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. 2013 Aug 27;96(4):387-93.
doi: 10.1097/TP.0b013e3182992a84.

Is there a correlation between anti-pig antibody levels in humans and geographic location during childhood?

Goutham Kumar  1 , Vikas Satyananda, Jason Fang, Hao Zhou, Minoru Fujita, Burcin Ekser, Cassandra Long, Eefje Dons, Qing Sun, David Ayares, Hidetaka Hara, David K C Cooper
Affiliations

Is there a correlation between anti-pig antibody levels in humans and geographic location during childhood?

Goutham Kumar et al. Transplantation. .

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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Conflict of interest statement

Disclosure of Conflict of Interest: David Ayares is an employee of Revivicor Inc.

There are no other conflicts of interest for all the rest of the authors.

Figures

Figure 1
Figure 1. Human IgM and IgG binding to WT and GTKO pig PBMC (n=75)
One-sample t-test was used to compare the relative (r) MFI in IgM and IgG binding between WT and GTKO pPBMC. There were significant differences in both IgM and IgG binding between WT and GTKO pPBMC. (IgM mean rMFI 5.27 vs 1.56; p<0.001; IgG mean rMFI 1.97 vs 1.31; p<0.001).
Figure 2
Figure 2. Relationship between IgM and IgG antibody levels
(A) There was a statistically positive correlation between IgM and IgG binding to GTKO pPBMC (p<0.001), but not to WT pPBMC (p=0.58) (Pearson correlation coefficient.) (B) There was no correlation between the levels of anti-Gal IgM and IgG as measured by ELISA
Figure 3
Figure 3. Anti-pig IgM (A) and IgG (B) antibody levels in sera from subjects from different geographic regions
Subjects from Japan had a higher mean anti-pig IgM than those from Europe, North and South America, and South East Asia. Subjects from South Asia had a higher mean anti-pig IgM than those from Europe and South East Asia. Mean anti-nonGal IgG in subjects from Middle-Eastern countries was significantly higher than in subjects from all other geographic regions (p<0.05) except Japan. Mean anti-Gal IgG was also higher in the Middle-Eastern group than in all other groups (p<0.01) except South East Asia. There were no other significant differences.
Figure 3
Figure 3. Anti-pig IgM (A) and IgG (B) antibody levels in sera from subjects from different geographic regions
Subjects from Japan had a higher mean anti-pig IgM than those from Europe, North and South America, and South East Asia. Subjects from South Asia had a higher mean anti-pig IgM than those from Europe and South East Asia. Mean anti-nonGal IgG in subjects from Middle-Eastern countries was significantly higher than in subjects from all other geographic regions (p<0.05) except Japan. Mean anti-Gal IgG was also higher in the Middle-Eastern group than in all other groups (p<0.01) except South East Asia. There were no other significant differences.
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