About: Gal-Knockout Bioprostheses Exhibit Less Immune Stimulation Compared to Standard Biological Heart Valves     Goto   Sponge   NotDistinct   Permalink

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  • 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 alpha Gal to match the anti-Gal levels and isotypes found in humans. Stented glutaraldehydefixed 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 alpha Gal antigen.
  • 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 alpha Gal to match the anti-Gal levels and isotypes found in humans. Stented glutaraldehydefixed 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 alpha Gal antigen. (en)
Title
  • 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 (en)
skos:prefLabel
  • 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 (en)
skos:notation
  • RIV/00159816:_____/13:00060576!RIV14-MSM-00159816
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • P(ED1.100/02/0123)
http://linked.open...iv/cisloPeriodika
  • 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 76156
http://linked.open...ai/riv/idVysledku
  • RIV/00159816:_____/13:00060576
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • cells; progress; expression; replacement; implantation; porcine; aortic valves; cardiac xenotransplantation; xenograft rejection; alpha-gal (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV
  • [EAFF79467188]
http://linked.open...i/riv/nazevZdroje
  • Journal of heart valve disease
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 22
http://linked.open...iv/tvurceVysledku
  • Vlašín, Michal
  • Byrne, Guerard W.
  • Kogelberg, Heide
  • McGregor, Christopher G. A.
http://linked.open...ain/vavai/riv/wos
  • 000321722100015
issn
  • 0966-8519
number of pages
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