Neutralization of blood group A-antigen by a novel anti-A antibody: overcoming ABO-incompatible solid-organ transplantation.
BACKGROUND
The major barrier to ABO-incompatible solid-organ transplantation is acute humoral rejection. It is known to be triggered by antidonor blood group A/B antibodies, which might bind to A/B-antigen on the endothelium of the graft. Various strategies to reduce antiblood group antibody by overcoming ABO-incompatible transplantation have been tried. However, antigen-suppressing procedures have not been performed.


METHODS
We produced a novel anti-A antibody (K7508) by immunizing mice with salivary mucin of a blood group A individual, thereby clarifying that blood group A-antigen is expressed in endothelial cells of the liver. We investigated whether K7508 can mask A-antigen on the cells in vitro. Next, we immunized mice with A-antigen-expressing cells coated with K7508 or its Fab fragment, and measured anti-A antibody production in the mice.


RESULTS
Blood group A-antigen-expressing cells, such as blood group A-red blood cells (A-RBCs) and A431 cells, coated with K7508 were not recognized by another anti-A antibody in flow cytometry, indicating that A-antigen was masked by K7508 in vitro. The A-antigen on the paraffin-embedded liver tissue was also masked by K7508. Furthermore, the production of anti-A antibody in mice immunized with A-antigen-expressing cells coated with K7508 or its Fab fragment was significantly suppressed compared to that in mice immunized with non-coated cells alone, indicating that A-antigen was neutralized by K7508 in vivo.


CONCLUSIONS
The neutralization of blood group antigen by antiblood group antibody and especially its Fab fragment might represent one strategy to overcome ABO-incompatible organ transplantation.
Hasegawa
Yasushi
Y
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Kato
Yukinari
Y
Kaneko
Mika Kato
MK
Ogasawara
Satoshi
S
Shimazu
Motohide
M
Tanabe
Minoru
M
Kawachi
Shigeyuki
S
Obara
Hideki
H
Shinoda
Masahiro
M
Kitagawa
Yuko
Y
Narimatsu
Hisashi
H
Kitajima
Masaki
M
D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology*; D001789:Blood Group Antigens / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016377:Organ Transplantation; D012680:Sensitivity and Specificity
D000017:ABO Blood-Group System; D000906:Antibodies; D001789:Blood Group Antigens