Residual immune response towards decellularized homografts may be highly individual
| Autor: | Dmitry Bobylev, Axel Haverich, Johannes Ebken, Andres Hilfiker, Tobias Goecke, Murat Avsar, Samir Sarikouch, Nils Mester, Dietmar Böthig, Ramadan Jashari, Alexander Horke, Serghei Cebotari, Isabel Smart, Robert Ramm, Igor Tudorache |
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| Rok vydání: | 2020 |
| Předmět: |
Heart Defects
Congenital Male Pulmonary and Respiratory Medicine Arbitrary unit Dot blot 030204 cardiovascular system & hematology Andrology 03 medical and health sciences 0302 clinical medicine Immune system ABO blood group system medicine.artery Translational Research medicine Humans Transplantation Homologous Heart valve replacement Decellularization Pulmonary Valve Aorta Lung biology AcademicSubjects/MED00920 business.industry Immunogenicity Immunity General Medicine Allografts medicine.anatomical_structure 030228 respiratory system Homograft Aortic Valve biology.protein Eacts/106 Female Surgery Eacts/108 Antibody Cardiology and Cardiovascular Medicine business Eacts/125 Eacts/103 |
| Zdroj: | European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery |
| ISSN: | 1873-734X 1010-7940 |
| Popis: | OBJECTIVES Decellularized homograft valves (DHVs) have shown promising clinical results, particularly in the treatment of congenital heart disease. However, DHV appears to elicit an immune response in a subset of young patients, indicated by early valve degeneration. As the decellularization process is quality controlled for each DHV, we hypothesized that there may be residual immunogenicity within the extracellular matrix of DHV. METHODS A semi-quantitative dot blot analysis was established to screen for preformed recipient antibodies using secondary anti-human antibodies. Fifteen DHV samples (7 aortic, 8 pulmonary) were solubilized and exposed to serum from 20 healthy controls. RESULTS The sera from young controls (n = 10, 18–25 years) showed significantly stronger binding of preformed antibodies than sera from older individuals (n = 10, 48–73 years). The difference between the means of arbitrary units was 15.1 ± 6.5 (P = 0.0315). There was high intraindividual variance in the mean amounts of arbitrary units of antibody binding with some healthy controls showing >10 times higher antibody binding towards 2 different DHV. The amount of preformed antibodies bound to DHVs was higher in aortic than in pulmonary DHVs. The mean number of antibody binding (in arbitrary units) was 17.2 ± 4.5 in aortic and 14.5 ± 4.7 in pulmonary DHV (P = 0.27). The amount of preformed antibodies bound to pulmonary DHVs was statistically significantly higher in the sera of healthy males (n = 10) than in the sera of healthy females (n = 10). The mean number of arbitrary units was 17.2 ± 4.2 in male and 11.7 ± 5.3 in female sera (P = 0.036). Antibody binding to aortic DHV was also higher in males, but not significant (18.8 ± 5.0 vs 15.6 ± 4.0). Blood group (ABO) incompatibility between the serum from controls and DHV showed no impact on antibody binding, and there was no age-related impact among DHV donors. CONCLUSIONS Residual immunogenicity of decellularized homografts appears to exist despite almost complete cell removal. The established dot blot method allows a semi-quantitative assessment of the individual immune response towards extracellular DHV components and potentially the possibility of preoperative homograft matching. |
| Databáze: | OpenAIRE |
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