Abstract | BACKGROUND: An initial observation suggested high levels of anti-pig antibodies in healthy humans who had spent their childhood in the Middle East. We tested larger cohorts to determine whether anti-pig antibody levels correlated with the geographic location in which the subject spent his/her childhood, because this might have implications for clinical trials of xenotransplantation. METHODS: Anti-pig IgM and IgG levels (by flow cytometry using peripheral blood mononuclear cells from wild-type and α1,3- galactosyltransferase gene-knockout pigs) and anti-Gal IgM and IgG levels (by enzyme-linked immunosorbent assay) were measured in 75 volunteers. Comparisons of antibody levels were also made based on subject age, gender, ABO blood group, diet, and history of vaccination. RESULTS: Antibody binding to α1,3-galactosyltransferase gene-knockout pig cells was less than to wild-type cells. There was a reduction in anti-pig IgM and anti-Gal IgM, but a slight increase in anti-nonGal IgG, with age. Women had higher levels of anti-Gal IgM than men. Blood group A subjects had higher levels of anti-pig IgM and IgG than those of group AB. Diet had no influence on antibody levels. Typhoid or measles- mumps- rubella vaccination was associated with lower anti-nonGal IgG or anti-Gal IgG, respectively, whereas influenza vaccination was associated with higher anti-nonGal IgG. There were some significant variations in antibody levels associated with location during childhood, with subjects from the Middle East demonstrating higher anti-nonGal IgG and anti-Gal IgG. CONCLUSION: Clinical trials of xenotransplantation may be influenced by various factors, including the geographic location of the recipient during childhood, possibly associated with exposure to different microorganisms.
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Authors | Goutham Kumar, Vikas Satyananda, Jason Fang, Hao Zhou, Minoru Fujita, Burcin Ekser, Cassandra Long, Eefje Dons, Qing Sun, David Ayares, Hidetaka Hara, David K C Cooper |
Journal | Transplantation
(Transplantation)
Vol. 96
Issue 4
Pg. 387-93
(Aug 27 2013)
ISSN: 1534-6080 [Electronic] United States |
PMID | 23887601
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- ABO Blood-Group System
- Antibodies, Heterophile
- Immunoglobulin G
- Immunoglobulin M
- Galactosyltransferases
- N-acetyllactosaminide alpha-1,3-galactosyltransferase
- Galactose
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Topics |
- ABO Blood-Group System
- Adult
- Aged
- Animals
- Antibodies, Heterophile
(blood)
- Child
- Cohort Studies
- Female
- Galactose
(immunology)
- Galactosyltransferases
(deficiency, genetics)
- Gene Knockout Techniques
- Humans
- Immunoglobulin G
(blood)
- Immunoglobulin M
(blood)
- Leukocytes, Mononuclear
(enzymology, immunology)
- Male
- Middle Aged
- Middle East
(ethnology)
- Sus scrofa
(genetics, immunology, metabolism)
- United States
- Young Adult
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