The role of anti-pig antibody in pig-to-baboon cardiac xenotransplant rejection

Abstract

The role of naturally produced antibody in discordant xenograft rejection is still uncertain. Twelve orthotopic pig-to-baboon heart transplants (HTx) were performed. In 2 baboons, no antibody adsorption (AbA) was performed. In 5 baboons, AbA with a pig lung was performed during circulatory arrest. In 5 baboons, AbA and blood exsanguination at the beginning of cardiopulmonary bypass (CPB) were performed. Baboons were divided into 2 groups; group 1 (n = 4) died within 24 hr of HTx and group 2 (n = 8) survived more than 24 hr. Mean survival period was 9.8 +/- 3.0 hr in group 1 and 151 +/- 33 hr in group 2. Baboon anti-pig antibody (Ab) was measured before CPB, before circulatory arrest, during AbA, at the end of CPB, and daily after HTx. Anti-RBC Ab was measured by the titration method at temperatures of 4 degrees C and 37 degrees C (RAb-4 and RAb-37). Anti-endothelial cell Ab (EAb) and anti-white blood cell Ab (WAb) titers were measured with ELISA. RAb titration > or = 1/4 and EAB and WAb > or = 1/256 were determined to be seropositive (S(+)). S(+) rate of RAb-37 at the end of CPB (endCPB) in group 2 was significantly higher than that in group 1 (8/8 vs. 1/4; P < 0.05). The seronegative (S(-)) rates of RBC-4 and EAb (endCPB) in group 2 were higher than those in group 1 (7/8 vs. 1/4 and 6/8 vs. 1/4, respectively), but not significantly. There was no difference in S(-) rate of WAb (endCPB) between group 1 and group 2. More than 4-fold decrease in RAb-4 and RAb-37 by AbA with a pig lung was observed in 5 and 7 of 8 baboons, while EAb and WAb did not change by AbA. In all of group 2, RAb-4 reverted to S(+) within 3 days after HTx. One baboon had no rejection episode and died of infection 16 days after HTx (baboon 16); however, it also became S(+) for RAb-4 a day after HTx until death. In 4 of group 2, RAb-37 became S(+) 1 or 2 days before death by rejection. Baboon 16, however, became S(+) for RAb-37 7 days after HTx and S(-) again 9 days after HTx until death. EAb became S(+) in all of group 2, but 5 of them survived more than 5 days after seroconversion.(ABSTRACT TRUNCATED AT 400 WORDS)