Alpha-Gal on bioprostheses: xenograft immune response in cardiac surgery

• Published in: European journal of clinical investigation 2005-01, Vol.35 (1), p.17-23
• Main Authors: Z. Konakci, K., Bohle, B., Blumer, R., Hoetzenecker, W., Roth, G., Moser, B., Boltz-Nitulescu, G., Gorlitzer, M., Klepetko, W., Wolner, E., Ankersmit, H. J.
• Format: Article
• Language: English
• Subjects: 3-galactose; 3-Galβ1-4GlcNAc-R; alpha-gal antibody; Animals; Antibodies - blood; Antigens, Heterophile - immunology; Aortic Valve Stenosis - surgery; Biological and medical sciences; bioprostheses; Bioprosthesis; cardiac surgery; Coronary Disease - surgery; degeneration; Enzyme-Linked Immunosorbent Assay - methods; Epitopes; galactose α1; Galα1; General aspects; Graft Rejection - immunology; Heart Valve Prosthesis Implantation; Humans; immune response; Immunity, Cellular; Medical sciences; Primates; Prosthesis-Related Infections - immunology; Swine; Transplantation, Heterologous; xenotransplantation; α-Gal
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2005.01441.x

Background  The α‐Gal (Galα1,3‐Galβ1–4GlcNAc‐R) epitope is the major xenoantigen causing hyperacute rejection of pig organs transplanted into primates. Porcine bioprostheses are utilized in cardiac surgery. However, premature degeneration of bioprostheses has limited utilization in younger patients and the immune response remains elusive. We sought to investigate whether a specific α‐Gal immune response may play a role in this clinical scenario. Materials and methods  We investigated the presence of α‐Gal‐epitope on native and fixed porcine valves by means of confocal laser scanning microscope (CLSM). ELISA was utilized to evidence whether implantation of bioprostheses elicits augmentation of pre‐existing cytotoxic anti α‐Gal IgM antibodies within 10 days of surgery. Patients who underwent coronary artery bypass grafting (CABG) or mechanical valve replacement served as controls (each group, n = 12). To corroborate the clinical relevance of the α‐Gal immune response in vivo, we studied serum obtained before and after implantation of bioprostheses and its potency to lyse porcine α‐Gal‐bearing PK15 cells. Results  We found the immunogenic α‐Gal‐epitope on fibrocytes interspersed in the connective tissue of porcine valves as determined by vimentin/IB4 lectin binding. Moreover, patients who were provided with a bioprostheses had developed a significant increase of naturally occurring cytotoxic IgM antibodies directed towards α‐Gal after surgical intervention as compared with control patients (P