1887

Abstract

Abstract

As immune responses likely contribute to degeneration of bioprosthetic heart valves (BHVs), this nonhuman primate study compares the anti-Gal antibody response to BHVs from wild type (WT) pigs (current BHVs) and those from α-galactosyltransferase knockout (GTKO) pigs. Stented glutaraldehyde fixed BHVs from WT (n=4) and GTKO (n=3) pigs were commercially manufactured and implanted in the mitral position in nonhuman primates using standard surgical techniques. Recipients were treated with Lovenox (1mg/kg BID) for 5 weeks reducing to 1mg/kg daily for one week and then discontinued. Recipients were sensitized to the αGal antigen by immunization to match IgG levels found in humans. Serum antibody responses were monitored by ELISA. WT BHVs were explanted at 3 hours, 1 year, 2 years and the fourth is currently ongoing at 3 years. One GTKO BHV was explanted at 218 days. The remaining two GTKO BHVs are currently ongoing at 3 years. After immunization, circulating anti-Gal IgG levels were comparable in both groups at the time of implantation and were equal or greater than human levels. Anti-Gal antibody levels decreased in both WT and GTKO recipients after implantation. WT recipients, however, retained elevated levels (greater than 20% preimplant values) of anti-Gal IgG for at least the first year post implant. Conversely anti-Gal IgG levels in all GTKO recipients fell within one month and remained at less than 20% preimplant values. Analysis of the area under the curve showed a significant increase of anti-Gal IgG in the WT BHV group compared to GTKO BHV recipients (p<0.01). In this nonhuman primate model, the persistently and significantly (p<0.01) elevated levels of anti-Gal IgG antibody observed in WT but not GTKO BHV recipients, indicate continuing immune stimulation to the αGal antigen. Current commercially available BHVs are similarly known to contain αGal antigen. Anti-Gal antibody has been shown to increase calcification of processed pericardium in the rat implant model. These data support the hypothesis that preformed and induced anti-Gal antibody in BHV recipients may initiate an early immune response, which promotes subsequent calcification. BHVs made from GTKO pigs would eliminate this major xenoreactive antigen and provide a prosthesis with reduced immunogenicity. Such BHVs made from GTKO pigs may have greater durability and be potentially used in younger patients with more active immune systems.

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/content/papers/10.5339/qproc.2012.heartvalve.4.61
2012-05-01
2019-12-05
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http://instance.metastore.ingenta.com/content/papers/10.5339/qproc.2012.heartvalve.4.61
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  • Accepted: 03 June 2012
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