Neutralization of Blood Group A-Antigen by a Novel
Anti-A Antibody: Overcoming ABO-Incompatible
Solid-Organ Transplantation
Yasushi Hasegawa,1,2 Yukinari Kato,2,5 Mika Kato Kaneko,2 Satoshi Ogasawara,2 Motohide Shimazu,3Minoru Tanabe,1 Shigeyuki Kawachi,1 Hideki Obara,1 Masahiro Shinoda,1 Yuko Kitagawa,1Hisashi Narimatsu,2 and Masaki Kitajima4
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 endotheliumof 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 investigatedwhether 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, indicatingthat 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.
Keywords: ABO-incompatible organ transplantation, Neutralization of blood group antigen, Antiblood group antibody, Fab fragment.
(Transplantation 2008;85: 378–385)

This study was supported in part by a grant (17209044) from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan (to M.K.)
by the Osaka Cancer Research Foundation, Japan (M.K.K.), by the
YASUDA Medical Foundation, Japan (Y.K.), Inoue Foundation for
Science, Japan (Y.K.), and by Mitsubishi Pharma Research Foundation,
Japan (Y.K.).
Y.H. and Y.K. contributed equally to this work.
1
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
2
Research Center for Medical Glycoscience, National Institute of Advanced
Industrial Science and Technology, Ibaraki, Japan.
3
Department of Digestive Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.
4
Department of Surgery, International University of Health and Welfare
Mita Hospital, Tokyo, Japan.
5Address correspondence to: Yukinari Kato, M.D., Ph.D., Research Center
for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Central 2, 1–1-1 Umezono, Tsukuba, Ibaraki, 3058568 Japan.
E-mail: yukinari-k@bea.hi-ho.ne.jp
Received 25 September 2007. Revision requested 16 October 2007.
Accepted 23 October 2007.
Copyright © 2008 by Lippincott Williams & Wilkins
ISSN 0041-1337/08/8503-378
DOI: 10.1097/TP.0b013e3181612f84

ciated with ABO-incompatible transplantation is triggered byantigen recognition of antidonor blood group A/B antibodies, which bind to blood group A/B-antigen on the endothelium of the graft. Subsequently, the complement and bloodclotting cascades initiate (2, 5, 6). The classical pathway,
which is a pathway of complement activation, is induced
when the C1q binds to the Fc fragment of the antibody reacted with the antigen (1, 7, 8). In the graft organ, endothelial
damage causes the formation of fibrin thrombi that destroy
the microvasculature, leading to acute graft dysfunction andgraft failure (4, 9, 10).
The preoperative anti-A/B antibody titer has beenreported to be correlated with long-term graft survival in
ABO-incompatible kidney transplantation (11). In ABOincompatible liver transplantation, patients with high titers of antiblood group antibody are also at very high riskof graft failure (12, 13). Various strategies have been developed to overcome ABO-incompatible transplantation,such as plasmapheresis, splenectomy, intensive immunosuppression, anti-CD20 monoclonal antibody, intravenous immunoglobulin, and intraportal infusion therapy,
which have improved transplantation outcomes (14 –19).
These strategies, however, present the risks of infection
and thrombosis. Furthermore, despite these various therapies, outcomes of ABO-incompatible transplantation areworse than those of ABO-identical or compatible transplantation. Recently, the strategy for overcoming ABOincompatible transplantation is mainly the reduction of
antibodies in plasma or the suppression of antibody pro-

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ew alternative therapies exist for organ failure except organ transplantation, but immune response makes transplantation difficult (1). Rejection of organ grafts by immune
response has become a serious problem. Using ABO bloodgroup-identical or compatible grafts is one solution to thisproblem (2, 3). ABO-incompatible solid-organ transplantation is generally avoided: outcomes generally are unfavorable
because of humoral rejection (4, 5). Humoral rejection asso-F© 2008 Lippincott Williams & Wilkins

duction. The outcome of ABO-incompatible transplantation might be more favorable if the blood group antigen on
the graft organ was suppressed and the humoral rejection
were controlled.
For use in this study, we produced a novel anti-A monoclonal antibody, designated as K7508, and performed A-antigen
suppressing procedures. In vitro, A-antigen-expressing cells
such as blood group A-red blood cells (A-RBCs) or A431 were
coated with K7508 or its Fab fragment. Their reactivity to another anti-A antibody was measured using flow cytometry. In
vivo, we immunized mice with A-antigen-expressing cells after
coating them with K7508 or Fab fragment, and then measured
the production of anti-A antibody in mice sera. This in vivo
model using A-antigen-expressing cells might mimic solid organtransplantation.

FIGURE 1. Flow cytometric analyses to measure the binding activity of
the anti-blood group A antibody,
K7508, or its Fab fragment (K7508Fab).
The A, B, O-RBCs or A431 was reactedwith 1 ␮g/mL K7508 or K7508Fab as thefirst antibody, and then reacted with
1/1000 diluted anti-mouse IgG Oregon
Green as the secondary antibody. Boldlines show K7508 or K7508Fab. Shaded
areas show PBS. A-RBCs were stained
strongly using K7508 (A) and K7508
Fab (B). B-RBCs were stained slightly
by K7508 (C) and K7508Fab (D).
O-RBCs were not stained by K7508 (E)or K7508Fab (F). A431 were strongly
stained by K7508 (G) and K7508Fab(H).

Hasegawa et al.

379

MATERIALS AND METHODS
Animals
Female BALB/c mice were obtained (Charles River Japan,
Inc., Kanagawa, Japan); they were used and maintained in atemperature-controlled room with alternating 12-hour light/
dark cycles. The Animal Care and Use Committee of the National Institute of Advanced Industrial Science and Technology approved all mouse manipulations.
Cell Lines, Antibodies, and Tissue Microarrays
An epidermoid carcinoma cell line, A431, which is known toexpress blood group A-antigen, was obtained from Cell Resource Center for Biomedical Research, Tohoku University(Sendai, Japan) (20). The A431 cells were cultured at 37°C in a

380Transplantation • Volume 85, Number 3, February 15, 2008

FIGURE 2. Binding assay of K7508
or its Fab fragment (K7508Fab) in
ELISA. The ELISA plate wells were coatedwith 1 ␮g/mL A, B-trisaccharides, or Hdisaccharides. Either K7508 (A) or
K7508Fab (B) at a concentration of 0.1
␮g/mL was used as the first antibody,followed by 1/1000 diluted anti-mouse
IgG-HRP or anti-mouse IgM-HRP. The
enzymatic reaction was conductedwith a substrate solution containing
TMB. After the reaction was stopped
with 1 M H2SO4, the optical density wasmeasured at 450 nm using an autoplate reader. Data are the mean ⫾ SDof three independent experiments.
*P⬍0.01.

FIGURE 3. Immunohistochemical analysis of liver tissues using K7508 and its Fabfragment (K7508Fab). The K7508 (A, C, andD) and K7508Fab (B) were added to theliver sections, blood group A individual (Aand B), blood group B individual (C), andblood group O individual (D), at a concentration of 0.05 ␮g/ml for 30 min at room
temperature. Biotinylated secondaryanti-mouse IgG was incubated for 30 min
at room temperature followed by theperoxidase-conjugated biotin-streptavidin
complex (Vectastain ABC Kit) for 30 min atroom temperature. Color was developed
using 3,3-diaminobenzidine tetrahydrochloride for 1 min. The sections werecounterstained with Mayer’s hematoxylin.

humidified atmosphere of 5% CO2 and 95% air in RPMI 1640
medium supplemented with 10% heat-inactivated fetal bovine serum (FBS; Sigma, St. Louis, MO), 2 mM L-glutamine(Invitrogen Corp., Carlsbad, CA), 100 units/mL of penicillin,and 100 ␮g/mL of streptomycin (Invitrogen Corp.). From
healthy volunteers, RBCs of blood groups A, B, and O wereextracted. An anti-A monoclonal antibody (IgM) and rabbit
anti-A polyclonal antibody were purchased (Wako Pure
Chemical Industries Ltd., Tokyo, Japan), as were normal livertissue microarrays (Cybrdi Inc., Frederick, MD).

Hybridoma Production
Female BALB/c mice (4 weeks old) were immunized byneck subcutaneous injections of the salivary mucin of theblood group A-individual with Adjuvant Complete Freund(Difco Laboratories, Detroit, MI) to obtain anti-A-antigen,which is attached to protein. One week later, secondary
intraperitoneal immunization was performed. The booster
injection was given intraperitoneally 2 days before spleencells were recovered. The spleen cells were fused with© 2008 Lippincott Williams & Wilkins

mouse myeloma P3U1 cells using polyethylene glycol (Mr4,000); the hybridomas were grown in RPMI 1640 medium
with hypoxanthine, aminopterin and thymidine selection
medium supplement (Sigma). The culture supernatants
were screened using ELISA for binding to the synthetic
A-antigen.
Preparation of Fab Fragment
Papain digestion was performed to obtain the Fab fragmentusing Immobilized Papain (Pierce Biotechnology Inc., Rockford, IL). The 10 mg of anti-A antibody was added to a final
concentration of 20 mM cystein䡠HCl and 10 mM EDTA. The
1.0 mL of sample was mixed with the 0.25 mL of Immobilized
Papain and incubated overnight in a shaker at 37°C. After
separating the immobilized enzyme from the product by
0.22-␮m filter, the whole IgG that was not disassembled by
the enzyme was removed using Amicon Ultra 100 K (Millipore Corp., Tokyo, Japan).
Flow Cytometry
The RBCs or A431 cells were incubated with purified monoclonal antibodies or mice sera (diluted in phosphate-bufferedsaline [PBS]) for 30 min at 4°C. After washing with PBS, diluted secondary antibodies (1:1000): fluorescein-conjugatedgoat IgG fraction to mouse IgM; ␮ chain-specific (MP Biomedicals, Solon, OH) or Oregon Green 488 goat anti-mouse
IgG(H⫹L) (Invitrogen Corp.) were reacted for 30 min at 4°C.
Fluorescence data were collected using a flow cytometer(FACS Caliber; BD Biosciences, Braintree, MA).
Enzyme-Linked Immunosorbent Assay (ELISA)
The A-trisaccharides conjugated to bovine serum albumin(BSA) (Calbiochem Novabiochem Corp., San Diego, CA),FIGURE 4. Blood group A-antigen was
masked using K7508 or its Fab fragment(K7508Fab) in flow cytometry. First,
1⫻106 cells of A-RBCs were coated with 3
␮g of K7508 (A) or 10 ␮g of K7508Fab (B);alternatively, 1⫻105 cells of A431 were
coated with 100 ␮g of K7508 (C) or
K7508Fab (D). Then, another anti-A antibody (A-IgM) diluted 1/100 was used as
the first antibody, followed by anti-mouse
IgM-FITC, diluted 1/1000, as the secondary antibody. Bold lines show cells coatedwith K7508 or K7508Fab, followed by AIgM. Dark shaded areas show A-IgM.
Light shaded areas show PBS as a negative control.

Hasegawa et al.

381

B-trisaccharides conjugated to BSA (Dextra Laboratories,
Reading, UK), and H-disaccharides conjugated to BSA (Dextra Laboratories) were independently coated onto Nuncimmuno plates (Nunc, Roskilde, Denmark) at 1 ␮g/mL for 1
hr. After blocking with 1% BSA, the plates were incubatedwith purified monoclonal antibodies or mice sera for 1 hr.
After washing with 0.05% Tween 20 in PBS, the plates wereincubated with HRP anti-mouse IgG (Dako, Glostrup, Denmark) or peroxidase-conjugated affinipure donkey antimouse IgM, ␮ chain specific (Jackson Immuno ResearchLaboratories Inc., Suffolk, UK) for 1 hr. After subsequentwashing, the enzymatic reaction was conducted with 1-Step
Ultra TMB-ELISA (Pierce). After the reaction was stopped
with 1 M H2SO4, the optical density was measured at 450 nm
using an auto-plate reader. These reactions were performed
with a volume of 50 ␮L at room temperature.
Immunohistochemistry
Immunohistochemical staining was performed using theavidin-biotinylated immunoperoxidase method. In brief,
5-␮m sections were deparaffinized and rehydrated. All tissues
were then exposed to 3% hydrogen peroxidase for 5 min.
Then, K7508, its Fab fragment (K7508Fab), or rabbit anti-A
polyclonal antibody (Wako Pure Chemical Industries Ltd.)
was added to the sections for 30 min at room temperature.
Biotinylated secondary anti-mouse IgG (Dako) or anti-rabbit
IgG (Dako) was incubated for 30 min at room temperature
followed by the peroxidase-conjugated biotin-streptavidin
complex (Vectastain ABC Kit; Vector Laboratories Inc., Burlingame, CA) for 30 min at room temperature. Color wasdeveloped using 3,3-diaminobenzidine tetrahydrochloride
tablet sets (Dako) for 1 min. The sections were counterstainedwith Mayer’s hematoxylin.

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Transplantation • Volume 85, Number 3, February 15, 2008

Immunization of A431 Cells
The A-antigen-expressing cells, A431, were coated with K7508
or its Fab fragment for 30 min at 4°C. Mice were immunized byintraperitoneal injections of A-antigen-expressing cells mixed
with the Imject Alum (Pierce).
Statistical Analyses
Results are expressed as the mean ⫾ standard deviation. Student’s t test was used to determine significance among thegroups. A value of P⬍0.05 was considered significant.

RESULTS
Specificity Definition of a Novel Monoclonal
Antibody to the Blood Group A-Antigen
After generating a monoclonal antibody, K7508, to the bloodgroup A-antigen, we first characterized its specificity to theA-antigen by flow cytometric analysis. Both K7508 and its
Fab fragment (K7508Fab) demonstrated specificity for the
blood group A-antigen by strong binding with A-RBC (Figs.
1A and 1B) as well as A431, a cell line that expresses the bloodgroup A-antigen (Figs. 1G and 1H). Specificity of K7508 or
K7508Fab for the A-antigen was shown by the lack of reactivity with O-RBC (Figs. 1E and 1F) and weak reactivity with
B-RBC (Figs. 1C and 1D). The specificities of K7508 andK7508Fab were also characterized by ELISA (Fig. 2). The dataalso show that specificity is directed to the blood group Aantigen (trisaccharide) and not to the B- or O-antigens (tri- or
disaccharides, respectively). K7508 is of the IgG1 subclass (datanot shown). Immunostaining studies revealed that K7508 reacted strongly with RBCs and endothelia of capillaries and arteries of liver from a blood group A individual but did not react withthose tissues from B or O-individuals (Fig. 3).

FIGURE 5. Blood group A-antigen was masked using
K7508 or its Fab fragment (K7508Fab) in immunohistochemical analyses of liver tissues. Rabbit anti-A antibody
stained endothelial cells of liver (A). Either K7508 (B) or
K7508Fab (C) was added to the liver sections of a blood group-A
individual at a concentration of 100 ␮g/ml for 30 min at room
temperature. Then, 1/1000 diluted rabbit anti-A antibody wasreacted for 30 min. Biotinylated secondary anti-rabbit IgG wasincubated for 30 min at room temperature, followed by theperoxidase-conjugated biotin-streptavidin complex (Vectastain ABC Kit) for 30 min. Color was developed using
3,3-diaminobenzidine tetrahydrochloride for 1 min. The
sections were counterstained with Mayer’s hematoxylin.

Blood Group A-Antigen Neutralization by Anti-A
Antibody (K7508) in Vitro
We next investigated whether A-antigen on cells were neutralized by K7508 in flow cytometric analyses or immunohistochemistry. Results of flow cytometric analyses indicatedthat A-RBCs coated with K7508 were not detected by anotheranti-A antibody (A-IgM): A-antigen on A-RBCs was masked
by K7508 in vitro (Fig. 4A). In the same way, the reactivity of
A-IgM was diminished after A431 cells were coated with
K7508 (Fig. 4C). It was noteworthy that K7508Fab also inhibited A-IgM-binding to A-antigen on A-RBCs and A431 (Figs.
4B and 4D), indicating that K7508Fab had similar binding
activity to that of K7508 and masked A-antigen on the cells. In
immunohistochemistry, polyclonal anti-A antibodies recognized RBCs and endothelia of capillaries and arteries of bloodgroup-A liver (Fig. 5A). By contrast, the liver tissues coatedwith K7508 or K7508Fab were not stained by polyclonal rabbit anti-A antibody (Fig. 5B and 5C), indicating that Aantigen on the endothelia of the liver tissues was masked by
K7508 or K7508Fab. These results suggest that K7508 andK7508Fab masked A-antigen on tissues and might be usefulfor therapeutic use in vivo.
Suppression of Anti-A Antibody Production inMice by Neutralization of A-Antigen With K7508
or K7508Fab
We next investigated whether K7508 or K7508Fab suppress
the anti-A antibody production by neutralizing A-antigen in© 2008 Lippincott Williams & Wilkins

vivo. We first immunized mice with A431 cells after coatingwith K7508 by intraperitoneal injections. This in vivo model
might mimic organ transplantation because the A-antigen of
the donor graft induces the production of anti-A antibodies.
Flow cytometry (Fig. 6A) showed that sera from mice immunized by A431 coated with K7508 (S-A431-K7508) reacted to
A-RBCs more weakly than sera from mice immunized with
non-coated A431 (S-A431), suggesting that S-A431-K7508
contained a lower concentration of anti-A antibodies. These
results indicate that K7508 neutralizes A-antigen on A431
cells and that the production of mouse anti-A antibodies isinhibited in vivo. Furthermore, sera from mice immunizedby A431 coated with K7508Fab (S-A431-K7508Fab) reacted
weakly to A-RBCs (Fig. 6B), indicating that K7508Fab also
possesses neutralizing activity against A-antigen.
We next investigated the concentrations of mouseanti-A antibodies in S-A431-K7508, S-A431-K7508Fab, andS-A431 using ELISA with A-trisaccharides (Fig. 6C). The
concentration of anti-A antibodies increased gradually in S-

FIGURE 6. Neutralization of bloodgroup A-antigen on A431 cells using
K7508 and its Fab fragment (K7508Fab)in vivo. (A, B) Flowcytometric analyses
show that mice were immunized with
A431 cells coated with K7508 or
K7508Fab (bold lines), or noncoatedA431 cells (dark shadowed areas). The
A-RBCs were reacted with 1/10 diluted
sera from immunized mice as the firstantibody, followed by 1/1000 diluted
anti-mouse IgM-FITC as the secondary
antibody. Light shaded areas show
sera of mice without immunization as anegative control. (C) Five mice were
immunized twice (day 0 and day 7)
with A431 cells coated with K7508(squares), K7508Fab (triangles), or
non-coated A431 cells (circles). The
ELISA plate wells were coated with 1
␮g/ml A-trisaccharides. Then, 1/10 diluted immunized mice sera were usedas the first antibody; subsequently,
1/1000 diluted anti-mouse IgM-HRP
were used as the secondary antibody.
The enzymatic reaction was conductedwith a substrate solution containing
TMB. After the reaction was stopped
with 1 M H2SO4, the optical density wasmeasured at 450 nm using an autoplate reader. Data are the mean ⫾ SDof three independent experiments.
*P⬍0.01.

Hasegawa et al.

383

A431 for three weeks. In contrast, that of S-A431-K7508
slightly increased for one week, and then stopped increasingfrom one week to three weeks. Similarly, the concentration ofanti-A antibodies of S-A431-K7508Fab stopped increasing
after one week. These results suggest that A-antigen on A431
cells was neutralized by K7508 or K7508Fab.

DISCUSSION
In this study, we produced a novel antiblood group A
antibody, K7508, for developing a novel therapeutic strategy
for the ABO-incompatible organ transplantation. The major
barrier to ABO-incompatible organ transplantation is humoral rejection, which is known to be triggered by antigenantibody complex reaction (2, 5, 6). For that reason, thereduction of antibodies in plasma or the suppression of antibody production has been performed to overcome ABOincompatible transplantation (15–17). However, to date, thesuppression of blood group antigen has not been performed

384Transplantation • Volume 85, Number 3, February 15, 2008

clinically, probably because in vivo study about suppressionof blood group antigen is very difficult. To the best of ourknowledge, this study is the first one to use in vivo model
which mimics ABO-incompatible transplantation.
In vitro study, we performed neutralizing experiments
by K7508 using both A-antigen-expressing cells such as ARBC or A431 and human liver tissues. A-antigen-expressing
cells are used for application to in vivo study that mimics
ABO-incompatible transplantation; on the other hand, human liver tissues were used for discussing the clinical application. A-antigen on A-RBC or A431 were completely
masked by anti-A antibody, K7508 (Fig. 4), suggesting that
K7508 is also applicable to in vivo study: whether antibodies
against A-antigen-possessing graft are suppressed or not.
K7508 reacted with A-antigen stronger than other anti-A antibodies in ELISA (data not shown). Furthermore, we speculate that these anti-A antibodies recognize the similar epitopeof A-antigen; therefore other anti-A antibodies did not reactwith A-antigen after epitope of A-antigen was blocked by
K7508. Immunohistochemical analyses showed that Aantigen is highly expressed in endothelia of capillaries andarteries of blood group-A liver (Fig. 3). Importantly, K7508
completely blocked the reactivity of sequentially applied
other anti-A antibodies against endothelia of capillaries andarteries (Fig. 5). An in vivo study with the use of human livertissues is ethically difficult to perform; therefore, we moved
on to in vivo study using A-antigen-possessing cells.
The Fc portion of IgG is involved in antibody-dependentcell-mediated cytotoxicity and complement-dependent cell cytotoxicity. The classical pathway, which is one of complement
activation, is triggered by the binding of the complement
component C1q to the antigen-antibody complex. In the previous study, mouse RBCs coated in vitro with F(ab⬘)2 fragment of mouse RBC-specific antibody, when transfused into
mice, survived longer in circulation than RBCs coated withwhole IgG of mouse RBC-specific antibody (21). Therefore, we
prepared the Fab fragment of K7508 (K7508Fab) to prevent theantibody-dependent cell-mediated cytotoxicity or complementdependent cell cytotoxicity by K7508 for in vivo study. As shownin Figures 1–3, K7508Fab was also useful for flow cytometry,
ELISA, and immunohistochemistry. As shown in Figure 6, whenA-antigen-expressing cells were coated with K7508Fab, the production of anti-A antibody was also reduced in vivo. These findings suggest that A-antigen was neutralized by K7508Fab, andthat A-antigen lost its antigenecity. In vitro study, K7508Fab
completely blocked the reactivity of sequentially applied anotheranti-A antibodies against endothelia of capillaries and arteries(Fig. 5). Taken together, K7508Fab may be clinically applicablein ABO-incompatible organ transplantation.
Using A2 donors, who have less A-antigen than A1 donors, has brought success in ABO-incompatible liver transplantation and kidney transplantation (22–24). Fishbein et al.
reported that transplantation of blood group A2 livers intoblood group O recipients is safe and can be performed without graft loss and without regard to anti-A titer level (24).
They concluded that the transplantation of A2 livers into O
recipients can partially compensate for the more frequent useof O livers in recipients from other blood groups. Consequently, it is not necessary to neutralize blood group antigen
completely, and masking the part of blood group antigen
might turn around the outcome of ABO-incompatible trans-

plantation. Moreover, the feature of this method is the specific treatment against blood group antigen. Therefore, broad
and intensive immunosuppression, which causes severe infection and posttransplant lymphoproliferative disorder,might not be necessary (25, 26). In this study, we used only
anti-A-antigen antibodies; however, we are also planning to
produce anti-B-antigen antibodies, which may lead to a clinical use.
In conclusion, we produced a novel anti-A antibody:
K7508. Production of anti-A antibody was suppressed significantly in vivo when blood group A-antigen-expressing cells
were coated with K7508Fab. In the future, this neutralizing
procedure might become an effective strategy to control humoral rejection related to ABO-incompatible solid organtransplantation.
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The Transplantation Society Mission Statement
The Transplantation Society will provide the focus for global leadership intransplantation:
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development of the science and clinical practicescientific communication
continuing education
guidance on the ethical practiceThere are many benefits of being a part of TTS. Applying has never been so easy. Visit
the TTS website at www.transplantation-soc.org and apply today.