAL antibodies from immunized GALT/KO mice bind αGAL with an avidity/affinity similar to human anti-GAL antibodies and are able to induce hyperacute rejection of GAL+ heart allografts.

Original languageEnglish (US)
Pages (from-to)2593-2600
Number of pages8
JournalTransplantation
Volume69
Issue number12
DOIs
StatePublished - Jun 27 2000

ASJC Scopus subject areas

  • Transplantation

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    Chiang, T. R., Fanget, L., Gregory, R., Tang, Y., Ardiet, D. L., Gao, L., Meschter, C., Kozikowski, A. P., Buelow, R., & Vuist, W. M. J. (2000). Anti-gal antibodies in humans and 1, 3α-galactosyltransferase knock-out mice. Transplantation, 69(12), 2593-2600. https://doi.org/10.1097/00007890-200006270-00020