Cobra venom factor stimulates anti-alpha-galactose antibody production in baboons. Implications for pig-to-human xenotransplantation.
Cobra venom factor (CVF) depletes complement and may therefore be of use in preventing the hyperacute rejection that follows discordant organ xenotransplantation. In two baboons studied, the intramuscular injection of CVF (0.25 mg/kg) was followed by a marked reduction in serum C3 and CH50, and serum cytotoxicity to pig kidney (PK15) cells. There was, however, a very rapid rise in the level of anti-alpha-galactose (alpha Gal) antibody, and a slower rise in anti-CVF antibody. A second intramuscular injection of CVF on day 14 was ineffective in reducing C3, CH50, and serum cytotoxicity. The major oligosaccharide of CVF is known to contain alpha Gal residues, which we suggest stimulate the major increase in anti-alpha Gal antibody level seen in the present study. In the clinical situation, this might lead to an increased immune response to a concomitantly transplanted pig organ.
Taniguchi
S
S
Oklahoma Transplantation Institute, Baptist Medical Center, Oklahoma City, USA.
Kobayashi
T
T
Neethling
F A
FA
Ye
Y
Y
Niekrasz
M
M
White
D J
DJ
Cooper
D K
DK
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D015941:Complement Hemolytic Activity Assay; D003602:Cytotoxicity, Immunologic; D004546:Elapid Venoms / Q000276:immunology / Q000494:pharmacology*; D005690:Galactose / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D010215:Papio; D013268:Stimulation, Chemical; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D003176:Complement C3; D003181:Complement C4; D004546:Elapid Venoms; C016310:cobra venom factor; D005690:Galactose