Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: implications for xenotransplantation in infants.
If an ABO-incompatible heart is transplanted into an infant before natural antibodies have developed to the specific donor carbohydrate A/B antigen(s), then B-cell tolerance to the donor A/B antigen is achieved, and these antibodies never develop. Anti-carbohydrate antibodies play a role in the rejection of wild type (WT) and alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig xenografts. We investigated development of these antibodies in infant baboons and humans. Serum samples from infant baboons (n = 42) and humans (n = 42) were tested by flow cytometry for immunoglobulin M and immunoglobulin G binding to peripheral blood mononuclear cells from WT and GT-KO pigs, and for complement-dependent cytotoxicity. The presence of anti-blood group antibodies was tested in baboon serum. In infant baboons and humans, cytotoxic anti-Galalpha1,3Gal antibodies develop during the first 3 months, and steadily increase with age, whereas cytotoxic anti-nonGal antibodies are either absent or minimal in the majority of cases throughout the first year of life. Anti-blood group antibodies were not detected before 16 weeks of age. Our data suggest GT-KO pig organ/cell transplants could be carried out in early infancy in the absence of preformed cytotoxic anti-nonGalalpha1,3Gal antibodies.
Rood
Pleunie P M
PP
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Tai
Hao-Chih
HC
Hara
Hidetaka
H
Long
Cassandra
C
Ezzelarab
Mohamed
M
Lin
Yih J
YJ
van der Windt
Dirk J
DJ
Busch
Jamie
J
Ayares
David
D
Ijzermans
Jan N M
JN
Wolf
Roman F
RF
Manji
Rizwan
R
Bailey
Leonard
L
Cooper
David K C
DK
D000017:ABO Blood-Group System / Q000276:immunology; D000818:Animals; D030801:Animals, Genetically Modified / Q000276:immunology; D000917:Antibody Formation / Q000502:physiology; D002657:Child Development / Q000502:physiology; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D005700:Galactosyltransferases / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D023421:Models, Animal; D010215:Papio; D013552:Swine / Q000235:genetics / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology
D000017:ABO Blood-Group System; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D005700:Galactosyltransferases