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Description
| - 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)
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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)
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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)
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skos:notation
| - RIV/00159816:_____/13:00060576!RIV14-MSM-00159816
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http://linked.open...avai/riv/aktivita
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http://linked.open...avai/riv/aktivity
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http://linked.open...iv/cisloPeriodika
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http://linked.open...vai/riv/dodaniDat
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http://linked.open...aciTvurceVysledku
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http://linked.open.../riv/druhVysledku
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http://linked.open...iv/duvernostUdaju
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http://linked.open...titaPredkladatele
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http://linked.open...dnocenehoVysledku
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http://linked.open...ai/riv/idVysledku
| - RIV/00159816:_____/13:00060576
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http://linked.open...riv/jazykVysledku
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http://linked.open.../riv/klicovaSlova
| - cells; progress; expression; replacement; implantation; porcine; aortic valves; cardiac xenotransplantation; xenograft rejection; alpha-gal (en)
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http://linked.open.../riv/klicoveSlovo
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http://linked.open...odStatuVydavatele
| - GB - Spojené království Velké Británie a Severního Irska
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http://linked.open...ontrolniKodProRIV
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http://linked.open...i/riv/nazevZdroje
| - Journal of heart valve disease
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http://linked.open...in/vavai/riv/obor
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http://linked.open...ichTvurcuVysledku
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http://linked.open...cetTvurcuVysledku
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http://linked.open...vavai/riv/projekt
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http://linked.open...UplatneniVysledku
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http://linked.open...v/svazekPeriodika
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http://linked.open...iv/tvurceVysledku
| - Vlašín, Michal
- Byrne, Guerard W.
- Kogelberg, Heide
- McGregor, Christopher G. A.
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http://linked.open...ain/vavai/riv/wos
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issn
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number of pages
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