BACKGROUND: In contrast to human leukocyte antigen (HLA) matching, ABO-blood group incompatibility plays a minor role in the success of allogeneic hematopoietic stem cell transplantation (HSCT). Incompatible ABH histo-blood group antigens, expressed on recipient endothelial cells (EC) and donor erythroid progenitor cells, may represent targets for graft-versus-host disease (GVHD) and host-versus-graft reactions, respectively. The aims of the current study were to investigate: (1) red blood cell (RBC) engraftment and (2) EC chimerism as a potential result of replacement of recipient EC by donor bone marrow (BM)-derived EC in a patient following major ABO-incompatible (A to O) and gender-mismatched HSCT, who died at day 350 of severe acute GVHD. METHODS: Blood counts and anti-A/B isoagglutinin titers were analyzed repeatedly. Heart and BM specimens were obtained at autopsy. The expression of ABH histo-blood group antigens was examined by immunhistochemistry, X/Y chromosomes were detected by chromogen in situ hybridization (CISH). RESULTS: RBC engraftment defined as appearance of 1% reticulocytes in the peripheral blood was delayed and correlated with anti-donor isoagglutinin titers. Circulating hematopoietic cells were exclusively of donor origin demonstrating full donor hematopoietic chimerism, whereas EC in heart and BM blood vessels were exclusively of the recipient type. CONCLUSIONS: Pure red cell aplasia (PRCA) after major ABO-incompatible HSCT was caused by anti-A/B isoagglutinins produced by recipient-type plasma cells. Using ABO and gender mismatch for discrimination, heart and BM blood vessels demonstrated no evidence for EC chimerism 11 months after ABO-incompatible HSCT. These findings suggest that EC replacement and chimerism do not represent major mechanisms responsible for tolerance induction after HSCT.
BACKGROUND: In contrast to humanleukocyte antigen (HLA) matching, ABO-blood group incompatibility plays a minor role in the success of allogeneic hematopoietic stem cell transplantation (HSCT). Incompatible ABH histo-blood group antigens, expressed on recipient endothelial cells (EC) and donor erythroid progenitor cells, may represent targets for graft-versus-host disease (GVHD) and host-versus-graft reactions, respectively. The aims of the current study were to investigate: (1) red blood cell (RBC) engraftment and (2) EC chimerism as a potential result of replacement of recipient EC by donor bone marrow (BM)-derived EC in a patient following major ABO-incompatible (A to O) and gender-mismatched HSCT, who died at day 350 of severe acute GVHD. METHODS: Blood counts and anti-A/B isoagglutinin titers were analyzed repeatedly. Heart and BM specimens were obtained at autopsy. The expression of ABH histo-blood group antigens was examined by immunhistochemistry, X/Y chromosomes were detected by chromogen in situ hybridization (CISH). RESULTS: RBC engraftment defined as appearance of 1% reticulocytes in the peripheral blood was delayed and correlated with anti-donor isoagglutinin titers. Circulating hematopoietic cells were exclusively of donor origin demonstrating full donor hematopoietic chimerism, whereas EC in heart and BM blood vessels were exclusively of the recipient type. CONCLUSIONS: Pure red cell aplasia (PRCA) after major ABO-incompatible HSCT was caused by anti-A/B isoagglutinins produced by recipient-type plasma cells. Using ABO and gender mismatch for discrimination, heart and BM blood vessels demonstrated no evidence for EC chimerism 11 months after ABO-incompatible HSCT. These findings suggest that EC replacement and chimerism do not represent major mechanisms responsible for tolerance induction after HSCT.
Authors: Aaron C Logan; Zhiyu Wang; Kamran Alimoghaddam; Ruby M Wong; Tze Lai; Robert S Negrin; Carl Grumet; Brent R Logan; Mei-Jie Zhang; Stephen R Spellman; Stephanie J Lee; David B Miklos Journal: Biol Blood Marrow Transplant Date: 2015-01-05 Impact factor: 5.742