Document Detail


Removal of anti-porcine natural antibodies from human and nonhuman primate plasma in vitro and in vivo by a Galalpha1-3Galbeta1-4betaGlc-X immunoaffinity column.
MedLine Citation:
PMID:  9458010     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Natural antibodies (NAbs) against a terminal alpha1-3 galactosyl (alphaGal) epitope have been identified as the major human anti-pig NAbs. METHODS AND RESULTS: We used two synthetic alphaGal trisaccharides--type 6 (alphaGal6) and type 2(alphaGal2)--linked to an inert matrix to remove NAbs from human plasma in vitro. Flow cytometry indicated that an average of 85% of the NAb binding activity was depleted by adsorption with alphaGal6. By measuring the binding of NAbs to pig peripheral blood mononuclear cells and bone marrow cells, we demonstrated that alphaGal6 was more effective than alphaGal2 in removing NAbs, and the combination of alphaGal6 + alphaGal2 did not further increase removal of NAbs. The specificity of the removal of NAbs (IgM and IgG) reactive with the alphaGal epitope by alphaGal6 matrix was shown by enzyme-linked immunosorbent assay. In vivo studies in nonhuman primates compared plasma perfusion through a alphaGal6 immunoaffinity column with hemoperfusion through a pig liver for changes in blood pressure, hematocrit, platelets, and NAb adsorption. CONCLUSIONS: Both methods reduced the level of anti-pig IgM and IgG xenoreactive antibodies to nearly background, but column perfusion caused less hypotension and reduction in platelets than liver perfusion. Four pig kidneys transplanted into monkeys after column perfusion did not undergo hyperacute rejection, remaining functional for 2-10 days, with a mean functional period of 7 days, demonstrating that a pig kidney can support renal function in a primate.
Authors:
Y Xu; T Lorf; T Sablinski; P Gianello; M Bailin; R Monroy; T Kozlowski; M Awwad; D K Cooper; D H Sachs
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  65     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-02-11     Completed Date:  1998-02-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  172-9     Citation Subset:  IM    
Affiliation:
BioTransplant Inc., Boston, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / immunology,  isolation & purification*
Chromatography, Affinity
Epitopes / immunology*
Female
Graft Rejection / immunology
Humans
Immunosorbents
Kidney Transplantation / immunology
Macaca fascicularis
Male
Papio
Plasma / chemistry,  immunology*
Primates
Sensitivity and Specificity
Swine
Transplantation, Heterologous / immunology*
Trisaccharides / immunology*
Chemical
Reg. No./Substance:
0/Antibodies; 0/Epitopes; 0/Immunosorbents; 0/Trisaccharides; 0/alpha-galactosyl epitope

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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