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Galili, Uri1,2; LaTemple, Denise C.1; Walgenbach, Ann W.3; Stone, Kevin R.3

Experimental Transplantation

The recent advances in avoiding hyperacute rejection by producing transgenic pigs with complement regulatory proteins call for the analysis of posttransplantation changes in anti-Gal activity in the absence of hyperacute rejection. Transplantation of cynomolgus monkeys with porcine or bovine meniscus and articular cartilage enabled the study of anti-Gal IgG response to xenografts that are not subjected to hyperacute rejection. The cartilage implants were kept in suprapatellar pouches of the recipients for 1 or 2 months and anti-Gal activity was measured in the serum at various time intervals after transplantation. Within 2 weeks after transplantation, titer of anti-Gal IgG, in all transplanted monkeys, increased by 20- to 100-fold, as measured in ELISA with synthetic α-galactosyl epitopes linked to bovine serum albumin or with mouse laminin. Furthermore, binding of serum anti-Gal to porcine endothelial cells increased by 10-fold or more after transplantation. Complement-mediated cytotoxicity also increased by two- to eightfold after transplantation. The elevated activity of anti-Gal was maintained for the 2-month period during which the grafts were kept in the monkeys, and returned to the pretransplantation level 6 months after graft removal. All these data suggest that the primate immune system responds vigorously to α-galactosyl epitopes on xenografts by activating many B lymphocytes that produce increased amounts of anti-Gal IgG, which may also be of high affinity. These antibodies are likely to bind to the xenograft cells, even if these cells express low numbers of α-galactosyl epitopes. Such antibody binding may play an important role in chronic rejection of xenografts.

Department of Microbiology and Immunology, MCP-Hahnemann School of Medicine, Allegheny University, Philadelphia, Pennsylvania, and The Stone Clinic, San Francisco, California

1 Department of Microbiology and Immunology, MCP-Hahnemann School of Medicine.

2 Address correspondence to: Dr. Uri Galili, Department of Microbiology and Immunology, MCP-Hahnemann School of Medicine, Allegheny University, 2900 Queen Lane, Philadelphia, PA 19129.

3 The Stone Clinic.

Received 18 July 1996.

Accepted 10 October 1996.

© Williams & Wilkins 1997. All Rights Reserved.