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Anti-Neu5Gc and anti-non-Neu5Gc antibodies in healthy humans. PLoS One 2017;12(7):e0180768

Date

07/18/2017

Pubmed ID

28715486

Pubmed Central ID

PMC5513429

DOI

10.1371/journal.pone.0180768

Scopus ID

2-s2.0-85024484627   37 Citations

Abstract

Our group previously investigated the levels of anti-Gal and anti-nonGal IgM and IgG in a cohort of 75 healthy humans of various backgrounds, and found some significant differences related to factors such as age, gender, ABO blood group, diet, vaccination history, and geographic location during childhood. We have now expanded our cohort (n = 84) to investigate the levels of anti-Neu5Gc and anti-nonGal/nonNeu5Gc antibodies in healthy humans. Anti-nonGal and anti-nonGal/nonNeu5Gc human IgM and IgG binding to pRBCs and pAECs from GTKO/CD46 and GTKO/CD46/Neu5GcKO pigs were measured by flow cytometry. Anti-Gal and anti-Neu5Gc IgM and IgG levels were measured by ELISA. In summary, (i) the great majority (almost 100%) of humans had anti-Neu5Gc IgM and IgG antibodies that bound to pAECs and approximately 50% had anti-Neu5Gc antibodies that bound to pRBCs, (ii) there was significantly less human antibody binding to pig cells that did not express either Gal or Neu5Gc compared with those that did not express Gal alone, (iii) the levels of both IgM and IgG binding to GTKO/CD46/Neu5GcKO pRBCs and pAECs were low, (iv) the level of anti-Neu5Gc IgG was higher in men than women, (v) the level did not change with age or diet, and there was some variability associated with (vi) previous vaccination history and (vii) the geographic region in which the individual spent his or her childhood. Our study confirms that human antibody binding to RBCs and AECs from GTKO/CD46/Neu5GcKO pigs is greatly reduced compared to binding to GTKO/CD46 cells. However, all humans appear to have a low level of antibody that binds to pAECs that is not directed to either Gal or Neu5Gc. Our findings require consideration in planning clinical trials of xenotransplantation.

Author List

Gao B, Long C, Lee W, Zhang Z, Gao X, Landsittel D, Ezzelarab M, Ayares D, Huang Y, Cooper DKC, Wang Y, Hara H

Author

Whayoung Lee MD Assistant Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

ABO Blood-Group System
Adult
Aged
Aged, 80 and over
Animals
Antibodies
Cells, Cultured
Diet
Endothelial Cells
Erythrocytes
Female
Galactose
Galactosyltransferases
Humans
Immunoglobulin G
Immunoglobulin M
Male
Membrane Cofactor Protein
Middle Aged
Mixed Function Oxygenases
Neuraminic Acids
Swine
Vaccination
Young Adult