Neutralization of blood group A-antigen by a novel anti-A antibody: Overcoming ABO-incompatible solid-organ transplantation

被引：14

作者：

Hasegawa, Yasushi ^{[1
,2
]}

Kato, Yukinari ^{[2
]}

Kaneko, Mika Kato ^{[2
]}

Ogasawara, Satoshi ^{[2
]}

Shimazu, Motohide ^{[3
]}

Tanabe, Minoru ^{[1
]}

Kawachi, Shigeyuki ^{[1
]}

Obara, Hideki ^{[1
]}

Shinoda, Masahiro ^{[1
]}

Kitagawa, Yuko ^{[1
]}

Narimatsu, Hisashi ^{[2
]}

Kitajima, Masaki ^{[4
]}

机构：

[1] Natl Inst Adv Ind Sci & Technol, Res Ctr Med Glycosci, Tsukuba, Ibaraki 3058568, Japan

[2] Keio Univ, Sch Med, Dept Surg, Tokyo 160, Japan

[3] Tokyo Med Univ, Hachioji Med Ctr, Dept Digest Surg, Tokyo, Japan

[4] Int Univ Hlth &Welfare, Mita Hosp, Dept Surg, Tokyo, Japan

来源：

TRANSPLANTATION | 2008年 / 85卷 / 03期

关键词：

ABO-incompatible organ transplantation; neutralization of blood group antigen; antiblood group antibody; Fab fragment;

D O I：

10.1097/TP.0b013e3181612f84

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：378 / 385

页数：8

共 26 条

[1]

Bühler L, 2000, TRANSPLANTATION, V70, P1323

[2]

DEMETRIS AJ, 1988, AM J PATHOL, V132, P489

[3] THE BINDING-SITE FOR CLQ ON IGG [J].