AI Article Synopsis
- The study aimed to investigate the immune responses to biological heart valves (BHVs) made from wild-type (WT) pigs compared to those from alpha-galactosyltransferase knockout (GTKO) pigs, focusing on the effects of the xenogeneic antigen Gal.
- Recipients of both types of BHVs showed reduced levels of anti-Gal and anti-KLH antibodies after implantation; however, WT BHV recipients maintained higher anti-Gal IgG levels over the first year compared to GTKO recipients, indicating ongoing immune stimulation.
- The findings suggest that using Gal-positive xenogeneic bioprosthetic materials can provoke a sustained anti-Gal antibody response, highlighting potential implications for the clinical use of these devices.
Article Abstract
Background And Aim Of The Study: Current biological heart valves (BHVs) contain the major xenogeneic antigen Gal. Recipient anti-Gal antibody binding to such an implanted BHV may contribute to valve degeneration. The study aim was to compare, by implantation in non-human primates, the immune consequences of BHVs from Gal-positive wild-type (WT) pigs and those from alpha-galactosyltransferase knockout (GTKO) pigs.
Methods: Recipients were immunized prior to implant with keyhole limpet hemocyanin (KLH) conjugated to alphaGal to match the anti-Gal levels and isotypes found in humans. Stented glutaraldehyde-fixed BHVs from WT (n = 4) and GTKO (n = 3) pigs were commercially manufactured and implanted in the mitral position in non-human primates. Recipients were treated with enoxaparin (1 mg/kg b.i.d.) for five weeks which was tapered, and then discontinued. Serum antibody levels to Gal and KLH were measured using ELISA.
Results: Overall anti-Gal and anti-KLH antibody levels were decreased in both WT and GTKO BHV recipients after implantation. Serum anti-Gal IgG levels in GTKO BHV recipients fell rapidly within one month, matching the loss of anti-KLH reactivity. There was no significant difference in retention of anti-KLH antibody between the groups. WT BHV recipients retained significantly elevated levels of anti-Gal IgG during the first year post implant. Area under the curve analysis showed that anti-Gal IgG was significantly increased in the WT BHV group compared to GTKO BHV recipients (p < 0.01).
Conclusion: Persistent and significantly (p < 0.01) elevated levels of anti-Gal IgG were observed in WT but not GTKO BHV non-human primate recipients, and indicated a continuing BHV-specific immune stimulation to the alphaGal antigen. These data support the hypothesis that the clinical use of Gal-positive xenogeneic bioprosthetic materials can induce an anti-Gal antibody response. Bioprosthetic devices prepared from GTKO pig tissue would eliminate immune stimulation to this major xenoreactive antigen, which may reduce the potential of immune-mediated injury and degeneration.
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Article Synopsis
- The study aimed to investigate the immune responses to biological heart valves (BHVs) made from wild-type (WT) pigs compared to those from alpha-galactosyltransferase knockout (GTKO) pigs, focusing on the effects of the xenogeneic antigen Gal.
- Recipients of both types of BHVs showed reduced levels of anti-Gal and anti-KLH antibodies after implantation; however, WT BHV recipients maintained higher anti-Gal IgG levels over the first year compared to GTKO recipients, indicating ongoing immune stimulation.
- The findings suggest that using Gal-positive xenogeneic bioprosthetic materials can provoke a sustained anti-Gal antibody response, highlighting potential implications for the clinical use of these devices.
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