TY - JOUR
T1 - Production of anti-ABO blood group antibodies after minor ABO-incompatible bone marrow transplantation in NOD/SCID/gamma(c)(null) mice
AU - Tomita, Hirofumi
AU - Fuchimoto, Yasushi
AU - Mori, Takehiko
AU - Kato, Jun
AU - Uemura, Tomoe
AU - Handa, Makoto
AU - Tazawa, Hirofumi
AU - Ohdan, Hideki
AU - Okamoto, Shinichiro
AU - Kuroda, Tatsuo
PY - 2013/11
Y1 - 2013/11
N2 - ABO incompatibility is a barrier for solid organ transplantation, but not for hematopoietic stem cell transplantation. To investigate tolerance induction, we enrolled patients who had undergone minor ABO-incompatible (O into A group, n = 6) and ABO-identical (O into O group, n = 4) bone marrow transplantation (BMT). None of the six O into A patients were positive for recipient-specific (anti-blood group A) isohemagglutinins, whereas all four O into O patients were. Peripheral blood mononuclear cells (PBMCs) were engrafted into NOD/SCID/gamma(c)(null) (NOG) mice, followed by sensitization of blood group A red blood cells. Anti-blood group A antibodies (Abs) in the sera of the patients and the human PBMC-engrafted NOG mice were measured by enzyme-linked immunosorbent assays. Anti-blood group A Abs in the patients' sera were significantly correlated with anti-A isohemagglutinin titers (p < 0.01). In the human PBMC-engrafted NOG mice, anti-blood group A Abs were significantly lower in the O into A group than in the O into O group (p < 0.05), despite ex vivo restimulation of B cells. The results of this study suggest that long after receiving minor ABO-incompatible BMT, B cells derived from newly engrafted donor precursor cells were induced tolerance to recipient-specific antigens.
AB - ABO incompatibility is a barrier for solid organ transplantation, but not for hematopoietic stem cell transplantation. To investigate tolerance induction, we enrolled patients who had undergone minor ABO-incompatible (O into A group, n = 6) and ABO-identical (O into O group, n = 4) bone marrow transplantation (BMT). None of the six O into A patients were positive for recipient-specific (anti-blood group A) isohemagglutinins, whereas all four O into O patients were. Peripheral blood mononuclear cells (PBMCs) were engrafted into NOD/SCID/gamma(c)(null) (NOG) mice, followed by sensitization of blood group A red blood cells. Anti-blood group A antibodies (Abs) in the sera of the patients and the human PBMC-engrafted NOG mice were measured by enzyme-linked immunosorbent assays. Anti-blood group A Abs in the patients' sera were significantly correlated with anti-A isohemagglutinin titers (p < 0.01). In the human PBMC-engrafted NOG mice, anti-blood group A Abs were significantly lower in the O into A group than in the O into O group (p < 0.05), despite ex vivo restimulation of B cells. The results of this study suggest that long after receiving minor ABO-incompatible BMT, B cells derived from newly engrafted donor precursor cells were induced tolerance to recipient-specific antigens.
KW - Anti-ABO blood group antibodies
KW - B-cell tolerance
KW - Isohemagglutinins
KW - Minor ABO-incompatible bone marrow transplantation
KW - NOD/SCID/gamma(c)(null) mice
UR - http://www.scopus.com/inward/record.url?scp=84889090562&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84889090562&partnerID=8YFLogxK
U2 - 10.1111/ctr.12264
DO - 10.1111/ctr.12264
M3 - Article
C2 - 24125194
AN - SCOPUS:84889090562
VL - 27
SP - E702-E708
JO - Clinical Transplantation
JF - Clinical Transplantation
SN - 0902-0063
IS - 6
ER -