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Title: Human HLA specific antibodies crossreact with swine leucocyte antigens
Author: Van Dam, Mieke Gerharda
ISNI:       0000 0001 3402 9985
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2002
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Background: Organs transplanted between discordant species such as pig-to-primate, undergo hyperacute rejection due to the presence of natural xenogenic antibodies. Hyperacute rejection xenograft rejection can now be controlled by various approaches, but other immunological barriers have yet to be overcome. Polyspecific HLA antibodies often crossreact with other HLA antigens through so called public and private determinants. Swine leucocyte antigens share approximately 75-87% homology with HLA and as such, it may be expected that some HLA antibodies would react with certain SLA antigens. In an attempt to evaluate this possible occurrence, sera were selected from individuals with varying panel reactive antibodies. Methods: Naturally occurring anti-pig antibodies were absorbed using an excess of leucocyte depleted washed pig red blood cells (PRBC). Anti-HLA/SLA cross reactivity was investigated by 1) testing the pre and post-absorbed sera against a panel of out bred pig splenocytes; 2) HLA class I and II antibodies were absorbed out using pooled EBV cell and human platelets; 3) Human non-Gala1,3Gal antibody was adsorbed onto, then eluted from pig splenocytes. The presence of HLA specific antibody in the eluates was investigated. Results. Natural anti-pig antibody adsorption was confirmed in all sera by flow cytometry against PRBC. Anti-HLA activity was still present and undiminished post-PRBC-adsorption. Some HLA specific sera still reacted against some pigs after removal of natural antibody and no reactivity was identical to any other. Upon absorption of the HLA antibodies, the majority of anti-pig reactivity was abrogated. The eluates showed that HLA class I and II antibodies were eluted from pig splenocytes. In addition, the presence of a non-HLA antibody was also found. Conclusions: The results show that there is cross reactivity between IgG anti-HLA and pig lymphocytes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Xenotransplantation