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Gal-Knockout Bioprostheses Exhibit Less Immune Stimulation Compared to Standard Biological Heart Valves

McGregor, CGA; Kogelberg, H; Vlasin, M; Byrne, GW; (2013) Gal-Knockout Bioprostheses Exhibit Less Immune Stimulation Compared to Standard Biological Heart Valves. The Journal of Heart Valve Disease , 22 (3) pp. 383-390.

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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 α-galactosyltransferase knockout (GTKO) pigs. / Methods: Recipients were immunized prior to implant with keyhole limpet hemocyanin (KLH) conjugated to αGal 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 αGal 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 immunemediated injury and degeneration.

Type: Article
Title: Gal-Knockout Bioprostheses Exhibit Less Immune Stimulation Compared to Standard Biological Heart Valves
Publisher version: https://www.icr-heart.com/?cid=3662
Language: English
Additional information: Copyright © ICR Publishers Ltd 2013.
Keywords: science & technology, life sciences & biomedicine, cardiac & cardiovascular systems, cardiovascular system & cardiology, cardiac & cardiovascular systems, alpha-gal, xenograft rejection, cardiac xenotransplantation, aortic valves, porcine, implantation, replacement, expression, progress, cells
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/1430445
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