{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:16:19Z","timestamp":1790712979331,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,1,5]],"date-time":"2005-01-05T00:00:00Z","timestamp":1104883200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2002<\/jats:bold> The \u03b1\u2010Gal (Gal\u03b11,3\u2010Gal\u03b21\u20134GlcNAc\u2010R) 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 \u03b1\u2010Gal immune response may play a role in this clinical scenario.<\/jats:p><jats:p><jats:bold>Materials and methods\u2002<\/jats:bold> We investigated the presence of \u03b1\u2010Gal\u2010epitope 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\u2010existing cytotoxic anti \u03b1\u2010Gal IgM antibodies within 10\u00a0days of surgery. Patients who underwent coronary artery bypass grafting (CABG) or mechanical valve replacement served as controls (each group, <jats:italic>n<\/jats:italic>\u00a0=\u00a012). To corroborate the clinical relevance of the \u03b1\u2010Gal immune response <jats:italic>in vivo<\/jats:italic>, we studied serum obtained before and after implantation of bioprostheses and its potency to lyse porcine \u03b1\u2010Gal\u2010bearing PK15 cells.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> We found the immunogenic \u03b1\u2010Gal\u2010epitope 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 \u03b1\u2010Gal after surgical intervention as compared with control patients (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00\u00b70001, respectively). Sera obtained from the patients after the implantation of bioprostheses demonstrated an increased cytotoxicity against \u03b1\u2010Gal\u2010bearing PK\u201015 cells as compared with preoperative sera (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00\u00b7001). The specificity of the cytotoxic effects was proven as soluble Gal\u03b11\u20133Gal\u03b21\u20134GlcNAc markedly inhibited cell death of \u03b1\u2010Gal\u2010bearing PK15 cells (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00\u00b7001).<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> Our data suggest that implantation of bioprostheses in cardiac surgery induces a xenograft\u2010specific immune response. Procedures diminishing the presence of \u03b1\u2010Gal on bioprostheses, such as utilization of genetically manipulated \u03b1\u2010Gal\u2010deficient xenograft or pretreatment with \u03b1\u2010Galactosidase, might diminuate the immune response against bioprostheses and extend durability.<\/jats:p>","DOI":"10.1111\/j.1365-2362.2005.01441.x","type":"journal-article","created":{"date-parts":[[2005,1,5]],"date-time":"2005-01-05T16:24:40Z","timestamp":1104942280000},"page":"17-23","source":"Crossref","is-referenced-by-count":216,"title":["Alpha\u2010Gal on bioprostheses: xenograft immune response in cardiac surgery"],"prefix":"10.1111","volume":"35","author":[{"given":"K.","family":"Z. Konakci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Bohle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Blumer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Hoetzenecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Moser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Boltz\u2010Nitulescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Gorlitzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Klepetko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Wolner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. J.","family":"Ankersmit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,1,5]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(01)01294-9"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199108000-00006"},{"key":"e_1_2_7_4_2","doi-asserted-by":"crossref","first-page":"11391","DOI":"10.1073\/pnas.90.23.11391","article-title":"Anti\u2010pig IgM antibodies in human serum react predominantly with gal (alpha1\u20133) gal epitopes","volume":"90","author":"Sandrin MS","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.5.1369"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.162.2.573"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199312000-00031"},{"key":"e_1_2_7_8_2","first-page":"559","article-title":"Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans","volume":"24","author":"Good AH","year":"1992","journal-title":"Transplant Proc"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.56.7.1730-1737.1988"},{"key":"e_1_2_7_10_2","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S0022-5223(19)43204-2","article-title":"Heterograft aortic valves for human use. Valve bank, techniques of measurement, and implantation","volume":"53","author":"O'Brien MF","year":"1967","journal-title":"J Thorac Cardiovasc Surg"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.21.2.115"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(78)90873-1"},{"key":"e_1_2_7_13_2","unstructured":"HannahH3rd ReisRL.Current status of porcine heterograft prostheses: a 5\u2010year appraisal.Circulation1976:54:III 27\u201331."},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(98)00454-9"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(80)80022-1"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(10)65888-2"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01680633"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1067\/mtc.2000.106526"},{"key":"e_1_2_7_19_2","first-page":"137","article-title":"Monoclonal antibodies specific for vimentin","volume":"34","author":"Osborn M","year":"1984","journal-title":"Eur J Cell Biol"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1067\/mtc.2003.76"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-3274(97)80024-X"},{"issue":"3","key":"e_1_2_7_22_2","first-page":"199","article-title":"Inflammatory and Immune Processes: The Neglected Villain of Bioprosthetic Degeneration?","volume":"11","author":"Human P","year":"2001","journal-title":"J Long-Term Effects Med Implants"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1078942"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2362.2005.01441.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2362.2005.01441.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T16:58:31Z","timestamp":1697216311000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2362.2005.01441.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,1]]}},"alternative-id":["10.1111\/j.1365-2362.2005.01441.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2362.2005.01441.x","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"value":"0014-2972","type":"print"},{"value":"1365-2362","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,1]]}}}