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Antibodies directed to pig non‐Gal antigens in naïve and sensitized baboons
Author(s) -
Ezzelarab Mohamed,
Hara Hidetaka,
Busch Jamie,
Rood Pleunie P. M.,
Zhu Xiaocheng,
Ibrahim Zuhaib,
Ball Suyapa,
Ayares David,
Awwad Michel,
Cooper David K. C.
Publication year - 2006
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2006.00320.x
Subject(s) - peripheral blood mononuclear cell , antibody , cytotoxicity , baboon , antigen , immunology , cytotoxic t cell , xenotransplantation , biology , immune system , microbiology and biotechnology , transplantation , medicine , endocrinology , in vitro , biochemistry
Background: As pigs homozygous for α 1,3‐galactosyltransferase gene‐knockout (GT‐KO) are available, primate antibodies to pig non‐Gal antigens can be studied. Methods: Sera from 56 baboons were tested for binding of IgM and IgG to peripheral blood mononuclear cells (PBMC) from both wild‐type (WT) and GT‐KO pigs by flow cytometry. Complement‐dependent cytotoxicity was measured in 39 sera. Antibody and cytotoxicity responses were measured in two baboons exposed to a GT‐KO pig heart, one not immunosuppressed and one that received only cobra venom factor. Results: IgM and IgG bound to 95% and 79% of WT PBMC, and 32% and 9% GT‐KO PBMC, respectively (WT vs. GT‐KO, P < 0.01). Whereas 97% of sera were cytotoxic to WT PBMC, only 64% were cytotoxic to GT‐KO PBMC, and the level of cytotoxicity was less (mean 60% vs. 25% lysis, P < 0.05). In the two baboons exposed to GT‐KO hearts, anti‐non‐Gal antibodies increased markedly, peaking after 2 (IgM) and 3 (IgG) weeks, associated with an increase in lysis of GT‐KO PBMC. Conclusions: Two‐thirds of baboon sera demonstrated cytotoxicity to GT‐KO PBMC. After GT‐KO organ transplantation, if an elicited antibody response develops, it is likely to cause rapid graft rejection.