Share this page on LinkedIn
Share This Page on Google+
Share This Page on Twitter
tell someone about this page print this page
You are here: Contents > 2013 > Volume 22 Number 3 May 2013 > DEVICE EVALUATION > Gal-Knockout Bioprostheses Exhibit Less Immune Stimulation Compared to Standard Biological Heart Valves

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

Christopher G. A. McGregor1,2, Heide Kogelberg1, Michal Vlasin2,3,4, Guerard W. Byrne1,2

1Institute of Cardiovascular Sciences, University College London, UK, 2Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA, 3University of Veterinary and Pharmaceutical Sciences Brno, 4International Clinical Research Centre (ICRC) Brno, Czech Republic

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.

The Journal of Heart Valve Disease 2013;22:383-390

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

Click the above hyperlink to view the article, right click (Ctrl click on a Mac) to open in a new browser window or tab.

Purchase this Article

Please click the button below to purchase this article. Single article purchases are provided at $50.00 per article. Upon clicking the button below, single article user account subscription details are requested and, upon successful payment, a single article user account is created. Single articles are availble in your account for seven days after purchase.