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Clin Transplant. 2013 Nov-Dec;27(6):E702-8. doi: 10.1111/ctr.12264. Epub 2013 Oct 11.

Production of anti-ABO blood group antibodies after minor ABO-incompatible bone marrow transplantation in NOD/SCID/gamma(c)(null) mice.

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Division of Pediatric Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan.


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.


B-cell tolerance; NOD/SCID/gamma(c)(null) mice; anti-ABO blood group antibodies; isohemagglutinins; minor ABO-incompatible bone marrow transplantation

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