First Author | Chiang TR | Year | 2000 |
Journal | Transplantation | Volume | 69 |
Issue | 12 | Pages | 2593-600 |
PubMed ID | 10910282 | Mgi Jnum | J:63464 |
Mgi Id | MGI:1861036 | Doi | 10.1097/00007890-200006270-00020 |
Citation | Chiang TR, et al. (2000) Anti-Gal antibodies in humans and 1, 3alpha-galactosyltransferase knock-out mice. Transplantation 69(12):2593-600 |
abstractText | BACKGROUND: Due to the absence of alphaGAL 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 alphaGAL 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 microM, 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 anti-GAL IgM was 150 and 750 microM, 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 alphaGAL with an avidity/affinity similar to human anti-GAL antibodies and are able to induce hyperacute rejection of GAL+ heart allografts. |