Abstract
Abstract Xenoreactive antibody responses were investigated in non-human primate (NHP) recipients after porcine islet transplantation (pITx). The levels of anti-αGal and anti-nonGal IgG Abs in serial sera of the recipients were measured by ELISA and flow cytometry using GalT-KO porcine endothelial cells (PECs), respectively. We detected an elicited anti-nonGal IgG response in some sera of the recipients. Through a series of work including EP of protein extracts from GalT-KO PECs, Western blot and MALDI-TOF/TOF mass spectrometry, the putative antigen was identified as bovine albumin. The sera positive of anti-nonGal Ab revealed strong IgG binding to both bovine and porcine albumin, but no binding to human albumin by ELISA. When anti-human, bovine and porcine albumin Abs were measured in pre- and post-pITx sera of 29 NHP recipient, the frequencies of the development of anti-porcine albumin IgG Abs were significantly different according to the types of immunosuppression (IS) regimen: 5/5 (100%) receiving conventional IS regimen, 2/2 (100%) receiving anti-CD154 and sirolimus and 2/21 (9.5%) receiving CD40-CD40L blockade, sirolimus and either anti-ICAM-1 or ATG (P<0.0001 vs. other groups, χ2 test). The anti-bovine albumin IgG was also detected in the sera of 6 (67%) from 9 recipients positive for elicited anti-porcine albumin IgG. These experiments indicate that anti-porcine/bovine albumin Abs are elicited in NHP recipients after porcine ITx, which can be prevented by an adequate IS.
Published Version
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